@article{IBB_ID_54822, author={Roviello V, Gilhen-baker M, Vicidomini C, Roviello GN}, title={The Healing Power of Clean Rivers: In Silico Evaluation of the Antipsoriatic Potential of Apiin and Hyperoside Plant Metabolites Contained in River Waters}, date={2022 Feb 22}, journal={Int J Environ Res Public Health (ISSN: 1660-4601linking)}, year={2022}, fullvolume={23}, volume={23}, pages={2502--2510}, url={https://doi.org/10.3390/ijerph19052502}, abstract={ Humanity may benefit greatly from intact riverine ecosystems not only because they supply water to be used in the most common human activities, but also for the effects that clean rivers can have on human health. Herein, we used a computational approach to show that some phytochemicals produced by riparian plants as secondary metabolites, which are naturally released into river waters, can have therapeutic properties. These include antipsoriatic activities which we demonstrated in silico by modelling the interaction of apiin, guanosine and hyperoside, a few main river plant metabolites, with NF-kB, IL-17 and IL-36, which are recognized targets involved in psoriasis disease. In particular, we found that apiin and hyperoside are endowed with docking energies and binding affinities which are more favorable than the known reference inhibitors of the three protein targets whilst, in silico, guanosine shows comparable activity with respect to the inhibitors of IL-36 and NF-kB. The low skin permeation (logKp < −8) we predicted for apiin and hyperoside led us to hypothesize their possible utilization as topic antipsoriatic therapeutics, and in particular after PAINS (pan-assay interference compounds) score evaluation, we reached the conclusion that apiin, with no predicted tendency to react nonspecifically with the numerous targets involved in the biological cellular pathways, is particularly interesting for the desired therapeutic application. }, keywords={Environmental Health, Plant Metabolites, Phytomedicine, Anti-Psoriatic Drug, Molecular Docking, Ecosystem , Flavonoids , Guanosine , Humans , Nf-Kappa B , Quercetin Analogs, Derivatives , Rivers}, references={}, document_type={Research Journal Article}, affiliation={ Department of Chemical, Materials and Industrial Production Engineering (DICMaPI), University of Naples Federico II, Piazzale V. Tecchio 80, 80125 Naples, Italy }, ibbaffiliation={0}, } @article{IBB_ID_54821, author={Scognamiglio PL, Vicidomini C, Fontanella F, De Stefano C, Palumbo R, Roviello GN}, title={Protein binding of benzofuran derivatives: A CD spectroscopic and in silico comparative study of the effects of 4-nitrophenyl functionalized benzofurans and benzodifurans on BSA protein structure}, date={2022 Feb}, journal={Biomolecules}, year={2022}, fullvolume={29}, volume={29}, pages={262--273}, url={https://www.mdpi.com/journal/biomolecules/special_issues/protein_targeting_drug_discovery}, abstract={ Benzofuran derivatives are synthetic compounds that are finding an increasing interest in the scientific community not only as building blocks for the realization of new materials, but also as potential drugs thanks to their ability to interact with nucleic acids, interfere with the amyloid peptide aggregation and cancer cell cycle. However, their ability to interact with proteins is a theme still in need of investigation for the therapeutic importance that benzofurans could have in the modulation of protein-driven processes and for the possibility of making use of serum albumins as benzofurans delivery systems. To this scope, we investigated the protein binding ability of two 4-nitrophenyl functionalized benzofurans previously synthesized in our laboratory and herein indicated as BF1 and BDF1, which differed for the number of furan rings (a single moiety in BF1, two in BDF1), using bovine serum albumin (BSA) as model protein. By circular dichroism (CD) spectroscopy we demonstrated the ability of the two heteroaromatic compounds to alter the secondary structure of the serum albumin leading to different consequences in terms of BSA thermal stability with respect to the unbound protein (ΔT m > 3°C for BF1, -0.8°C for BDF1 with respect to unbound BSA, in PBS buffer, pH 7.5) as revealed in our CD melting studies. Moreover, a molecular docking study allowed us to compare the possible ligand binding modes of the mono and difuranic derivatives showing that while BF1 is preferentially housed in the interior of protein structure, BDF1 is predicted to bind the albumin surface with a lower affinity than BF1. Interestingly, the different affinity for the protein target predicted computationally was confirmed also experimentally by fluorescence spectroscopy (k D = 142.4 ± 64.6 nM for BDF1 vs. 28.4 ± 10.1 nM for BF1). Overall, the above findings suggest the ability of benzofurans to bind serum albumins that could act as their carriers in drug delivery applications. }, keywords={Serum Albumin, Benzofuran Ligands, Circular Dichroism, Fluorescence Titration, Molecular Docking, Protein-Ligand Interactions}, references={  Peters Jr, T., Serum albumin. Advances in protein chemistry 2. Carter, D. C.; Ho, J. X., Structure of serum albumin. 45, 153-203. Tatlidil, D.; Ucuncu, M.; Cakan-Akdogan, G., EPR studies of intermolecular interactions and competitive binding of drugs in a drug–BSA binding model. Physical Chemistry Chemical Physics 18, (32), 22531-22539. Mkrtchyan, A. F.; Saghyan, A. S.; Palumbo, R.; Belter, A.; Hayriyan, L. A.; Simonyan, H.; Roviello, V.; Roviello, G. N., Spectroscopic and SEM evidences for G4-DNA binding by a synthetic alkyne-containing amino acid with anticancer activity. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy macromolecule binding and anticancer activity of synthetic alkyne-containing l-phenylalanine derivatives. Structural relationship and binding mechanisms of five flavonoids with bovine serum albumin. Pospieszna-Markiewicz, I.; Mańka, M.; Insińska-Rak, M.; Dutkiewicz, G.; Patroniak, V.; Fik-Jaskółka, M. A., Synthesis and Spectroscopic Investigations of Schiff Base Ligand and Its Bimetallic Ag (I) Complex as DNA and BSA Binders. S.; Morimoto, M.; Saimoto, H., Guanidinylation of Chitooligosaccharides involving internal cyclization of the Guanidino group on the reducing end and effect of Guanidinylation on protein binding ability. Vakarov, S.; Meier-Menches, S. M.; Gerner, C.; Potocki, S.; Arion, V. B.; Gumienna-Kontecka, E.; Voloshin, Y.; Kovalska, V., Sensing of Proteins by ICD Response of Iron (II) Clathrochelates Functionalized by Carboxyalkylsulfide Groups. A.; Hamilton, J. A.; Curry, S., Location of high and low affinity fatty acid binding sites on human serum albumin revealed by NMR drug-competition analysis. Journal of molecular biology Mochizuki, S.; Noda, M.; Kobayashi, K., Crystal structure of human serum albumin at 2.5 Å resolution. Protein engineering Gomes, A.; Cavaco-Paulo, A., Albumin-based nanodevices as drug Current pharmaceutical design S. M.; Rudzińska, M.; Zamyatnin, A. A., Albumin nanovectors in cancer therapy and imaging. J. A.; Martínez-Tomé, M. J.; Esquembre, R.; Mateo, C. R., The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the D.; Cameron, I. L., A study of the molecular sources of nonideal osmotic pressure of bovine serum albumin solutions as a function of Biophysical journal Size-exclusion chromatography–multiangle laser light scattering analysis of β-lactoglobulin and bovine serum albumin in aqueous solution with added salt. Journal of Chromatography A 867, (1-2), 105-112. O'Konski, C. T., Hydrodynamic properties of bovine serum albumin monomer and dimer. Roller, P. P.; Fornace, A. J., Oligomerization of human Gadd45a Journal of Biological Chemistry Castello, P. R.; Flecha, F. L. G., Structural significance of the plasma membrane calcium pump oligomerization. membrane proteins. Current opinion in structural biology proteins against methylene chloride/water interface-induced denaturation and aggregation. Journal of Controlled Release Krumkacheva, O.; Mitin, D.; Suvorov, D.; Tormyshev, V.; Fedin, M.; Bowman, M. K.; Bagryanskaya, E., Reversible Dimerization of Human Behlke, J.; Billwitz, H.; BoHm, S.; Ebert, B.; Hamann, H.; Krumbiegel, J.; Lassmann, G., Temperature Behaviour of Human Serum European Journal of Biochemistry T.; Maruyama, T.; Otagiri, M., Pharmaceutical Aspects of the Recombinant Human Serum Albumin Dimer: Structural Characteristics, Biological Properties, and Medical Applications. Pharmaceutical Sciences 101, (9), 3033-3046. Mitchell, S.; Darrow, J.; Pippin, D., Privileged Structures: Applications in Drug Discovery. Combinatorial Chemistry & High Throughput Screening Amato, J.; Borbone, N.; Cerullo, V.; Hemminki, A.; Piccialli, V.; Zaccaria, S.; Mayol, L.; Piccialli, G., Synthesis and biological evaluation of unprecedented ring-expanded nucleosides (RENs) containing the imidazo[4,5-d][1,2,6]oxadiazepine ring system. Chemical Communications Borbone, N.; D’Errico, S.; Piccialli, G.; Mayol, L., Synthesis of N-1 and ribose modified inosine analogues on solid support. Tetrahedron Letters Temiz-Arpaci, Ö.; Yildiz, I.; Aki, E.; Özkan, S.; Kaynak, F., Synthesis, antimicrobial activity, pharmacophore analysis of some new 2-(substitutedphenyl/benzyl)-5-[(2-benzofuryl)carboxamido]benzoxazoles. Synthesis and antimicrobial evaluation of amide derivatives of benzodifuran-2-carboxylic acid. Khalilullah, M., Solvent-free microwave-assisted synthesis ofE-(1)-(6-benzoyl-3,5-dimethylfuro[3′,2′:4,5]benzo[b]furan-2-yl)-3-(aryl)-2-propen-1-ones and their antibacterial activity. Green Chemistry Letters and Klimko, P. G.; Hellberg, M. R.; May, J. A.; Kelly, C.; Williams, G.; McLaughlin, M. A.; Sharif, N. A., Novel benzodifuran analogs as potent 5-HT2A receptor agonists with ocular hypotensive activity. Bioorganic & Medicinal Chemistry Letters Grellier, P.; Dubois, J., Synthesis of polysubstituted benzofuran derivatives as novel inhibitors of parasitic growth. Medicinal Chemistry 21, (17), 4885-4892. Agatsuma, T.; Furukawa, H.; Naruto, S.; Sugano, Y., 4-Hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as potent anti-tumor agents. Lang, Q.; Tang, L.; Huang, Q.; Yu, L., In vitro and in vivo characterization of a benzofuran derivative, a potential anticancer agent, as a novel Aurora B kinase inhibitor. N.; Rigione, G.; Capasso, D.; Di Gaetano, S.; Riccardi, C.; Roviello, V.; Montesarchio, D., Benzodifuran Derivatives as Potential Antiproliferative Agents: Possible Correlation between Their Bioactivity and Aggregation Properties. W.-Z.; Xu, R.-M.; Gao, J.; Lu, A.-Q.; Xie, M.-P.; Li, L.; Zhang, J.-J.; Peng, Y.; Ma, L.-L.; Wang, X.-L.; Shi, J.-G.; Wang, S.-J., Bioactive Benzofuran Derivatives from Cortex Mori Radicis, and Their Neuroprotective and Analgesic Activities Mediated by mGluR1. V.; Musumeci, D.; Pedone, C., Synthesis of a novel benzodifuran derivative and its molecular recognition of poly rA RNA. Iannitti, R.; Palumbo, R.; La Manna, S.; Marasco, D.; Trifuoggi, M.; Diana, R.; Roviello, G. N., Evaluating the biological properties of synthetic 4-nitrophenyl functionalized benzofuran derivatives with telomeric DNA binding and antiproliferative activities. Roviello, G. N., Synthesis and nucleic acid binding evaluation of a thyminyl l-diaminobutanoic acid-based nucleopeptide. Haider, S.; Hoorelbeke, B.; Balzarini, J.; Piccialli, G., New anti-HIV aptamers based on tetra-end-linked DNA G-quadruplexes: effect of the base sequence on anti-HIV activity. Communications Pauw, E.; Gabelica, V., Hybridization of short complementary PNAs to G-quadruplex forming oligonucleotides: An electrospray mass spectrometry study. Pepe, A.; Oliviero, G.; Mayol, L.; Galeone, A., Effects of the introduction of inversion of polarity sites in the quadruplex forming oligonucleotide TGGGT. Bucci, M.; Vellecco, V.; Borbone, N.; Morelli, E.; Oliviero, G.; Novellino, E.; Piccialli, G.; Cirino, G.; Varra, M.; Fattorusso, C.; Mayol, L., Outstanding effects on antithrombin activity of modified TBA diastereomers containing an optically pure acyclic nucleotide Org. Biomol. Chem. 12, (28), 5235-5242. interactive fitting and simulation of protein circular dichroism spectra for use in education and for preliminary spectral analysis. arXiv preprint arXiv:2006.06275 spreadsheet program to simulate and analyze the far-UV circular dichroism spectra of proteins. Journal of Chemical Education Ikram, A.; Roviello, G. N., Novel insights on nucleopeptide binding: A spectroscopic and in silico investigation on the interaction of a thymine-bearing tetrapeptide with a homoadenine DNA. Molecular Liquids P. L.; Caruso, U.; Vicidomini, C.; Roviello, G. N., Evaluating In Silico the Potential Health and Environmental Benefits of Houseplant Volatile Organic Compounds for an Emerging ‘Indoor Forest Bathing’ International Journal of Environmental Research and N., Less COVID-19 deaths in southern and insular Italy explained by forest bathing, Mediterranean environment, and antiviral plant Roviello, G. N., In Silico Investigation on the Interaction of Chiral Phytochemicals from Opuntia ficus-indica with SARS-CoV-2 Mpro. Mokhir, A.; Roviello, G. N., Evidence of Protein Binding by a Nucleopeptide Based on a Thyminedecorated L-Diaminopropanoic Acid through CD and In Silico Studies. Current Medicinal Chemistry 28, (24), 5004-5015. Wolfson, H. J. In Efficient unbound docking of rigid molecules International workshop on algorithms in bioinformatics, 2002; Springer: pp 185-200. Inbar, Y.; Nussinov, R.; Wolfson, H. J., PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic acids research 33, (suppl_2), W363-W367. Wolfson, H. J., FireDock: fast interaction refinement in molecular Proteins: Structure, Function, and Bioinformatics C. N.; Ho, M. S., Annexin II Binds to Capsid Protein VP1 of Enterovirus 71 and Enhances Viral Infectivity. 85, (22), 11809-11820. Accurate prediction of inter-protein residue–residue contacts for homo-oligomeric protein complexes. Briefings in Bioinformatics L.; Bolz, S. N.; Kaiser, F.; Salentin, S.; Haupt, V. J.; Schroeder, M., PLIP 2021: Expanding the scope of the protein-ligand interaction profiler to DNA and RNA. Nucleic Acids Res Yang, L.; She, L.; Xing, R., Spectroscopic study on the effect of crystallization of the hydroxyapatite on the secondary structure of bovine serum albumin. Guang pu xue yu guang pu fen xi= Guang pu pH‐sensitive dispersion and debundling of single‐walled carbon nanotubes: lysozyme as a tool. Huang, X.; Wang, F.; Liu, S., Unfolding and refolding of bovine serum albumin induced by cetylpyridinium bromide. Jampour, S., Spectroscopic and molecular docking studies on interaction of two Schiff base complexes with bovine serum albumin. Journal of Biomolecular Structure and Dynamics }, document_type={Journal Article}, affiliation={ 1 Centerfor Advanced Biomaterial for Health Care (CABHC), Istituto Italianodi Tecnologia, I-80125 Naples, Italy;pasqualina.scognamiglio@iit.it 2 Istitutodi Biostrutture e Bioimmagini IBB-CNR; via Tommaso De Amicis 95,I-80145 Naples, Italy;  caterina.vicidomini@ibb.cnr.it; rosanna.palumbo@cnr.it ; giroviel@unina.it }, ibbaffiliation={1}, } @article{IBB_ID_54815, author={Roviello V, Scognamiglio PL, Caruso U, Vicidomini C, Roviello GN}, title={Evaluating In Silico the Potential Health and Environmental Benefits of Houseplant Volatile Organic Compounds for an Emerging 'Indoor Forest Bathing' Approach}, date={2022 Jan 16}, journal={Int J Environ Res Public Health (ISSN: 1660-4601linking)}, year={2022}, fullvolume={21}, volume={21}, pages={273--273}, url={https://www.mdpi.com/1660-4601/19/1/273/htm}, abstract={The practice of spending time in green areas to gain the health benefits provided by trees is well known, especially in Asia, as 'forest bathing', and the consequent protective and experimentally detectable effects on the human body have been linked to the biogenic volatile organic compounds released by plants. Houseplants are common in houses over the globe and are particularly appreciated for aesthetic reasons as well for their ability to purify air from some environmental volatile pollutants indoors. However, to the best of our knowledge, no attempt has been made to describe the health benefits achievable from houseplants thanks to the biogenic volatile organic compounds released, especially during the day, from some of them. Therefore, we performed the present study, based on both a literature analysis and in silico studies, to investigate whether the volatile compounds and aerosol constituents emitted by some of the most common houseplants (such as peace lily plant, Spathiphyllum wallisii, and iron plant, Aspidistra eliator) could be exploited in 'indoor forest bathing' approaches, as proposed here for the first time not only in private houses but also public spaces, such as offices, hospitals, and schools. By using molecular docking (MD) and other in silico methodologies for estimating vapor pressures and chemico-physical/pharmacokinetic properties prediction, we found that β-costol is an organic compound, emitted in appreciable amounts by the houseplant Spathiphyllum wallisii, endowed with potential antiviral properties as emerged by our MD calculations in a SARS-CoV-2 M(pro) (main protease) inhibition study, together with sesquirosefuran. Our studies suggest that the anti-COVID-19 potential of these houseplant-emitted compounds is comparable or even higher than known M(pro) inhibitors, such as eugenol, and sustain the utility of houseplants as indoor biogenic volatile organic compound emitters for immunity boosting and health protection.}, keywords={Air Pollutants, Analysis, Air Pollution, Indoor, Covid-19, Environmental Monitoring, Forests, Humans, Molecular Docking Simulation, Sars-Cov-2, Volatile Organic Compounds, Aspidistra Eliator, Spathiphyllum Wallisii, Biogenic Volatile Organic Compounds, Forest Bathing, Houseplant, Human Health, In Silico Analysis}, references={Furuyashiki, A.; Tabuchi, K.; Norikoshi, K.; Kobayashi, T.; Oriyama, S. A comparative study of the physiological and psychological effects of forest bathing (Shinrin-yoku) on working age people with and without depressive tendencies. Environ. Health Prev. Med. 2019 , 24 , 46. [ Google Scholar ] [ CrossRef ] [ PubMed ] Bielinis, E.; Takayama, N.; Boiko, S.; Omelan, A.; Bielinis, L. The effect of winter forest bathing on psychological relaxation of young Polish adults. Urban For. Urban Green. 2018 , 29 , 276–283. [ Google Scholar ] [ CrossRef ] Peterfalvi, A.; Meggyes, M.; Makszin, L.; Farkas, N.; Miko, E.; Miseta, A.; Szereday, L. Forest Bathing Always Makes Sense: Blood Pressure-Lowering and Immune System-Balancing Effects in Late Spring and Winter in Central Europe. Int. J. Environ. Res. Public Health 2021 , 18 , 2067. [ Google Scholar ] [ CrossRef ] [ PubMed ] Van den Berg, A.E. From Green Space to Green Prescriptions: Challenges and Opportunities for Research and Practice. Front. Psychol. 2017 , 8 , 268. [ Google Scholar ] [ CrossRef ] Antonelli, M.; Donelli, D.; Barbieri, G.; Valussi, M.; Maggini, V.; Firenzuoli, F. Forest Volatile Organic Compounds and Their Effects on Human Health: A State-of-the-Art Review. Int. J. Environ. Res. Public Health 2020 , 17 , 6506. [ Google Scholar ] [ CrossRef ] Roviello, V.; Roviello, G.N. Less COVID-19 deaths in southern and insular Italy explained by forest bathing, Mediterranean environment, and antiviral plant volatile organic compounds. Environ. Chem. Lett. 2021 , 1–11. [ Google Scholar ] [ CrossRef ] [ PubMed ] Roviello, V.; Gilhen-Baker, M.; Vicidomini, C.; Roviello, G.N. Forest-bathing and physical activity as weapons against COVID-19: A review. Environ. Chem. Lett. 2021 , 1–10. [ Google Scholar ] [ CrossRef ] [ PubMed ] Nieuwenhuis, M.; Knight, C.; Postmes, T.; Haslam, S.A. The relative benefits of green versus lean office space: Three field experiments. J. Exp. Psychol. Appl. 2014 , 20 , 199–214. [ Google Scholar ] [ CrossRef ] Kalantzis, A. The Impact of Indoor Plants on Well-Being in the Workplace. Ph.D. Thesis, University of the Witwatersrand, Faculty of Humanities, School of Human and Community Development, Johannesburg, South Africa, 2016. [ Google Scholar ] Kim, H.-H.; Yang, J.-Y.; Lee, J.-Y.; Park, J.-W.; Kim, K.-J.; Lim, B.-S.; Lee, G.-W.; Lee, S.-E.; Shin, D.-C.; Lim, Y.-W. House-plant placement for indoor air purification and health benefits on asthmatics. Environ. Health Toxicol. 2014 , 29 , e2014014. [ Google Scholar ] [ CrossRef ] Zhang, H.; Pennisi, S.V.; Kays, S.J.; Habteselassie, M.Y. Isolation and Identification of Toluene-Metabolizing Bacteria from Rhizospheres of Two Indoor Plants. Water Air Soil Pollut. 2013 , 224 , 1648. [ Google Scholar ] [ CrossRef ] Yang, D.S.; Son, K.-C.; Kays, S.J. Volatile Organic Compounds Emanating from Indoor Ornamental Plants. HortScience 2009 , 44 , 396–400. [ Google Scholar ] [ CrossRef ] Gubb, C.; Blanusa, T.; Griffiths, A.; Pfrang, C. Can houseplants improve indoor air quality by removing CO 2 and increasing relative humidity? Air Qual. Atmos. Health 2018 , 11 , 1191–1201. [ Google Scholar ] [ CrossRef ] Cummings, B.E.; Waring, M.S. Potted plants do not improve indoor air quality: A review and analysis of reported VOC removal efficiencies. J. Expo. Sci. Environ. Epidemiol. 2019 , 30 , 253–261. [ Google Scholar ] [ CrossRef ] Chang, L.-T.; Hong, G.-B.; Weng, S.-P.; Chuang, H.-C.; Chang, T.-Y.; Liu, C.-W.; Chuang, W.-Y.; Chuang, K.-J. Indoor ozone levels, houseplants and peak expiratory flow rates among healthy adults in Taipei, Taiwan. Environ. Int. 2019 , 122 , 231–236. [ Google Scholar ] [ CrossRef ] Abbass, O.A.; Sailor, D.J.; Gall, E.T. Effectiveness of indoor plants for passive removal of indoor ozone. Build. Environ. 2017 , 119 , 62–70. [ Google Scholar ] [ CrossRef ] Dudareva, N.; Pichersky, E.; Gershenzon, J. Biochemistry of plant volatiles. Plant Physiol. 2004 , 135 , 1893–1902. [ Google Scholar ] [ CrossRef ] Pichersky, E.; Noel, J.P.; Dudareva, N. Biosynthesis of plant volatiles: Nature’s diversity and ingenuity. Science 2006 , 311 , 808–811. [ Google Scholar ] [ CrossRef ] Kays, S.J.; Hatch, J.; Yang, D.S. Volatile floral chemistry of Heliotropium arborescens L. ‘Marine’. HortScience 2005 , 40 , 1237–1238. [ Google Scholar ] [ CrossRef ] Ciotti, M.; Ciccozzi, M.; Terrinoni, A.; Jiang, W.-C.; Wang, C.-B.; Bernardini, S. The COVID-19 pandemic. Crit. Rev. Clin. Lab. Sci. 2020 , 57 , 365–388. [ Google Scholar ] [ CrossRef ] [ PubMed ] Berman, H.M.; Battistuz, T.; Bhat, T.N.; Bluhm, W.F.; Bourne, P.E.; Burkhardt, K.; Feng, Z.; Gilliland, G.L.; Iype, L.; Jain, S.; et al. The Protein Data Bank. Acta Crystallogr. Sect. D Biol. Crystallogr. 2002 , 58 , 899–907. [ Google Scholar ] [ CrossRef ] Potemkin, V.; Potemkin, A.; Grishina, M. Internet Resources for Drug Discovery and Design. Curr. Top. Med. Chem. 2019 , 18 , 1955–1975. [ Google Scholar ] [ CrossRef ] [ PubMed ] Fik-Jaskółka, M.A.; Mkrtchyan, A.F.; Saghyan, A.S.; Palumbo, R.; Belter, A.; Hayriyan, L.A.; Simonyan, H.; Roviello, V.; Roviello, G.N. Biological macromolecule binding and anticancer activity of synthetic alkyne-containing l-phenylalanine derivatives. Amino Acids 2020 , 52 , 755–769. [ Google Scholar ] [ CrossRef ] [ PubMed ] Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 2009 , 31 , 455–461. [ Google Scholar ] [ CrossRef ] [ PubMed ] Umesh; Kundu, D.; Selvaraj, C.; Singh, S.K.; Dubey, V.K. Identification of new anti-nCoV drug chemical compounds from Indian spices exploiting SARS-CoV-2 main protease as target. J. Biomol. Struct. Dyn. 2020 , 39 , 3428–3434. [ Google Scholar ] Adasme, M.F.; Linnemann, K.L.; Bolz, S.N.; Kaiser, F.; Salentin, S.; Haupt, V.J.; Schroeder, M. PLIP 2021: Expanding the scope of the protein–ligand interaction profiler to DNA and RNA. Nucleic Acids 2021 , 49 , W530–W534. [ Google Scholar ] [ CrossRef ] Feng, Q.; Gao, Q.-Y.; Zhang, R.-M.; Gao, Y.; Hou, P. Constituent analysis of volatile organic compounds in three Liliaceae. J. Zhejiang AF Univ. 2011 , 28 , 513–518. [ Google Scholar ] A-jun, G.; Wang, Z.-Y. Inhibition of 9 Indoor Plants Against 4 Microorganism. North. Hortic. 2007 , 8 , 128–130. [ Google Scholar ] Lipinski, C.A. Lead- and drug-like compounds: The rule-of-five revolution. Drug Discov. Today Technol. 2004 , 1 , 337–341. [ Google Scholar ] [ CrossRef ] Rizzuti, B.; Ceballos-Laita, L.; Ortega-Alarcon, D.; Jimenez-Alesanco, A.; Vega, S.; Grande, F.; Conforti, F.; Abian, O.; Velazquez-Campoy, A. Sub-Micromolar Inhibition of SARS-CoV-2 3CLpro by Natural Compounds. Pharmaceuticals 2021 , 14 , 892. [ Google Scholar ] [ CrossRef ] [ PubMed ] Mancini, E.; De Martino, L.; Marandino, A.; Scognamiglio, M.R.; De Feo, V. Chemical Composition and Possible in Vitro Phytotoxic Activity of Helichrsyum italicum (Roth) Don ssp. italicum. Molecules 2011 , 16 , 7725–7735. [ Google Scholar ] [ CrossRef ] [ PubMed ] Dhinakaran, D.I.; Lipton, A.P. Bioactive compounds from Holothuria atra of Indian ocean. SpringerPlus 2014 , 3 , 673. [ Google Scholar ] [ CrossRef ] [ PubMed ] Sharbidre, A.; Dhage, P.; Duggal, H.; Meshram, R. In silico Investigation of Tridax procumbens Phyto-Constituents Against SARS-CoV-2 Infection. Biointerface Res. Appl. Chem. 2021 , 11 , 12120–12148. [ Google Scholar ] Hiremath, S.; Kumar, H.D.V.; Nandan, M.; Mantesh, M.; Shankarappa, K.S.; Venkataravanappa, V.; Basha, C.R.J.; Reddy, C.N.L. In silico docking analysis revealed the potential of phytochemicals present in Phyllanthus amarus and Andrographis paniculata, used in Ayurveda medicine in inhibiting SARS-CoV-2. 3 Biotech 2021 , 11 , 44. [ Google Scholar ] [ CrossRef ] Lambert, H.; Mohan, N.; Lee, T.-C. Ultrahigh binding affinity of a hydrocarbon guest inside cucurbit[7]uril enhanced by strong host–guest charge matching. Phys. Chem. Chem. Phys. 2019 , 21 , 14521–14529. [ Google Scholar ] [ CrossRef ] [ PubMed ] My, T.T.A.; Loan, H.T.P.; Hai, N.T.T.; Hieu, L.T.; Hoa, T.T.; Thuy, B.T.P.; Quang, D.T.; Triet, N.T.; Anh, T.T.V.; Dieu, N.T.X.; et al. Evaluation of the Inhibitory Activities of COVID-19 of Melaleuca cajuputi Oil Using Docking Simulation. ChemistrySelect 2020 , 5 , 6312–6320. [ Google Scholar ] [ CrossRef ] Llivisaca-Contreras, S.A.; Naranjo-Morán, J.; Pino-Acosta, A.; Pieters, L.; Vanden Berghe, W.; Manzano, P.; Vargas-Pérez, J.; León-Tamariz, F.; Cevallos-Cevallos, J.M. Plants and Natural Products with Activity against Various Types of Coronaviruses: A Review with Focus on SARS-CoV-2. Molecules 2021 , 26 , 4099. [ Google Scholar ] [ CrossRef ] Panikar, S.; Shoba, G.; Arun, M.; Sahayarayan, J.J.; Usha Raja Nanthini, A.; Chinnathambi, A.; Alharbi, S.A.; Nasif, O.; Kim, H.-J. Essential oils as an effective alternative for the treatment of COVID-19: Molecular interaction analysis of protease (Mpro) with pharmacokinetics and toxicological properties. J. Infect. Public Health 2021 , 14 , 601–610. [ Google Scholar ] [ CrossRef ] [ PubMed ] Asif, M.; Saleem, M.; Saadullah, M.; Yaseen, H.S.; Al Zarzour, R. COVID-19 and therapy with essential oils having antiviral, anti-inflammatory, and immunomodulatory properties. Inflammopharmacology 2020 , 28 , 1153–1161. [ Google Scholar ] [ CrossRef ] Li, Q. Effect of forest bathing trips on human immune function. Environ. Health Prev. Med. 2009 , 15 , 9–17. [ Google Scholar ] [ CrossRef ] [ PubMed ] Erickson, M.A.; Rhea, E.M.; Knopp, R.C.; Banks, W.A. Interactions of SARS-CoV-2 with the Blood–Brain Barrier. Int. J. Mol. Sci. 2021 , 22 , 2681. [ Google Scholar ] [ CrossRef ] [ PubMed ]}, document_type={Journal Article}, affiliation={Department of Chemical, Materials and Industrial Production Engineering (DICMaPI), University of Naples Federico II, Piazzale V. Tecchio 80, 80125 Naples, Italy., Center for Advanced Biomaterial for Health Care (CABHC), Istituto Italiano di Tecnologia, 80125 Naples, Italy., Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, 80126 Naples, Italy., Istituto di Biostrutture e Bioimmagini IBB-CNR, Via Tommaso De Amicis 95, 80145 Naples, Italy., }, ibbaffiliation={1}, } @article{IBB_ID_54849, author={Roviello V, Gilhen-baker M, Vicidomini C, Roviello GN}, title={Forest-bathing and physical activity as weapons against COVID-19: a review}, date={2022}, journal={Environ Chem Lett (ISSN: 1610-3653linking)}, year={2022}, fullvolume={6}, volume={6}, pages={131--140}, url={}, abstract={Strengthening the immune system in order to better withstand the threat of COVID-19 is an important way to ensure the protection of our health against the current pandemic associated with SARS-CoV-2. There are many ways to achieve this, but with current circumstances, certain modalities stand out as being the most valid and are certainly worth greater consideration. Here we review the effects that particular immuno-strengthening activities can have on limiting the severity of COVID-19 disease as well as preventing virus infection. Physical activity, in particular, should not be discounted as an important method of prevention of viral diseases as it triggers many biological processes within the human body which in turn lead to heightened natural defences against viral infections. When exercise is performed in forested areas, these protective health benefits may be increased since many plant species emit biogenic volatile compounds (VOCs) which, when inhaled, have many protective properties. These VOCs have been shown in particular to have immunostimulatory effects on the human body and, thus, they could be of use in the prevention and/or treatment of COVID-19. Being amongst trees may also help to alleviate stress and anxiety, lowering cortisol levels and consequently helping the proper functioning of the immune system. In the following work, we have performed an analysis of the available scientific literature which looks at the effects of physical exercise as well as 'forest-bathing' on the immune system's ability to fight disease, especially of course as it relates to COVID-19. Our review aims at shedding light on the benefits of exercising outdoors in green areas and suggests reforestation as a protective measure against future outbreaks.}, keywords={Body Immunity, Covid-19, Forest-Bathing, Physical Activity, Volatile Organic Compounds}, references={}, document_type={Journal Article, Review}, affiliation={Department of Chemical, Materials and Industrial Production Engineering (DICMaPI), University of Naples Federico II, Piazzale V. Tecchio 80, 80125 Naples, Italy. GRID: grid.4691.a. ISNI: 0000 0001 0790 385X Faculty of Physical Medicine and Rehabilitation, Georgian State Teaching University of Physical Education and Sport, 49, Chavchavadze avenue, 0162 Tbilisi, Georgia. Istituto di Biostrutture e Bioimmagini, IBB - CNR Mezzocannone Site and Headquarters, 80134 Naples, Italy. GRID: grid.429699.9. ISNI: 0000 0004 1790 0507}, ibbaffiliation={1}, } @article{IBB_ID_54644, author={Roviello V, Gilhen-baker M, Vicidomini C, Roviello GN}, title={Forest-bathing and physical activity as weapons against COVID-19: a review}, date={2021 Oct}, journal={Environ Chem Lett (ISSN: 1610-3653linking)}, year={2021}, fullvolume={11}, volume={11}, pages={1--10}, url={https://rdcu.be/cycin}, abstract={Strengthening the immune system in order to better withstand the threat of COVID-19 is an important way to ensure the protection of our health against the current pandemic associated with SARS-CoV-2. There are many ways to achieve this, but with current circumstances, certain modalities stand out as being the most valid and are certainly worth greater consideration. Here we review the efects that particular immuno-strengthening activities can have on limiting the severity of COVID-19 disease as well as preventing virus infection. Physical activity, in particular, should not be discounted as an important method of prevention of viral diseases as it triggers many biological processes within the human body which in turn lead to heightened natural defences against viral infections. When exercise is performed in forested areas, these protective health benefts may be increased since many plant species emit biogenic volatile compounds (VOCs) which, when inhaled, have many protective properties. These VOCs have been shown in particular to have immunostimulatory efects on the human body and, thus, they could be of use in the prevention and/or treatment of COVID-19. Being amongst trees may also help to alleviate stress and anxiety, lowering cortisol levels and consequently helping the proper functioning of the immune system. In the following work, we have performed an analysis of the available scientifc literature which looks at the efects of physical exercise as well as ‘forest-bathing’ on the immune system’s ability to fght disease, especially of course as it relates to COVID-19. Our review aims at shedding light on the benefts of exercising outdoors in green areas and suggests reforestation as a protective measure against future outbreaks.}, keywords={Covid-19, Body Immunity, Physical Activity, Forest-Bathing, Volatile Organic Compounds}, references={ Alyammahi SK, Abdin SM, Alhamad DW, Elgendy SM, Altell AT, Omar HA (2021) The dynamic association between COVID-19 and chronic disorders: An updated insight into prevalence, mechanisms and therapeutic modalities. Infect Genet Evol 87:104647.  https://doi.org/10.1016/j.meegid.2020.104647 Ammar A, Brach M, Trabelsi K, Chtourou H, Boukhris O, Masmoudi L, Bouaziz B et al (2020) Effects of COVID-19 Home Confinement on Eating Behaviour and Physical Activity: Results of the ECLB-COVID19 International Online Survey. Nutrients 12(6)  https://www.mdpi.com/2072-6643/12/6/1583#cite }, document_type={Review Journal Article}, affiliation={* Giovanni N. Roviellogiroviel@unina.it1 Department of Chemical, Materials and IndustrialProduction Engineering (DICMaPI), University of NaplesFederico II, Piazzale V. Tecchio 80, 80125 Naples, Italy2 Faculty of Physical Medicine and Rehabilitation, GeorgianState Teaching University of Physical Education and Sport,49, Chavchavadze avenue, 0162 Tbilisi, Georgia3 Istituto di Biostrutture e Bioimmagini, IBB - CNRMezzocannone Site and Headquarters, 80134 Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_54635, author={Vicidomini C, Roviello V, Roviello GN}, title={In Silico Investigation on the Interaction of Chiral Phytochemicals from Opuntia ficus-indica with SARS-CoV-2 Mpro}, date={2021 Jul}, journal={Symmetry}, year={2021}, fullvolume={10}, volume={10}, pages={1041--1048}, url={https://doi.org/10.3390/sym13061041}, abstract={Opuntia ficus-indica is a cactaceous plant native to America but, nowadays, widely found worldwide, having been the most common domesticated species of cactus grown as a crop plant in semiarid and arid parts of the globe, including several Mediterranean basin countries. Opuntia ficus-indica can be regarded as a medicinal plant, being source of numerous bioactive phytochemicals such as vitamins, polyphenols, and amino acids. The urgent need for therapeutic treatments for the COronaVIrus Disease 19 (COVID-19), caused by the Severe Acute Respiratory Syndrome (SARS)-Coronavirus (CoV)-2, justifies the great attention currently being paid not only to repurposed antiviral drugs, but also to natural products and herbal medications. In this context, the anti-COVID-19 utility of Opuntia ficus-indica as source of potential antiviral drugs was investigated in this work on the basis of the activity of some of its phytochemical constituents. The antiviral potential was evaluated in silico in docking experiments with Mpro, i.e., the main protease of SARS-CoV-2, that is one of the most investigated protein targets of therapeutic strategies for COVID-19. By using two web-based molecular docking programs (1-Click Mcule and COVID-19 Docking Server), we found, for several flavonols and flavonol glucosides isolated from Opuntia ficus-indica, good binding affinities for Mpro, and in particular, binding energies lower than −7.0 kcal/mol were predicted for astragalin, isorhamnetin, isorhamnetin 3-O-glucoside, 3-O-caffeoyl quinic acid, and quercetin 5,4′-dimethyl ether. Among these compounds, the chiral compound astragalin showed in our in silico studies the highest affinity for Mpro (−8.7 kcal/mol) and also a low toxicity profile, emerging, thus, as an interesting protease inhibitor candidate for anti-COVID-19 strategies.}, keywords={Plant Drugs, Opuntia Ficus-Indica, Sars-Cov-2, Covid-19, Docking, Energy Minimization, Pandemic, Therapeutic}, references={}, document_type={Research Journal Article}, affiliation={ by  Caterina Vicidomini  1,† , }, ibbaffiliation={1}, } @article{IBB_ID_54562, author={Vicidomini C, Roviello V, Roviello GN}, title={Molecular Basis of the Therapeutical Potential of Clove (Syzygium aromaticum L. ) and Clues to Its Anti-COVID-19 Utility}, date={2021 Mar 26}, journal={Molecules (ISSN: 1420-3049linking, 1420-3049electronic)}, year={2021}, fullvolume={52}, volume={52}, pages={1880--1886}, url={https://www.mdpi.com/1420-3049/26/7/1880/htm}, abstract={The current COronaVIrus Disease 19 (COVID-19) pandemic caused by SARS-CoV-2 infection is enormously affecting the worldwide health and economy. In the wait for an effective global immunization, the development of a specific therapeutic protocol to treat COVID-19 patients is clearly necessary as a short-term solution of the problem. Drug repurposing and herbal medicine represent two of the most explored strategies for an anti-COVID-19 drug discovery. Clove (Syzygium aromaticum L.) is a well-known culinary spice that has been used for centuries in folk medicine in many disorders. Interestingly, traditional medicines have used clove since ancient times to treat respiratory ailments, whilst clove ingredients show antiviral and anti-inflammatory properties. Other interesting features are the clove antithrombotic, immunostimulatory, and antibacterial effects. Thus, in this review, we discuss the potential role of clove in the frame of anti-COVID-19 therapy, focusing on the antiviral, anti-inflammatory, and antithrombotic effects of clove and its molecular constituents described in the scientific literature.}, keywords={Coronavirus Infections, Pandemics, Natural Compounds, Clove, Syzygium Aromaticum, Eugenol, Eugeniin, Sars-Cov-2, Covid-19, Phytochemicals, Herbal Medicine, Adjuvants, Immunologic Chemistry Pharmacology, Anti-Inflammatory Agents, Non-Steroidal Chemistry Pharmacology, Antiviral Agents Chemistry Pharmacology, Covid-19 Drug Therapy Prevention, Control, Fibrinolytic Agents Pharmacology, Herbal Medicine Methods, Humans, Phytochemicals Chemistry Pharmacology, Plants, Medicinal Chemistry, Syzygium Chemistry}, references={}, document_type={Review Journal Article}, affiliation={ 1 }, ibbaffiliation={1}, } @article{IBB_ID_54397, author={Marasco D, Vicidomini C, Krupa P, Cioffi F, Pham DQH, Li MS, Florio D, Broersen K, De Pandis MF, Roviello GN}, title={Plant isoquinoline alkaloids as potential neurodrugs: A comparative study of the effects of benzo[c]phenanthridine and berberine based compounds on β-amyloid aggregation}, date={2021 Jan 25}, journal={Chem Biol Interact (ISSN: 0009-2797linking)}, year={2021}, fullvolume={130}, volume={130}, pages={109300--109301}, url={https://doi.org/10.1016/j.cbi.2020.109300}, abstract={Herein we present a comparative study of the effects of isoquinoline alkaloids belonging to benzo[c]phenanthridine and berberine families on β-amyloid aggregation. Results obtained using a Thioflavine T (ThT) fluorescence assay and circular dichroism (CD) spectroscopy suggested that the benzo[c]phenanthridine nucleus, present in both sanguinarine and chelerythrine molecules, was directly involved in an inhibitory effect of Aβ(1-42) aggregation. Conversely, coralyne, that contains the isomeric berberine nucleus, significantly increased propensity for Aβ(1-42) to aggregate. Surface Plasmon Resonance (SPR) experiments provided quantitative estimation of these interactions: coralyne bound to Aβ(1-42) with an affinity (K(D) = 11.6 μM) higher than benzo[c]phenanthridines. Molecular docking studies confirmed that all three compounds are able to recognize Aβ(1-42) in different aggregation forms suggesting their effective capacity to modulate the Aβ(1-42) self-recognition mechanism. Molecular dynamics simulations indicated that coralyne increased the β-content of Aβ(1-42), in early stages of aggregation, consistent with fluorescence-based promotion of the Aβ(1-42) self-recognition mechanism by this alkaloid. At the same time, sanguinarine induced Aβ(1-42) helical conformation corroborating its ability to delay aggregation as experimentally proved in vitro. The investigated compounds were shown to interfere with aggregation of Aβ(1-42) demonstrating their potential as starting leads for the development of therapeutic strategies in neurodegenerative diseases.}, keywords={Amyloid Beta, Neurodrug, Amyloid Aggregation, Natural Products, Chelerythrine, Sanguinarine, Coralyne, Berberine, Alzheimer, S Disease, Alkaloids Pharmacology, Amyloid Beta-Peptides Metabolism, Benzophenanthridines Pharmacology, Berberine Pharmacology, Berberine Alkaloids Pharmacology, Humans, Isoquinolines Pharmacology, Molecular Docking Simulation, Neuroprotective Agents Pharmacology, Plants Chemistry, Protein Aggregates Drug Effects}, references={}, document_type={Research Journal Article, Comparative Study}, affiliation={Department of Pharmacy, University of Naples Federico II, Via Mezzocannone 16, 80134, Naples, Italy Istituto di Biostrutture e Bioimmagini IBB - CNR, Via Mezzocannone 16, I-80134 Naples, Italy. Institute of Physics Polish Academy of Sciences, Al. Lotników 32/46, 02-668, Warsaw, Poland. Nanobiophysics Group, Technical Medical Centre, Faculty of Science and Technology, University of Twente, Enschede, the Netherlands. Institute for Computational Sciences and Technology, SBI building, Quang Trung Software City, Tan ChanhHiep Ward, District 12, Ho Chi Minh City, Viet Nam. Applied Stem Cell Technologies, Technical Medical Centre, Faculty of Science and Technology, University of Twente, Enschede, the Netherlands. San Raffaele Cassino Institute, San Raffaele SPA, 03043, Cassino, FR, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_53934, author={Vicidomini C, Cioffi F, Broersen K, Roviello V, Riccardi C, Montesarchio D, Capasso D, Gaetano SD, Musumeci D, Roviello GN}, title={Benzodifurans for biomedical applications: BZ4, a selective anti-proliferative and anti-amyloid lead compound}, date={2019 Feb 25}, journal={Future Med Chem (ISSN: 1756-8919linking, 1756-8927electronic)}, year={2019}, fullvolume={544}, volume={544}, pages={285--302}, url={https://www.future-science.com/doi/full/10.4155/fmc-2018-0473}, abstract={AIM: Our goal is to evaluate benzodifuran-based scaffolds for biomedical applications. METHODOLOGY: We here explored the anticancer and anti-amyloid activities of a novel compound (BZ4) in comparison with other known benzodifuran analogs, previously studied in our group, and we have explored its ability to interact with different DNA model systems. RESULTS: BZ4 shows antiproliferative activity on different cancer cells; does not affect noncancerous control cells and alters the aggregation properties of beta-amyloid, as ascertained by circular dichroism, fluorescence spectroscopy and scanning electron microscopy analysis. An overall, qualitative picture on the mechanistic aspects related to the biological activities is discussed in light of the dynamic light scattering, UV, circular dichroism and fluorescence data, as well as of the metal ion-binding properties of BZ4.}, keywords={Anti-Amyloid, Anticancer, Synthesis, }, references={}, document_type={Research Journal Article, }, affiliation={CNR, Institute of Biostructure & Bioimaging, Via Mezzocannone site & Headquarters, 80134 Naples, Italy. Nanobiophysics, Faculty of Science & Technology (TNW), Technical Medical Centre, University of Twente, The Netherlands. Advanced Metrologic Service Center (CeSMA), University of Naples Federico II, Corso N. Protopisani, 80146 Naples, Italy. Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, 80126 Naples, Italy. Department of Pharmacy, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_53809, author={Galli M, Vicidomini C, Rozin Kleiner AF, Vacca L, Cimolin V, Condoluci C, Stocchi F, De Pandis MF}, title={Peripheral neurostimulation breaks the shuffling steps patterns in Parkinsonian gait: a double blind randomized longitudinal study with Automated Mechanical Peripheral Stimulation}, date={2018 Dec}, journal={Eur J Phys Rehabil Med (ISSN: 1973-9087linking)}, year={2018}, fullvolume={239}, volume={239}, pages={860--865}, url={}, abstract={ BACKGROUND: The shuffling steps pattern is a typical feature of gait in patients affected by Parkinson's Disease (PD), which progressively reduces their quality of life, being related to the risk of falls in this population. Recently, Automated Mechanical Peripheral Stimulation (AMPS) was presented as an integrative rehabilitative treatment based on peripheral stimulation able to improve the gait spatiotemporal parameters in PD patients. AIM: To evaluate the effects of AMPS on shuffling steps pattern by analyzing the kinematic and spatio-temporal gait parameters. DESIGN: Double blind randomized longitudinal study. SETTING: Outpatients. POPULATION: PD patients. METHODS: In this double blind randomized longitudinal study, 14 patients with PD were treated with effective-AMPS (AMPS Group), while 14 PD patients were treated with placebo-AMPS (SHAM Group); 32 healthy subjects were deemed the control group (CG). A dedicated medical device (GondolaTM Medical Technologies, Switzerland) was used to deliver both stimulations. Each treatment session lasted about 15 minutes, including preparation (approx. 10 to 13 minutes) and stimulation (approx. 2 minutes). All PD patients were given six AMPS/SHAM treatments sessions, twice a week, delivered during the off-levodopa phase, having withdrawn from dopaminergic medication overnight. We evaluated spatio-temporal and kinematic variables of gait with quantitative 3D-Gait Analysis as follows: before and after the first intervention (acute phase), then after the sixth session (long term phase). RESULTS: We detected differences in all gait variables immediately after the first session of AMPS treatment and again after the sixth stimulation session. CONCLUSIONS: AMPS treatment changes the shuffling steps pattern that is typical of PD subjects, increasing the ROM of hip, knee and ankle joints during the gait cycle. CLINICAL REHABILITATION IMPACT: This data present further evidence that a rehabilitative approach based on the AMPS treatment can induce improvements in the gait pattern of patients affected by PD. }, keywords={Aged , Double-Blind Method , Electric Stimulation Therapy Methods , Female , Gait Disorders, Neurologic Etiology Physiopathology Therapy , Humans , Longitudinal Studies , Middle Aged , Parkinson Disease Complications Physiopathology Rehabilitation , Range Of Motion, Articular , Treatment Outcome , Walking Speed, }, references={}, document_type={Journal Article, Randomized Controlled Trial, }, affiliation={Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy - manuela.galli@polimi.it. Biostructure and Bioimaging Institute (IBB), National Research Council (CNR), Naples, Italy. San Raffaele Cassino Hospital, Tosinvest Sanità, Cassino, Italy. Casa Cura Policlinico (CCP), Milan, Italy. IRCCS San Raffaele Pisana, Tosinvest Sanità, Rome, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_53469, author={Roviello GN, Iannitti R, Palumbo R, Simonyan H, Vicidomini C, Roviello V}, title={Lac-L-TTA, a novel lactose-based amino acid-sugar conjugate for anti-metastatic applications}, date={2017 May 06}, journal={Amino Acids (ISSN: 0939-4451, 1438-2199, 1438-2199electronic)}, year={2017}, fullvolume={304}, volume={304}, pages={1347--1353}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85018773735&doi=10.1007%2fs00726-017-2433-2&partnerID=40&md5=4d278d56fb94253f6dc512cd4be5fc8e}, abstract={Abstract: Here we describe the synthesis, chromatographic purification, MS and NMR characterization of a new lactosyl-derivative, i.e. a lactosyl thiophenyl-substituted triazolyl-thione l-alanine (Lac-L-TTA). This amino acid–sugar conjugate was prepared by solution synthesis in analogy to the natural fructosyl-amino acids. Furthermore, we investigated the inhibition of PC-3 prostate cancer cell colony formation by this lactose derivative in comparison with the less polar fructose-based derivative, Fru-L-TTA. This let us to compare the properties of the artificial derivative, object of the present work, with the monosaccharide-based counterpart and to obtain a preliminary information on the influence of polarity on such biological activity. A significantly higher anticancer effect of Lac-L-TTA with respect to the fructose analogue emerged from our study suggesting that the anti-metastatic potential of fructosyl-amino acids can be enhanced by increasing the polarity of the compounds, for example by introducing disaccharide moieties in place of fructose. © 2017, Springer-Verlag Wien.}, keywords={Anti-Metastatic, Fructosyl-Amino Acid, Glycated Amino Acid, Lactose, Antimetastatic Agent, Antineoplastic Agent, Fructosyl Thiophenyl Substituted Triazolyl Thione Alanine, Lactosyl Thiophenyl Substituted Triazolyl Thione Alanine, Unclassified Drug, Carbohydrate, Lac-L-Tta, Article, Cancer Chemotherapy, Cancer Inhibition, Concentration Response, Controlled Study, Drug Mechanism, Drug Purification, Drug Synthesis, Human, Human Cell, Mass Spectrometry, Metastasis Inhibition, Priority Journal, Prostate Cancer, Proton Nuclear Magnetic Resonance, Cell Proliferation, Cfu Counting, Chemistry, Drug Effects, Pathology, Prostate Tumor, Tumor Cell Culture, Colony-Forming Units Assay, Neoplasm Metastasis, Prostatic Neoplasms, Sugars, }, references={Campo, V.L., Carvalho, I., Allman, S., Davis, B.G., Field, R.A., Chemical and chemoenzymatic synthesis of glycosyl-amino acids and glycopeptides related to Trypanosoma cruzi mucins (2007) Org Biomol Chem, 5, pp. 2645-2657. , COI: 1:CAS:528:DC%2BD2sXosVShtLg%3D, PID: 1801954 Di Fabio, G., De Capua, A., De Napoli, L., Montesarchio, D., Piccialli, G., Rossi, F., Benedetti, E., A new strategy for the solid-phase synthesis of glycoconjugate biomolecules (2001) Synlett, 3, pp. 341-344 Esposito, G., Teta, R., Miceli, R., Ceccarelli, L.S., Della Sala, G., Camerlingo, R., Irollo, E., Costantino, V., Isolation and assessment of the in vitro anti-tumor activity of smenothiazole A and B, chlorinated thiazole containing peptide/polyketides from the Caribbean sponge, Smenospongia aurea (2015) Mar Drugs, 13, pp. 444-459. , PID: 25603342 Estendorfer, S., Ledl, F., Severin, T., Formation of an aminoreductone from glucose (1990) Angew Chem Int Ed Engl, 29, pp. 536-537 Gallas, K., Pototschnig, G., Adanitsch, F., Stütz, A.E., Wrodnigg, T.M., The Amadori rearrangement as glycoconjugation method: synthesis of non-natural C-glycosyl type glycoconjugates (2012) Beilstein J Org Chem, 8, pp. 1619-1629. , COI: 1:CAS:528:DC%2BC38XhsFSitLfK, PID: 23209494 Glinsky, G.V., Price, J.E., Glinsky, V.V., Mossine, V.V., Kiriakova, G., Metcalf, J.B., Inhibition of human breast cancer metastasis in nude mice by synthetic glycoamines (1996) Cancer Res, 56, pp. 5319-5324. , COI: 1:CAS:528:DyaK28Xntl2mtr8%3D, PID: 8968076 Gruner, S.A.W., Locardi, E., Lohof, E., Kessler, H., Carbohydrate-based mimetics in drug design: sugar amino acids and carbohydrate scaffolds (2002) Chem Rev, 102, pp. 491-514. , COI: 1:CAS:528:DC%2BD38XotVylug%3D%3D, PID: 11841252 Horikawa, H., Okada, M., Nakamura, Y., Sato, A., Iwamoto, N., Production of hydroxyl radicals and α-dicarbonyl compounds associated with Amadori compound-Cu 2 complex degradation (2002) Free Radic Res, 36, pp. 1059-1065. , COI: 1:CAS:528:DC%2BD38Xos1agsLg%3D, PID: 12516876 Jemal, A., Bray, F., Center, M.M., Ferlay, J., Ward, E., Forman, D., Global cancer statistics (2011) CA Cancer J Clin, 61, pp. 69-90. , PID: 21296855 Kumar, V., Ramesh, N.G., A versatile strategy for the synthesis of N-linked glycoamino acids from glycals (2007) Org Biomol Chem, 5, pp. 3847-3858. , COI: 1:CAS:528:DC%2BD2sXhtlSmur%2FN, PID: 18004466 Mehlen, P., Puisieux, A., Metastasis: a question of life or death (2006) Nat Rev Cancer, 6, pp. 449-458. , COI: 1:CAS:528:DC%2BD28XkvVyltrY%3D, PID: 16723991 Mossine, V.V., Chopra, P., Mawhinney, T.P., Interaction of tomato lycopene and ketosamine against rat prostate tumorigenesis (2008) Can Res, 68, pp. 4384-4391. , COI: 1:CAS:528:DC%2BD1cXmsFKmu70%3D Mottram, D.S., Flavor compounds formed during the Maillard reaction: thermally generated flavors (1994) Maillard Microw Extrus Process, 543, pp. 104-126. , COI: 1:CAS:528:DyaK2cXhtVGiurY%3D Rakosi, K., Szolomajer-Csikos, O., Kalmar, L., Szurmai, Z., Kerekgyarto, J., Toth, G.K., Synthesis of N-glycopeptides applying glycoamino acid building blocks with a combined Fmoc/Boc strategy (2011) Protein Pept Lett, 18, pp. 679-683. , COI: 1:CAS:528:DC%2BC3MXnvVGrurc%3D, PID: 21342098 Risseeuw, M.D., Overhand, M., Fleet, G.W., Simone, M.I., A compendium of sugar amino acids (SAA): scaffolds, peptide- and glyco-mimetics (2007) Tetrahedron Asymmetry, 18, pp. 2001-2010. , COI: 1:CAS:528:DC%2BD2sXhtFSiur7P Roviello, G.N., Moccia, M., Sapio, R., Valente, M., Bucci, E.M., Castiglione, M., Pedone, C., Musumeci, D., Synthesis, characterization and hybridization studies of new nucleo-γ-peptides based on diaminobutyric acid (2006) J Pept Sci, 12, pp. 829-835. , COI: 1:CAS:528:DC%2BD2sXktFar, PID: 17131297 Roviello, G.N., Musumeci, D., Moccia, M., Castiglione, M., Sapio, R., Valente, M., Bucci, E.M., Pedone, C., dabPNA: design, synthesis, and DNA binding studies (2007) Nucleosides Nucleotides Nucleic Acids, 26, pp. 1307-1310. , COI: 1:CAS:528:DC%2BD2sXhtl2hurnJ, PID: 18066773 Roviello, G.N., Benedetti, E., Pedone, C., Bucci, E.M., Nucleobase-containing peptides: an overview of their characteristic features and applications (2010) Amino Acids, 39, pp. 45-57. , COI: 1:CAS:528:DC%2BC3cXntVert7o%3D, PID: 20349320 Roviello, G.N., Gaetano, S.D., Capasso, D., Franco, S., Crescenzo, C., Bucci, E.M., Pedone, C., RNA-binding and viral reverse transcriptase inhibitory activity of a novel cationic diamino acid-based peptide (2011) J Med Chem, 54, pp. 2095-2101. , COI: 1:CAS:528:DC%2BC3MXivFyhsrg%3D, PID: 21391685 Roviello, G.N., Vicidomini, C., Di Gaetano, S., Capasso, D., Musumeci, D., Roviello, V., Solid phase synthesis and RNA-binding activity of an arginine-containing nucleopeptide (2016) RSC Adv., 6, pp. 14140-14148. , COI: 1:CAS:528:DC%2BC28Xhtl2qt70%3D Roviello, G.N., Roviello, V., Autiero, I., Saviano, M., Solid phase synthesis of TyrT, a thymine–tyrosine conjugate with poly(A) RNA-binding ability (2016) RSC Adv., 6, pp. 27607-27613. , COI: 1:CAS:528:DC%2BC28XjsVehsrs%3D Roviello, G.N., Iannitti, R., Roviello, V., Palumbo, R., Simonyan, H., Vicidomini, C., Synthesis and biological evaluation of a novel Amadori compound (2017) Amino Acids Russo, A., Aiello, C., Grieco, P., Marasco, D., Targeting “Undruggable” proteins: design of synthetic cyclopeptides (2016) Curr Med Chem, 23, pp. 748-762. , COI: 1:CAS:528:DC%2BC28Xlt1KjtL0%3D, PID: 26758797 Saghyan, A.S., Simonyan, H.M., Petrosyan, S.G., Geolchanyan, A.V., Roviello, G.N., Musumeci, D., Roviello, V., Thiophenyl-substituted triazolyl-thione l-alanine: asymmetric synthesis, aggregation and biological properties (2014) Amino Acids, 46, pp. 2325-2332. , COI: 1:CAS:528:DC%2BC2cXhtVaju7jI, PID: 24952728 Tai, S., Sun, Y., Squires, J.M., Zhang, H., Oh, W.K., Liang, C.-Z., Huang, J., PC3 is a cell line characteristic of prostatic small cell carcinoma (2011) Prostate, 71, pp. 1668-1679. , COI: 1:CAS:528:DC%2BC3MXht1Srs7jF, PID: 21432867 Teta, R., Irollo, E., Della Sala, G., Pirozzi, G., Mangoni, A., Costantino, V., Smenamides A and B, chlorinated peptide/polyketide hybrids containing a dolapyrrolidinone unit from the Caribbean sponge Smenospongia aurea. Evaluation of their role as leads in antitumor drug research (2013) Mar Drugs, 11, pp. 4451-4463. , PID: 24217287 Wang, Y., Nangia-Makker, P., Tait, L., Balan, V., Hogan, V., Pienta, K.J., Raz, A., regulation of prostate cancer progression by Galectin-3 (2009) Am J Pathol, 174, pp. 1515-1523. , COI: 1:CAS:528:DC%2BD1MXksVOku7Y%3D, PID: 19286570}, document_type={Journal Article, }, affiliation={CNR, Istituto di Biostrutture e Bioimmagini (Via Mezzocannone Site and Headquarters), 80134, Naples, Italy. giovanni.roviello@cnr.it., Institute of Pharmacy, Yerevan State University, 1 A. Manoogian Str., 0025, Yerevan, Armenia., Centro Regionale di Competenza (CRdC) Tecnologie, Via Nuova Agnano, 11, 80125, Naples, Italy., }, ibbaffiliation={1}, } @article{IBB_ID_53389, author={Roviello GN, Iannitti R, Roviello V, Palumbo R, Simonyan H, Vicidomini C}, title={Synthesis and biological evaluation of a novel Amadori compound}, date={2017 Feb}, journal={Amino Acids (ISSN: 0939-4451, 1438-2199, 1438-2199electronic)}, year={2017}, fullvolume={342}, volume={342}, pages={327--335}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85010789875&doi=10.1007%2fs00726-016-2363-4&partnerID=40&md5=e77e3220c097d086e5065e763e47bab9}, abstract={Here, we report the synthesis, purification, ESI MS and NMR characterization, as well as the SEM analysis of a fructosyl thiophenyl-substituted triazolyl-thione l-alanine (denominated Fru-l-TTA). This novel fructosyl derivative was obtained by solution synthesis using the Amadori reaction, in analogy to other natural fructosyl-amino acids, and fully characterized. In particular, we report an accurate NMR/MS/SEM characterization of Fru-l-TTA alongside some biological properties, and investigated to compare the properties of the artificial derivative of this work with the natural counterparts. In particular, Fru-l-TTA shares with natural fructosyl-amino acids the possibility to inhibit the colony formation of prostate cancer cells and additionally decreases their migration. © 2016, Springer-Verlag Wien.}, keywords={Amadori Compound, Esi Ms, Glycated Amino Acid, 3 [4 Propyl 3 (2 Thienyl) 5 Thioxo 1, 4 Triazol 1 Yl] 2 [(2, 5 Tetrahydroxytetrahydropyran 2 Yl)methylamino ]propanoic Acid, Antineoplastic Agent, Unclassified Drug, 3-(4-Propyl-3-(2-Thienyl)-5-Thioxo-1, 4-Triazol-1-Yl)-2-((2, 5-Tetrahydroxytetrahydropyran-2-Yl)methylamino)propanoic Acid, Alanine, Copper, Fructose, Amadori Rearrangement, Article, Cancer Cell, Cancer Inhibition, Cell Adhesion, Cell Migration, Chromatography, Controlled Study, Drug Mechanism, Drug Purification, Drug Structure, Drug Synthesis, Electrospray, Human, Human Cell, In Vitro Study, Mass Spectrometry, Metastasis, Nuclear Magnetic Resonance, Prostate Cancer, Scanning Electron Microscopy, Analogs And Derivatives, Cell Motion, Chemistry, Drug Effects, Drug Screening, Electrospray Mass Spectrometry, Metabolism, Nuclear Magnetic Resonance Spectroscopy, Procedures, Prostate Tumor, Tumor Cell Line, Cell Movement, Chemistry Techniques, Synthetic, Drug Screening Assays, Antitumor, Prostatic Neoplasms, Electrospray Ionization, Alanine Analogs, Derivatives Chemistry Pharmacology , Antineoplastic Agents Chemical Synthesis Chemistry Pharmacology , Cell Movement Drug Effects , Copper Metabolism , Antitumor Methods , Fructose Analogs, Male , Prostatic Neoplasms Drug Therapy, }, references={Amato, F., Tomaiuolo, R., Borbone, N., Design, synthesis and biochemical investigation, by in vitro luciferase reporter system, of peptide nucleic acids as new inhibitors of miR-509-3p involved in the regulation of cystic fibrosis disease-gene expression (2014) Med Chem Commun, 5, pp. 68-71. , COI: 1:CAS:528:DC%2BC3sXhvFGkt7f Arabzadeh, A., Beauchemin, N., Cell adhesion molecules in colon cancer metastasis (2010) Metastasis of colorectal cancer, Cancer metastasis—biology and treatment, 14, pp. 173-203 Brewer, G.J., Dick, R.D., Grover, D.K., LeClaire, V., Tseng, M., Wicha, M., Pienta, K., Merajver, S.D., Treatment of metastatic cancer with tetrathiomolybdate, an anticopper, antiangiogenic agent: phase I study (2000) Clin Cancer Res, 6, pp. 1-10. , COI: 1:CAS:528:DC%2BD3cXhtVequrs%3D, PID: 10656425 Campo, V.L., Carvalho, I., Allman, S., Davis, B.G., Field, R.A., Chemical and chemoenzymatic synthesis of glycosyl-amino acids and glycopeptides related to Trypanosoma cruzi mucins (2007) Org Biomol Chem, 5, pp. 2645-2657. , COI: 1:CAS:528:DC%2BD2sXosVShtLg%3D, PID: 18019540 Caruso, U., Panunzi, B., Roviello, G.N., Roviello, G., Tingoli, M., Tuzi, A., Synthesis, structure and reactivity of amino-benzodifurane derivatives (2009) C R Chim, 12, pp. 622-634. , COI: 1:CAS:528:DC%2BD1MXltVajsbs%3D Denoyer, D., Clatworthy, S.A., Masaldan, S., Meggyesy, P.M., Cater, M.A., Heterogeneous copper concentrations in cancerous human prostate tissues (2015) Prostate, 75, pp. 1510-1517. , COI: 1:CAS:528:DC%2BC2MXhtlelsL7M, PID: 26012532 Denoyer, D., Masaldan, S., Fontaine, S.L., Cater, M.A., Targeting copper in cancer therapy: ‘Copper That Cancer’ (2015) Metallomics, 7, pp. 1459-1476. , COI: 1:CAS:528:DC%2BC2MXhsVSnt7jF, PID: 26313539 Estendorfer, S., Ledl, F., Severin, T., Formation of an aminoreductone from glucose (1990) Angew Chem Int Ed Engl, 29, pp. 536-537 Gallas, K., Pototschnig, G., Adanitsch, F., Stütz, A.E., Wrodnigg, T.M., The Amadori rearrangement as glycoconjugation method: synthesis of non-natural C-glycosyl type glycoconjugates (2012) Beilstein J Org Chem, 8, pp. 1619-1629. , COI: 1:CAS:528:DC%2BC38XhsFSitLfK, PID: 23209494 Glinsky, G.V., Price, J.E., Glinsky, V.V., Mossine, V.V., Kiriakova, G., Metcalf, J.B., Inhibition of human breast cancer metastasis in nude mice by synthetic glycoamines (1996) Cancer Res, 56, pp. 5319-5324. , COI: 1:CAS:528:DyaK28Xntl2mtr8%3D, PID: 8968076 Gruner, S.A.W., Locardi, E., Lohof, E., Kessler, H., Carbohydrate-based mimetics in drug design: sugar amino acids and carbohydrate scaffolds (2002) Chem Rev, 102, pp. 491-514. , COI: 1:CAS:528:DC%2BD38XotVylug%3D%3D, PID: 11841252 Horikawa, H., Okada, M., Nakamura, Y., Sato, A., Iwamoto, N., Production of hydroxyl radicals and α-dicarbonyl compounds associated with amadori compound-Cu 2 complex degradation (2002) Free Radic Res, 36, pp. 1059-1065. , COI: 1:CAS:528:DC%2BD38Xos1agsLg%3D, PID: 12516876 Jemal, A., Bray, F., Center, M.M., Ferlay, J., Ward, E., Forman, D., Global cancer statistics (2011) CA Cancer J Clin, 61, pp. 69-90. , PID: 21296855 Kumar, V., Ramesh, N.G., A versatile strategy for the synthesis of N-linked glycoamino acids from glycals (2007) Org Biomol Chem, 5, pp. 3847-3858. , COI: 1:CAS:528:DC%2BD2sXhtlSmur%2FN, PID: 18004466 Kuo, H.W., Chen, S.F., Wu, C.C., Chen, D.R., Lee, J.H., Serum and tissue trace elements in patients with breast cancer in Taiwan (2002) BTER Biol Trace Elem Res, 89, pp. 1-12. , COI: 1:CAS:528:DC%2BD38XosF2lsrk%3D Kurland, N.E., Kundu, J., Pal, S., Kundu, S.C., Yadavalli, V.K., Self-assembly mechanisms of silk protein nanostructures on two-dimensional surfaces (2012) Soft Matter, 8, pp. 4952-4959. , COI: 1:CAS:528:DC%2BC38Xlt1ygt78%3D Marasco, D., Messor, L., Marzo, T., Merlino, A., Oxaliplatin vs. cisplatin: competition experiments on their binding to lysozyme (2015) Dalton Trans, 44, pp. 10392-10398. , COI: 1:CAS:528:DC%2BC2MXnsVaqtLg%3D, PID: 25974859 Mehlen, P., Puisieux, A., Metastasis: a question of life or death (2006) Nat Rev Cancer, 6, pp. 449-458. , COI: 1:CAS:528:DC%2BD28XkvVyltrY%3D, PID: 16723991 Milano, G., Musumeci, D., Gaglione, M., Messere, A., An alternative strategy to synthesize PNA and DNA magnetic conjugates forming nanoparticle assembly based on PNA/DNA duplexes (2010) Mol BioSyst, 6, pp. 553-561. , COI: 1:CAS:528:DC%2BC3cXit1Sntr8%3D, PID: 20174683 Moccia, M., Roviello, G.N., Bucci, E.M., Pedone, C., Saviano, M., Synthesis of a l-lysine-based alternate alpha, epsilon-peptide: a novel linear polycation with nucleic acids-binding ability (2010) Int J Pharm, 397, pp. 179-183. , COI: 1:CAS:528:DC%2BC3cXhtVGisbzF, PID: 20599488 Mossine, V.V., Mawhinney, T.P., Nα-(1-deoxy-d-fructos-1-yl)-l-histidine (“d-fructose-l-histidine”): a potent copper chelator from tomato powder (2007) J Agric Food Chem, 55, pp. 10373-10381. , COI: 1:CAS:528:DC%2BD2sXhtlWmu7vE, PID: 18004802 Mossine, V.V., Chopra, P., Mawhinney, T.P., Interaction of tomato lycopene and ketosamine against rat prostate tumorigenesis (2008) Cancer Res, 68, pp. 4384-4391. , COI: 1:CAS:528:DC%2BD1cXmsFKmu70%3D, PID: 18519700 Mottram, D.S., Flavor compounds formed during the Maillard reaction: thermally generated flavors (1994) Maillard, Microw Extrus Process, 543, pp. 104-126. , COI: 1:CAS:528:DyaK2cXhtVGiurY%3D Musumeci, D., Amato, J., Randazzo, A., Novellino, E., Giancola, C., Montesarchio, D., Pagano, B., G-quadruplex on oligo affinity support (G4-OAS): an easy affinity chromatography-based assay for the screening of G-quadruplex ligands (2014) Anal Chem, 86, pp. 4126-4130. , COI: 1:CAS:528:DC%2BC2cXmtVOhsLo%3D, PID: 24725064 Pan, Q., Kleer, C.G., van Golen, K.L., Irani, J., Bottema, K.M., Bias, C., De Carvalho, M., Merajver, S.D., Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and angiogenesis (2002) Cancer Res, 62, pp. 4854-4859. , COI: 1:CAS:528:DC%2BD38Xmslylur4%3D, PID: 12208730 Poletto, M., Malfatti, M.C., Dorjsuren, D., Scognamiglio, P.L., Marasco, D., Vascotto, C., Jadhav, A., Tell, G., Inhibitors of the apurinic/apyrimidinic endonuclease 1 (APE1)/nucleophosmin (NPM1) interaction that display anti-tumor properties (2016) Mol Carcinog, 55, pp. 688-704. , COI: 1:CAS:528:DC%2BC2MXmtlKjtr0%3D, PID: 25865359 Rakosi, K., Szolomajer-Csikos, O., Kalmar, L., Szurmai, Z., Kerekgyarto, J., Toth, G.K., Synthesis of N-glycopeptides applying glycoamino acid building blocks with a combined Fmoc/Boc strategy (2011) Protein Pept Lett PPL, 18, pp. 679-683. , COI: 1:CAS:528:DC%2BC3MXnvVGrurc%3D Rambaruth, N.D., Dwek, M.V., Cell surface glycan–lectin interactions in tumor metastasis (2011) Acta Histochem, 113, pp. 591-600. , COI: 1:CAS:528:DC%2BC3MXntFKmsL4%3D, PID: 21501858 Risseeuw, M.D., Overhand, M., Fleet, G.W., Simone, M.I., A compendium of sugar amino acids (SAA): scaffolds, peptide- and glyco-mimetics (2007) Tetrahedron Asymmetry, 18, pp. 2001-2010. , COI: 1:CAS:528:DC%2BD2sXhtFSiur7P Roviello, G.N., Moccia, M., Sapio, R., Valente, M., Bucci, E.M., Castiglione, M., Pedone, C., Musumeci, D., Synthesis, characterization and hybridization studies of new nucleo-γ-peptides based on diaminobutyric acid (2006) J Pept Sci, 12, pp. 829-835. , COI: 1:CAS:528:DC%2BD2sXktFar, PID: 17131297 Roviello, G.N., Musumeci, D., Pedone, C., Bucci, E.M., Synthesis, characterization and hybridization studies of an alternate nucleo-epsilon/gamma-peptide: complexes formation with natural nucleic acids (2010) Amino Acids, 38, pp. 103-111. , COI: 1:CAS:528:DC%2BC3cXhtVehtbc%3D, PID: 19067107 Roviello, G.N., Gaetano, S.D., Capasso, D., Franco, S., Crescenzo, C., Bucci, E.M., Pedone, C., RNA-binding and viral reverse transcriptase inhibitory activity of a novel cationic diamino acid-based peptide (2011) J Med Chem, 54, pp. 2095-2101. , COI: 1:CAS:528:DC%2BC3MXivFyhsrg%3D, PID: 21391685 Roviello, G.N., Ricci, A., Bucci, E.M., Pedone, C., Synthesis, biological evaluation and supramolecular assembly of novel analogues of peptidyl nucleosides (2011) Mol BioSyst, 7, pp. 1773-1778. , COI: 1:CAS:528:DC%2BC3MXksFSitLg%3D, PID: 21431179 Roviello, G.N., Vicidomini, C., Di Gaetano, S., Capasso, D., Musumeci, D., Roviello, V., Solid phase synthesis and RNA-binding activity of an arginine-containing nucleopeptide (2016) RSC Adv., 6, pp. 14140-14148. , COI: 1:CAS:528:DC%2BC28Xhtl2qt70%3D Russo, A., Aiello, C., Grieco, P., Marasco, D., Targeting “Undruggable” proteins: design of synthetic cyclopeptides (2016) CMC, 23, pp. 748-762. , COI: 1:CAS:528:DC%2BC28Xlt1KjtL0%3D Saghyan, A.S., Simonyan, H.M., Petrosyan, S.G., Geolchanyan, A.V., Roviello, G.N., Musumeci, D., Roviello, V., Thiophenyl-substituted triazolyl-thione l-alanine: asymmetric synthesis, aggregation and biological properties (2014) Amino Acids, 46, pp. 2325-2332. , COI: 1:CAS:528:DC%2BC2cXhtVaju7jI, PID: 24952728 Shevde, L.A., King, J.A., Cell adhesion molecules in breast cancer invasion and metastasis (2007) Metastasis of Breast Cancer, Cancer Metastasis—Biology and Treatment, 11, pp. 111-136 Simeone, L., Milano, D., De Napoli, L., Irace, C., Di Pascale, A., Boccalon, M., Tecilla, P., Montesarchio, D., Design, synthesis and characterisation of guanosine-based amphiphiles (2011) Chem Eur J, 17, pp. 13854-13865. , COI: 1:CAS:528:DC%2BC3MXhsVWls7%2FO, PID: 22052615 Tai, S., Sun, Y., Squires, J.M., Zhang, H., Oh, W.K., Liang, C.-Z., Huang, J., PC3 is a cell line characteristic of prostatic small cell carcinoma (2011) Prostate, 71, pp. 1668-1679. , COI: 1:CAS:528:DC%2BC3MXht1Srs7jF, PID: 21432867 Titirici, M., Antonietti, M., Baccile, N., Hydrothermal carbon from biomass: a comparison of the local structure from poly- to monosaccharides and pentoses/hexoses (2008) Green Chem., 10, pp. 1204-1212. , COI: 1:CAS:528:DC%2BD1cXht12gu7bN Wang, Y., Nangia-Makker, P., Tait, L., Balan, V., Hogan, V., Pienta, K.J., Raz, A., Regulation of prostate cancer progression by galectin-3 (2009) Am J Pathol, 174, pp. 1515-1523. , COI: 1:CAS:528:DC%2BD1MXksVOku7Y%3D, PID: 19286570}, document_type={Journal Article, }, affiliation={CNR, Istituto di Biostrutture e Bioimmagini, Via Mezzocannone site and Headquarters, Naples, 80134, Italy Centro Regionale di Competenza (CRdC) Tecnologie, Via Nuova Agnano, 11, Naples, 80125, Italy Department of Pharmacy, Yerevan State University, 1 A. Manoogian Str., Yerevan, 0025, Armenia}, ibbaffiliation={1}, } @article{IBB_ID_53385, author={Roviello GN, Vicidomini C, Costanzo V, Roviello V}, title={Nucleic acid binding and other biomedical properties of artificial oligolysines}, date={2016 Nov}, journal={International Journal Of Nanomedicine}, year={2016}, fullvolume={267}, volume={267}, pages={5897--5904}, url={}, abstract={In the present study, we report the interaction of an artificial oligolysine (referred to as AOL) realized in our laboratory with targets of biomedical importance. These included polyinosinic acid (poly rI) and its complex with polycytidylic acid (poly I:C), RNAs with well-known interferon-inducing ability, and double-stranded (ds) DNA. The ability of the peptide to bind both single-stranded poly rI and ds poly I:C RNAs emerged from our circular dichroism (CD) and ultraviolet (UV) studies. In addition, we found that AOL forms complexes with dsDNA, as shown by spectroscopic binding assays and UV thermal denaturation experiments. These findings are encouraging for the possible use of AOL in biomedicine for nucleic acid targeting and oligonucleotide condensation, with the latter being a key step preceding their clinical application. Moreover, we tested the ability of AOL to bind to proteins, using serum albumin as a model protein. We demonstrated the oligolysine–protein binding by CD experiments which suggested that AOL, positively charged under physiological conditions, binds to the protein regions rich in anionic residues. Finally, the morphology characterization of the solid oligolysine, performed by scanning electron microscopy, showed different crystal forms including cubic-shaped crystals confirming the high purity of AOL.}, keywords={, }, references={}, document_type={Journal Article, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_53109, author={Gargiulo S, Anzilotti S, Coda AR, Gramanzini M, Greco A, Panico M, Vinciguerra A, Zannetti A, Vicidomini C, Dolle F, Pignataro G, Quarantelli M, Annunziato L, Brunetti A, Salvatore M, Pappata S}, title={Imaging of brain TSPO expression in a mouse model of amyotrophic lateral sclerosis with (18)F-DPA-714 and micro-PET/CT}, date={2016 Jan 27}, journal={Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 1619-7070print)}, year={2016}, fullvolume={294}, volume={294}, pages={1348--1359}, url={https://www2.scopus.com/inward/record.uri?eid=2-s2.0-84955614300&partnerID=40&md5=2184058c348d2cba42ba2dd9fb3b1a01}, abstract={Purpose: To evaluate the feasibility and sensitivity of 18F-DPA-714 for the study of microglial activation in the brain and spinal cord of transgenic SOD1G93A mice using high-resolution PET/CT and to evaluate the Iba1 and TSPO expression with immunohistochemistry. Methods: Nine symptomatic SOD1G93A mice (aged 117 ± 12.7 days, clinical score range 1 – 4) and five WT SOD1 control mice (aged 108 ± 28.5 days) underwent 18F-DPA-714 PET/CT. SUV ratios were calculated by normalizing the cerebellar (rCRB), brainstem (rBS), motor cortex (rMCX) and cervical spinal cord (rCSC) activities to that of the frontal association cortex. Two WT SOD1 and six symptomatic SOD1G93A mice were studied by immunohistochemistry. Results: In the symptomatic SOD1G93A mice, rCRB, rBS and rCSC were increased as compared to the values in WT SOD1 mice, with a statistically significantly difference in rBS (2.340 ± 0.784 vs 1.576 ± 0.287, p = 0.014). Immunofluorescence studies showed that TSPO expression was increased in the trigeminal, facial, ambiguus and hypoglossal nuclei, as well as in the spinal cord, of symptomatic SOD1G93A mice and was colocalized with increased Iba1 staining. Conclusion: Increased 18F-DPA-714 uptake can be detected with high-resolution PET/CT in the brainstem of transgenic SOD1G93A mice, a region known to be a site of degeneration and increased microglial activation in amyotrophic lateral sclerosis, in agreement with increased TSPO expression in the brainstem nuclei shown by immunostaining. Therefore, 18F-DPA-714 PET/CT might be a suitable tool to evaluate microglial activation in the SOD1G93A mouse model. © 2016, Springer-Verlag Berlin Heidelberg.}, keywords={18f-Dpa-714, Sod1g93a, Tspo, Mice, Pet Ct, Carrier Protein, N Diethyl 2 [2 (4 (2fluoroethoxy)phenyl) 5, 7 Dimethylpyrazolo[1, 5 A]pyrimidin 3 Yl]acetamide F 18, Tracer, Translocator Protein 18, Unclassified Drug, 4 Aminobutyric Acid Receptor, Bzrp Protein, Mouse, N-Diethyl-2-(2-(4-(2-Fluoroethoxy)phenyl)-5, 7-Dimethylpyrazolo(1, 5-A)pyrimidin-3-Yl)acetamide, Pyrazole Derivative, Pyrimidine Derivative, Amyotrophic Lateral Sclerosis, Animal Care, Animal Experiment, Animal Model, Article, Association Cortex, Body Constitution, Body Weight, Brain Stem, Cervical Spinal Cord, Computer Assisted Emission Tomography, Controlled Study, Frontal Cortex, Histocompatibility Complex, Immunofluorescence, Immunohistochemistry, Motor Cortex, Neuroimaging, Nonhuman, Protein Expression, Diagnostic Imaging, Disease Model, Gene Expression Regulation, Metabolism, Positron Emission Tomography-Computed Tomography, Transport At The Cellular Level, Biological Transport, Positron Emission Tomography Computed Tomography, Gaba, Amyotrophic Lateral Sclerosis Diagnostic Imaging Metabolism , Brain Diagnostic Imaging Metabolism , Pyrazoles Metabolism , Pyrimidines Metabolism , Gaba Metabolism, }, references={Ferraiuolo, L., Kirby, J., Grierson, A.J., Sendtner, M., Shaw, P.J., Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis (2011) Nat Rev Neurol, 7, pp. 616-630. , COI: 1:CAS:528:DC%2BC3MXhsVahur3O, PID: 2205191 Cleveland, D.W., Rothstein, J.D., From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS (2001) Nat Rev Neurosci, 2, pp. 806-819. , COI: 1:CAS:528:DC%2BD38Xmt1WitLs%3D, PID: 11715057 Van Damme, P., Robberecht, W., Recent advances in motor neuron disease (2009) Curr Opin Neurol, 22, pp. 486-492. , PID: 19593125 Kiernan, M.C., Vucic, S., Cheah, B.C., Turner, M.R., Eisen, A., Hardiman, O., Amyotrophic lateral sclerosis (2011) Lancet, 377, pp. 942-955. , COI: 1:CAS:528:DC%2BC3MXjtFWgsL8%3D, PID: 21296405 McGeer, P.L., McGeer, E.G., Inflammatory processes in amyotrophic lateral sclerosis (2002) Muscle Nerve, 26, pp. 459-470. , COI: 1:CAS:528:DC%2BD38Xot1Ggs7Y%3D, PID: 12362410 Appel, S.H., Zhao, W., Beers, D.R., Henkel, J.S., The microglial–motoneuron dialogue in ALS (2011) Acta Myol, 30, pp. 4-8. , COI: 1:CAS:528:DC%2BC3MXhtFCqsLnN, PID: 21842586 Philips, T., Robberecht, W., Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease (2011) Lancet Neurol, 10, pp. 253-263. , COI: 1:CAS:528:DC%2BC3MXit1Wktr8%3D, PID: 21349440 Brettschneider, J., Toledo, J.B., Van Deerlin, V.M., Elman, L., McCluskey, L., Lee, V.M., Microglial activation correlates with disease progression and upper motor neuron clinical symptoms in amyotrophic lateral sclerosis (2012) PLoS One, 7, p. e39216. , COI: 1:CAS:528:DC%2BC38XptVOjsL0%3D, PID: 22720079 Evans, M.C., Couch, Y., Sibson, N., Turner, M.R., Inflammation and neurovascular changes in amyotrophic lateral sclerosis (2013) Mol Cell Neurosci, 53, pp. 34-41. , COI: 1:CAS:528:DC%2BC38XhslCntbfP, PID: 23110760 Kawamata, T., Akyyama, H., Yamada, T., McGeer, P.L., Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissues (1992) Am J Pathol, 140, pp. 691-707. , COI: 1:STN:280:DyaK387ovFSrsQ%3D%3D, PID: 1347673 Gurney, M.E., Pu, H., Chiu, A.Y., Dal Canto, M.C., Polchow, C.Y., Alexander, D.D., Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation (1994) Science, 264, pp. 1772-1775. , COI: 1:CAS:528:DyaK2cXksFGisbk%3D, PID: 8209258 Henkel, J.S., Engelhardt, J.I., Siklos, L., Simpson, E.P., Kim, S.H., Pan, T., Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue (2004) Ann Neurol, 55, pp. 221-235. , COI: 1:CAS:528:DC%2BD2cXhs1SgtbY%3D, PID: 14755726 Ferrucci, M., Spalloni, A., Bartalucci, A., Cantafora, E., Fulceri, F., Nutini, M., A systematic study of brainstem motor nuclei in a mouse model of ALS, the effects of lithium (2010) Neurobiol Dis, 37, pp. 370-383. , COI: 1:CAS:528:DC%2BC3cXos1Cr, PID: 19874893 Leichsenring, A., Linnartz, B., Zhu, X.R., Lubbert, H., Stichel, C.C., Ascending neuropathology in the CNS of a mutant SOD1 mouse model of amyotrophic lateral sclerosis (2006) Brain Res, 1096, pp. 180-195. , COI: 1:CAS:528:DC%2BD28Xmt1yisr8%3D, PID: 16737688 Petrik, M.S., Wilson, J.M., Grant, S.C., Blackband, S.J., Tabata, R.C., Shan, X., Magnetic resonance microscopy and immunohistochemistry of the CNS of the mutant SOD murine model of ALS reveals widespread neural deficits (2007) Neuromolecular Med, 9, pp. 216-229. , COI: 1:CAS:528:DC%2BD2sXhtV2gt7jO, PID: 17914180 Ozdinler, P.H., Benn, S., Yamamoto, T.H., Güzel, M., Brown, R.H., Jr., Macklis, J.D., Corticospinal motor neurons and related subcerebral projection neurons undergo early and specific neurodegeneration in hSOD1G93A transgenic ALS mice (2011) J Neurosci, 31, pp. 4166-4177. , COI: 1:CAS:528:DC%2BC3MXjvFWmtb4%3D, PID: 21411657 Chung, Y.H., Joo, K.M., Lee, Y.J., Shin, D.H., Cha, C.I., Reactive astrocytes express PARP in the central nervous system of SOD(G93A) transgenic mice (2004) Brain Res, 1003, pp. 199-204. , COI: 1:CAS:528:DC%2BD2cXhvFaitbg%3D, PID: 15019581 Banati, R.B., Visualising microglial activation in vivo (2002) Glia, 40, pp. 206-217. , PID: 12379908 Jacobs, A.H., Tavitian, B., Noninvasive molecular imaging of neuroinflammation (2012) J Cereb Blood Flow Metab, 32, pp. 1393-1415. , COI: 1:CAS:528:DC%2BC38XpvVSjs7Y%3D, PID: 22549622 Chen, M.K., Guilarte, T.R., Translocator protein 18 kDa (TSPO): molecular sensor of brain injury and repair (2008) Pharmacol Ther, 118, pp. 1-17. , COI: 1:CAS:528:DC%2BD1cXlvVSqsb0%3D, PID: 18374421 Scarf, A.M., Kassiou, M., The translocator protein (2011) J Nucl Med, 52, pp. 677-680. , COI: 1:CAS:528:DC%2BC3MXnsleltbw%3D, PID: 21498529 Turner, M.R., Cagnin, A., Turkheimer, F.E., Miller, C.C., Shaw, C.E., Brooks, D.J., Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study (2004) Neurobiol Dis, 15, pp. 601-609. , COI: 1:CAS:528:DC%2BD2cXivVKmsro%3D, PID: 15056468 Corcia, P., Tauber, C., Vercoullie, J., Arlicot, N., Prunier, C., Praline, J., Molecular imaging of microglial activation in amyotrophic lateral sclerosis (2012) PLoS One, 7, p. e52941. , COI: 1:CAS:528:DC%2BC3sXptVSgtg%3D%3D, PID: 23300829 Zürcher, N.R., Loggia, M.L., Lawson, R., Chonde, D.B., Izquierdo-Garcia, D., Yasek, J.E., Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28 (2015) Neuroimage Clin, 7, pp. 409-414. , PID: 25685708 Venneti, S., Wang, G., Nguyen, J., Wiley, C.A., The positron emission tomography ligand DAA1106 binds with high affinity to activated microglia in human neurological disorders (2008) J Neuropathol Exp Neurol, 67, pp. 1001-1010. , PID: 18800007 Doorduin, J., Klein, H.C., Dierckx, R.A., James, M., Kassiou, M., de Vries, E.F., [11C]-DPA-713 and [18F]-DPA-714 as new PET tracers for TSPO: a comparison with [11C]-(R)-PK11195 in a rat model of herpes encephalitis (2009) Mol Imaging Biol, 11, pp. 386-398. , PID: 19330384 Abourbeh, G., Theze, B., Maroy, R., Dubois, A., Brulon, V., Fontyn, Y., Imaging microglial/macrophage activation in spinal cords of experimental autoimmune encephalomyelitis rats by positron emission tomography using the mitochondrial 18 kDa translocator protein radioligand [18F]DPA-714 (2012) J Neurosci, 32, pp. 5728-5736. , COI: 1:CAS:528:DC%2BC38XmslOiu74%3D, PID: 22539835 Chauveau, F., Van Camp, N., Dollé, F., Kuhnast, B., Hinnen, F., Damont, A., Comparative evaluation of the translocator protein radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a rat model of acute neuroinflammation (2009) J Nucl Med, 50, pp. 468-476. , COI: 1:CAS:528:DC%2BD1MXktVyns7s%3D, PID: 19223401 Martin, A., Boisgard, R., Theze, B., Van Camp, N., Kuhnast, B., Damont, A., Evaluation of the PBR/TSPO radioligand [(18)F]DPA-714 in a rat model of focal cerebral ischemia (2010) J Cereb Blood Flow Metab, 30, pp. 230-241. , COI: 1:CAS:528:DC%2BC3cXos1Sh, PID: 19794397 Arlicot, N., Vercouillie, J., Ribeiro, M.J., Tauber, C., Venel, Y., Baulieu, J.L., Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation (2012) Nucl Med Biol, 39, pp. 570-578. , COI: 1:CAS:528:DC%2BC38XmtFahtbY%3D, PID: 22172392 Vicidomini, C., Panico, M., Greco, A., Gargiulo, S., Coda, A.R., Zannetti, A., In vivo imaging and characterization of [18F]DPA-714, a potential new TSPO ligand, in mouse brain and peripheral tissues using small-animal PET (2014) Nucl Med Biol, 42, pp. 309-316. , PID: 25537727 Achilli, F., Boyle, S., Kieran, D., Chia, R., Hafezparast, M., Martin, J.E., The SOD1 transgene in the G93A mouse model of amyotrophic lateral sclerosis lies on distal mouse chromosome 12 (2005) Amyotroph Lateral Scler Other Motor Neuron Disord, 6, pp. 111-114. , COI: 1:CAS:528:DC%2BD2MXltFymu7s%3D, PID: 16036435 Solomon, J.A., Tarnopolsky, M.A., Hamadeh, M.J., One universal common endpoint in mouse models of amyotrophic lateral sclerosis (2011) PLoS One, 6, p. e20582. , COI: 1:CAS:528:DC%2BC3MXns1yjtbk%3D, PID: 21687686 Ludolph, A.C., Bendotti, C., Blaugrund, E., Chio, A., Greensmith, L., Loeffler, J.P., Guidelines for preclinical animal research in ALS/MND: A consensus meeting (2010) Amyotroph Lateral Scler, 11, pp. 38-45. , PID: 20184514 Damont, A., Hinnen, F., Kuhnast, B., Schöllhorn-Peyronneau, M.-A., James, M., Luus, C., Radiosynthesis of [18F]DPA-714, a selective radioligand for imaging the translocator protein (18 kDa) with PET (2008) J Label Comp Radiopharm, 51, pp. 286-292. , COI: 1:CAS:528:DC%2BD1cXhtVKntL3I Paxinos, G., Franklin, K.B., (2001) The mouse brain in stereotaxic coordinates, , Elsevier Academic Press, San Diego Cantarella, G., Pignataro, G., Di Benedetto, G., Anzillotti, S., Vinciguerra, A., Cuomo, O., Ischemic tolerance modulates TRAIL expression and its receptors and generates a neuroprotected phenotype (2014) Cell Death Dis, 5, p. e1331. , COI: 1:CAS:528:DC%2BC2cXhtFCkt7bJ, PID: 25032854 Autieri, M.V., cDNA cloning of human allograft inflammatory factor-1: tissue distribution, cytokine induction, and mRNA expression in injured rat carotid arteries (1996) Biochem Biophys Res Commun, 228, pp. 29-37. , COI: 1:CAS:528:DyaK28XmvVWrtrw%3D, PID: 8912632 Ito, D., Imai, Y., Ohsawa, K., Nakajima, K., Fukuuchi, Y., Kohsaka, S., Microglia-specific localisation of a novel calcium binding protein, Iba1 (1998) Brain Res Mol Brain Res, 57, pp. 1-9. , COI: 1:CAS:528:DyaK1cXjs1alsrs%3D, PID: 9630473 Sasaki, Y., Ohsawa, K., Kanazawa, H., Kohsaka, S., Imai, Y., Iba1 is an actin-cross-linking protein in macrophages/microglia (2001) Biochem Biophys Res Commun, 286, pp. 292-297. , COI: 1:CAS:528:DC%2BD3MXlvVejtrY%3D, PID: 11500035 Siegel, S., Castellan, N.J., Jr., (2000) Nonparametric statistics for the behavioral sciences, p. 143. , McGraw Hill, Sydney Nimchinsky, E.A., Young, W.G., Yeung, G., Shah, R.A., Gordon, J.W., Bloom, F.E., Differential vulnerability of oculomotor, facial, and hypoglossal nuclei in G86R superoxide dismutase transgenic mice (2000) J Comp Neurol, 416, pp. 112-125. , COI: 1:CAS:528:DC%2BD3cXktF2j, PID: 10578106 Zang, D.W., Yang, Q., Wang, H.X., Egan, G., Lopes, E.C., Cheema, S.S., Magnetic resonance imaging reveals neuronal degeneration in the brainstem of the superoxide dismutase 1 transgenic mouse model of amyotrophic lateral sclerosis (2004) Eur J Neurosci, 20, pp. 1745-1751. , PID: 15379995 Angenstein, F., Niessen, H.G., Goldschmidt, J., Vielhaber, S., Ludolph, A.C., Scheich, H., Age-dependent changes in MRI of motor brain stem nuclei in a mouse model of ALS (2004) Neuroreport, 15, pp. 2271-2274. , PID: 15371748 Bucher, S., Braunstein, K.E., Niessen, H.G., Kaulisch, T., Neumaier, M., Boeckers, T.M., Vacuolization correlates with spin-spin relaxation time in motor brainstem nuclei and behavioural tests in the transgenic G93A-SOD1 mouse model of ALS (2007) Eur J Neurosci, 26, pp. 1895-1901. , PID: 17868365 Niessen, H.G., Angenstein, F., Sander, K., Kunz, W.S., Teuchert, M., Ludolph, A.C., In vivo quantification of spinal and bulbar motor neuron degeneration in the G93A-SOD1 transgenic mouse model of ALS by T2 relaxation time and apparent diffusion coefficient (2006) Exp Neurol, 201, pp. 293-300. , COI: 1:CAS:528:DC%2BD28XpslSmtb0%3D, PID: 16740261 Evans, M.C., Serres, S., Khrapitchev, A.A., Stolp, H.B., Anthony, D.C., Talbot, K., T2-weighted MRI detects presymptomatic pathology in the SOD1 mouse model of ALS (2014) J Cereb Blood Flow Metab, 34, pp. 785-793. , COI: 1:CAS:528:DC%2BC2cXitFalsr0%3D, PID: 24496176 An, T., Shi, P., Duan, W., Zhang, S., Yuan, P., Li, Z., Oxidative stress and autophagic alteration in brainstem of SOD1-G93A mouse model of ALS (2014) Mol Neurobiol, 49, pp. 1435-1448. , COI: 1:CAS:528:DC%2BC2cXisl2msg%3D%3D, PID: 24390572 Acquadro, E., Caron, I., Tortarolo, M., Bucci, E.M., Bendotti, C., Corpillo, D., Human SOD1-G93A specific distribution evidenced in murine brain of a transgenic model for amyotrophic lateral sclerosis by MALDI imaging mass spectrometry (2014) J Proteome Res, 13, pp. 1800-1809. , COI: 1:CAS:528:DC%2BC2cXjt1yntbY%3D, PID: 24579824 Pagani, M., Chiò, A., Valentini, M.C., Öberg, J., Nobili, F., Calvo, A., Functional pattern of brain FDG-PET in amyotrophic lateral sclerosis (2014) Neurology, 83, pp. 1067-1074. , COI: 1:CAS:528:DC%2BC2cXhsFert7fJ, PID: 25122207 Zang, D.W., Cheema, S.S., Degeneration of corticospinal and bulbospinal systems in the superoxide dismutase 1(G93A G1H) transgenic mouse model of familial amyotrophic lateral sclerosis (2002) Neurosci Lett, 332, pp. 99-102. , COI: 1:CAS:528:DC%2BD38XnvVOktLs%3D, PID: 12384220 Muellauer, J., Willimayer, R., Goertzen, A.L., Wanek, T., Langer, O., Birkfellner, W., 18F, 11C and 68Ga in small animal PET imaging. Evaluation of partial volume correction methods (2013) Nuklearmedizin, 52, pp. 250-261. , COI: 1:CAS:528:DC%2BC2cXjs1anurc%3D, PID: 24337014 Kuper, C.F., Koornstra, P.J., Hameleers, D.M., Biewenga, J., Spit, B.J., Duijvestijn, A.M., The role of nasopharyngeal lymphoid tissue (1992) Immunol Today, 13, pp. 219-224. , COI: 1:CAS:528:DyaK38Xlt12ns7o%3D, PID: 1627250 Lehnert, W., Gregoire, M.C., Reilhac, A., Meikle, S.R., Characterisation of partial volume effect and region-based correction in small animal positron emission tomography (PET) of the rat brain (2012) Neuroimage, 60, pp. 2144-2157. , PID: 22387126 Hall, E.D., Oostveen, J.A., Gurney, M.E., Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS (1998) Glia, 23, pp. 249-256. , COI: 1:STN:280:DyaK1c3psFGltA%3D%3D, PID: 9633809 Alexianu, M.E., Kozovska, M., Appel, S.H., Immune reactivity in a mouse model of familial ALS correlates with disease progression (2001) Neurology, 57, pp. 1282-1289. , COI: 1:STN:280:DC%2BD3MrksVyhug%3D%3D, PID: 11591849 Graber, D.J., Hickey, W.F., Harris, B.T., Progressive changes in microglia and macrophages in spinal cord and peripheral nerve in the transgenic rat model of amyotrophic lateral sclerosis (2010) J Neuroinflammation, 28, pp. 7-8 Papadimitriou, D., Le Verche, V., Jacquier, A., Ikiz, B., Przedborski, S., Re, D.B., Inflammation in ALS and SMA: sorting out the good from the evil (2010) Neurobiol Dis, 37, pp. 493-502. , COI: 1:CAS:528:DC%2BC3cXitV2ktb4%3D, PID: 19833209 Caron, I., Micotti, E., Paladini, A., Merlino, G., Plebani, L., Forloni, G., Comparative magnetic resonance imaging and histopathological correlates in two SOD1 transgenic mouse models of amyotrophic lateral sclerosis (2015) PLoS One, 10, p. e0132159. , PID: 26132656}, document_type={Journal Article, }, affiliation={Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy., Ceinge Biotecnologie Avanzate s. c. a r. l., Via G. Salvatore 486, 80145, Naples, Italy., IRCCS SDN, Via E. Gianturco 113, 80143, Naples, Italy., Department of Advanced Biomedical Sciences, University "Federico II", Via S. Pansini 5, 80131, Naples, Italy., Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, University "Federico II", Via S. Pansini 5, 80131, Naples, Italy., CEA, Institute for Biomedical Imaging, 4 Place du General Leclerc, 91401, Orsay, France., Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy. sabina.pappata@ibb.cnr.it., Ceinge Biotecnologie Avanzate s. c. a r. l., Via G. Salvatore 486, 80145, Naples, Italy. IRCCS SDN, Via E. Gianturco 113, 80143, Naples, Italy. Department of Advanced Biomedical Sciences, University "Federico II", Via S. Pansini 5, 80131, Naples, Italy. Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, University "Federico II", Via S. Pansini 5, 80131, Naples, Italy. CEA, Institute for Biomedical Imaging, 4 Place du Général Leclerc, 91401, Orsay, France.}, ibbaffiliation={1}, } @article{IBB_ID_53207, author={Roviello GN, Vicidomini C, Di Gaetano S, Capasso D, Musumeci D, Roviello V}, title={Solid phase synthesis and RNA-binding activity of an arginine-containing nucleopeptide}, date={2016}, journal={Rsc Adv (ISSN: 2046-2069)}, year={2016}, fullvolume={372}, volume={372}, pages={14140--14148}, url={https://www2.scopus.com/inward/record.uri?eid=2-s2.0-84957561120&partnerID=40&md5=7b0387bc81c3e72fee5ed7e6ac83d35c}, abstract={Here we report the solid phase synthesis and characterization (LC-ESIMS, CD) of a cationic nucleobase-containing α-peptide, composed of both l-arginine residues and l-lysine-based nucleoamino acids sequentially present in the structure. The binding properties of this novel basic nucleopeptide towards nucleic acids were investigated by CD spectroscopy which revealed the ability of the thymine-containing oligomer to bind both adenine-containing DNA (dA12) and RNA (poly rA) molecules inducing high conformational variations in the nucleic acid structures. Moreover, the artificial oligonucleotide inhibited the enzymatic activity of HIV reverse transcriptase, opening the door to the exploitation of novel antiviral strategies inspired to this molecular tool. © The Royal Society of Chemistry 2016.}, keywords={Amino Acids, Arginine, Binding Energy, Circular Dichroism Spectroscopy, Oligonucleotides, Synthesis (chemical), Binding Properties, Cd Spectroscopy, Enzymatic Activities, Hiv Reverse Transcriptase, Molecular Tools, Nucleic Acid Structure, Nucleobases, Solid Phase Synthesis, }, references={Zatsepin, T.S., Romanova, E.A., Stetsenko, D.A., Gait, M.J., Oretskaya, T.S., Synthesis of 2′-modified oligonucleotides containing aldehyde or ethylenediamine groups (2003) Nucleosides, Nucleotides Nucleic Acids, 22, pp. 1383-138 Bell, N.M., Micklefield, J., Chemical modification of oligonucleotides for therapeutic, bioanalytical and other applications (2009) ChemBioChem, 10, pp. 2691-2703 D'Alonzo, D., Guaragna, A., Palumbo, G., Exploring the role of chirality in nucleic acid recognition (2011) Chem. Biodiversity, 8, pp. 373-413 Roviello, G.N., Benedetti, E., Pedone, C., Bucci, E.M., Nucleobase-containing peptides: An overview of their characteristic features and applications (2010) Amino Acids, 39, pp. 45-57 Roviello, G.N., Musumeci, D., Bucci, E.M., Pedone, C., Evidences for supramolecular organization of nucleopeptides: Synthesis, spectroscopic and biological studies of a novel dithymine L-serine tetrapeptide (2011) Mol. BioSyst., 7, pp. 1073-1080 Roviello, G.N., Roviello, G., Musumeci, D., Bucci, E.M., Pedone, C., Dakin-West reaction on 1-thyminyl acetic acid for the synthesis of 1,3-bis(1-thyminyl)-2-propanone, a heteroaromatic compound with nucleopeptide-binding properties (2012) Amino Acids, 43, pp. 1615-1623 Avitabile, C., Moggio, L., Malgieri, G., Capasso, D., Di Gaetano, S., Saviano, M., Pedone, C., Romanelli, A., γ Sulphate PNA (PNA S): Highly selective DNA binding molecule showing promising antigene activity (2012) PLoS One, 7 (5), p. e35774 Avitabile, C., Cimmino, A., Romanelli, A., Oligonucleotide analogues as modulators of the expression and function of noncoding RNAs (ncRNAs): Emerging therapeutics applications (2014) J. Med. Chem., 57, pp. 10220-10240 Dragulescu-Andrasi, A., Rapireddy, S., He, B., Bhattacharya, G., Hyldig-Nielsen, J.J., Zon, G., Ly, D.H., Cell-permeable peptide nucleic acid designed to bind to the 5'-untranslated region of E-cadherin transcript induces potent and sequence-specific antisense effects (2006) J. Am. Chem. Soc., 128, pp. 16104-16112 Katritzky, A.R., Narindoshvili, T., Chiral peptide nucleic acid monomers (PNAM) with modified backbones (2008) Org. Biomol. Chem., 6, pp. 3171-3176 Calabretta, A., Tedeschi, T., Di Cola, G., Corradini, R., Sforza, S., Marchelli, R., Arginine-based PNA microarrays for APOE genotyping (2009) Mol. BioSyst., 5, pp. 1323-1330 Van Der Laan, A.C., Van Amsterdam, I., Tesser, G.I., Van Boom, J.H., Yeheskiel, E.K., Synthesis of chirally pure ornithine-based PNA analogues (1998) Nucleosides Nucleotides, 17, pp. 219-231 Wada, T., Minamimoto, N., Inaki, Y., Inoue, Y., Peptide ribonucleic acids (PRNA). 2. A novel strategy for active control of DNA recognition through borate ester formation (2000) J. Am. Chem. Soc., 122, pp. 6900-6910 Sawa, N., Wada, T., Inoue, Y., Synthesis and DNA-recognition behavior of a novel peptide ribonucleic acid with a serine backbone (oxa-PRNA) (2010) Tetrahedron, 66, pp. 344-349 Roviello, G.N., Moccia, M., Sapio, R., Valente, M., Bucci, E.M., Castiglione, M., Pedone, C., Musumeci, D., Synthesis, characterization and hybridization studies of new nucleo-gamma-peptides based on diaminobutyric acid (2006) J. Pept. Sci., 12, pp. 829-835 Scognamiglio, P.L., Di Natale, C., Leone, M., Poletto, M., Vitagliano, L., Tell, G., Marasco, D., G-quadruplex DNA recognition by nucleophosmin: New insights from protein dissection (2014) Biochim. Biophys. Acta, 1840, pp. 2050-2059 Poletto, M., Malfatti, M.C., Dorjsuren, D., Scognamiglio, P.L., Marasco, D., Vascotto, C., Jadhav, A., Tell, G., Inhibitors of the apurinic/apyrimidinic endonuclease 1 (APE1)/nucleophosmin (NPM1) interaction that display anti-tumor properties (2015) Mol. Carcinog. Topalian, S.L., Kaneko, S., Gonzales, M.I., Bond, G.L., Ward, Y., Manley, J.L., Identification and functional characterization of neo-poly(A) polymerase, an RNA processing enzyme overexpressed in human tumors (2001) Mol. Cell. Biol., 21, pp. 5614-5623 Song, G., Ren, J., Recognition and regulation of unique nucleic acid structures by small molecules (2010) Chem. Commun., 46, pp. 7283-7294 Moggio, L., Romanelli, A., Gambari, R., Bianchi, N., Borgatti, M., Fabbri, E., Mancini, I., Messere, A., Alternate PNA-DNA chimeras (PNA-DNA)(n): Synthesis, binding properties and biological activity (2007) Biopolymers, 88, pp. 815-822 Saghyan, A.S., Simonyan, H.M., Petrosyan, S.G., Geolchanyan, A.V., Roviello, G.N., Musumeci, D., Roviello, V., Thiophenyl-substituted triazolyl-thione L-alanine: Asymmetric synthesis, aggregation and biological properties (2014) Amino Acids, 46, pp. 2325-2332 Roviello, G.N., Di Gaetano, S., Capasso, D., Franco, S., Crescenzo, C., Bucci, E.M., Pedone, C., RNA-binding and viral reverse transcriptase inhibitory activity of a novel cationic diamino acid-based peptide (2011) J. Med. Chem., 54, pp. 2095-2101 Guaragna, A., Roviello, G.N., D'Errico, S., Paolella, C., Palumbo, G., D'Alonzo, D., Solid phase synthesis of a novel folate-conjugated 5-aminolevulinic acid methyl ester based photosensitizer for selective photodynamic therapy (2015) Tetrahedron Lett., 56, pp. 775-778 Nguyen, L.T., Chau, J.K., Perry, N.A., De Boer, L., Zaat, S.A., Vogel, H.J., Serum stabilities of short tryptophan- and arginine-rich antimicrobial peptide analogs (2010) PLoS One, 5, p. e12684 Nielsen, P.E., Egholm, M., Berg, R.H., Buchardt, O., Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide (1991) Science, 254, pp. 1497-1500 Vicidomini, C., Panico, M.R., Greco, A., Gargiulo, S., Coda, A.R., Zannetti, A., Gramanzini, M., Pappatà, S., In vivo imaging and characterization of [(18)F]DPA-714, a potential new TSPO ligand, in mouse brain and peripheral tissues using small-animal PET (2015) Nucl. Med. Biol., 42, pp. 309-316 Musumeci, D., Riccardi, C., Montesarchio, D., G-Quadruplex Forming Oligonucleotides as Anti-HIV Agents (2015) Molecules, 20, pp. 17511-322015 Simeone, L., Milano, D., De Napoli, L., Irace, C., Di Pascale, A., Boccalon, M., Tecilla, P., Montesarchio, D., Design, Synthesis and Characterisation of Guanosine-Based Amphiphiles (2011) Chem.-Eur. J., 17, pp. 13854-13865}, document_type={Journal Article, }, affiliation={CNR, Istituto di Biostrutture e Bioimmagini-(Mezzacannone Site and Headquarters), Napoli, Italy Università di Napoli Federico II, Dipartimento di Farmacia, Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_52749, author={Santangelo G, Vitale C, Picillo M, Cuoco S, Moccia M, Pezzella D, Erro R, Longo K, Vicidomini C, Pellecchia MT, Amboni M, Brunetti A, Salvatore M, Barone P, Pappata S}, title={Apathy and striatal dopamine transporter levels in de-novo, untreated Parkinson's disease patients}, date={2015 May}, journal={Parkinsonism Relat D (ISSN: 1353-8020, 1873-5126, 1353-8020print)}, year={2015}, fullvolume={331}, volume={331}, pages={489--493}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84928587429&partnerID=40&md5=c570b0e07294ba61a94ee19c704d23f2}, abstract={Introduction: Apathy is a neuropsychiatric symptom in Parkinson's Disease (PD) which has a negative impact on quality of life and might be related in part to damage of presynaptic dopaminergic system. Little is known about relationship between striatal dopamine levels and apathy in PD patients without dementia and/or depression. The aim of the present study was to investigate the relationship between "pure apathy" and striatal dopamine uptake in untreated, drug-naïve PD patients without clinically significant dementia and/or depression. Methods: Fourteen PD patients with pure apathy and 14 PD patients without apathy, matched for age, side of motor symptoms at onset, motor disability and disease duration, underwent both neuropsychological and behavioral examination including self-rated version of the Apathy Evaluation Scale (AES-S). All patients underwent 123 I-FP-CIT (DaT-SCAN) SPECT to assess dopamine transporter (DAT) striatal uptake. Results: PD patients with apathy showed lower DAT levels in the striatum than non-apathetic patients. After Bonferroni correction the difference between groups was significant in the right caudate. Conclusions: Apathy is associated with reduced striatal dopamine transporter levels, independent of motor disability and depression in non-demented PD patients. These findings suggest that dysfunction of dopaminergic innervation in the striatum and particularly in the right caudate may contribute to development of apathy in early PD. © 2015 Elsevier Ltd.}, keywords={Apathy, Behavioral Disorders, Dopamine, Non-Motor Symptoms, Parkinson, S Disease, [123] Fp-Cit Spect, Dopamine Transporter, Ioflupane I 123, Adult, Article, Caudate Nucleus, Clinical Article, Corpus Striatum, Depression, Dopamine Brain Level, Dopamine Uptake, Female, Human, Motor Dysfunction, Parkinson Disease, Priority Journal, Single Photon Emission Computer Tomography, Aged, Cohort Analysis, Metabolism, Middle Aged, Physiology, Procedures, Retrospective Study, Scintiscanning, Cohort Studies, Dopamine Plasma Membrane Transport Proteins, Retrospective Studies, Emission-Computed, Single-Photon, Apathy Physiology , Corpus Striatum Diagnostic Imaging Metabolism , Dopamine Plasma Membrane Transport Proteins Metabolism , Parkinson Disease Diagnostic Imaging Metabolism , Single-Photon Methods, }, references={Marin, R.S., Apathy: a neuropsychiatric syndrome (1991) JNeuropsychiatr Clin Neurosci, 3, pp. 243-25 Levy, R., Dubois, B., Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits (2006) Cereb Cortex, 16, pp. 916-928 Santangelo, G., Trojano, L., Barone, P., Errico, D., Grossi, D., Vitale, C., Apathy in Parkinson's disease: diagnosis, neuropsychological correlates, pathophysiology and treatment (2013) Behav Neurol, 27, pp. 501-513 Santangelo, G., Vitale, C., Trojano, L., Errico, D., Amboni, M., Barbarulo, A.M., Neuropsychological correlates of theory of mind in patients with early Parkinson's disease (2012) Mov Disord, 27, pp. 98-105 Benito-León, J., Cubo, E., Coronell, C., Impact of apathy on health-related quality of life in recently diagnosed Parkinson's disease: the ANIMO study (2012) Mov Disord, 27, pp. 211-218. , ANIMO Study Group Benoit, M., Robert, P.H., Imaging correlates of apathy and depression in Parkinson's disease (2011) JNeurol Sci, 310, pp. 58-60 Poletti, M., Bonuccelli, U., Acute and chronic cognitive effects of levodopa and dopamine agonists on patients with Parkinson's disease: a review (2013) Ther Adv Psychopharmacol, 3, pp. 101-113 Robert, P., Onyike, C.U., Leentjens, A.F., Dujardin, K., Aalten, P., Starkstein, S., Proposed diagnostic criteria for apathy in Alzheimer's disease and other neuropsychiatric disorders (2009) Eur Psychiatry, 24, pp. 98-104 Santangelo, G., Barone, P., Cuoco, S., Raimo, S., Pezzella, D., Picillo, M., Apathy in untreated, de novo patients with Parkinson's disease: validation study of apathy evaluation scale (2014) JNeurol, 261, pp. 2319-2328 Booij, J., Hemelaar, T.G., Speelman, J.D., de Bruin, K., Janssen, A.G., van Royen, E.A., One-day protocol for imaging of the nigrostriatal dopaminergic pathway in Parkinson's disease by [123]FPCIT SPECT (1999) JNucl Med, 40, pp. 753-761 Booij, J., Speelman, J.D., Horstink, M.W., Wolters, E.C., The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism (2001) Eur J Nucl Med, 28, pp. 266-272 Laruelle, M.1., Wallace, E., Seibyl, J.P., Baldwin, R.M., Zea-Ponce, Y., Zoghbi, S.S., Graphical, kinetic, and equilibrium analyses of invivo [123I] beta-CIT binding to dopamine transporters in healthy human subjects (1994) JCereb Blood Flow, 14, pp. 982-994 Antonelli, F., Strafella, A.P., Behavioral disorders in Parkinson's disease: the role of dopamine (2014) Park Relat Disord, 20, pp. S10-S12 Roselli, F., Pisciotta, N.M., Perneczky, R., Pennelli, M., Aniello, M.S., De Caro, M.F., Severity of neuropsychiatric symptoms and dopamine transporter levels in dementia with lewy bodies: a 123I-FP-CIT SPECT study (2009) Mov Disord, 24, pp. 2097-2103 David, R., Koulibaly, M., Benoit, M., Garcia, R., Caci, H., Darcourt, J., Striatal dopamine transporter levels correlate with apathy in neurodegenerative diseases A SPECT study with partial volume effect correction (2008) Clin Neurol Neurosurg, 110, pp. 19-24 Eslinger, P.J., Moore, P., Antani, S., Anderson, C., Grossman, M., Apathy in frontotemporal dementia: behavioral and neuroimaging correlates (2012) Behav Neurol, 25, pp. 127-136 Benoit, M., Clairet, S., Koulibaly, P.M., Darcourt, J., Robert, P.H., Brain perfusion correlates of the apathy inventory dimensions of Alzheimer's disease (2004) Int J Geriatr Psychiatry, 19, pp. 864-869 Robert, G., Le Jeune, F., Lozachmeur, C., Drapier, S., Dondaine, T., Péron, J., Apathy in patients with Parkinson disease without dementia or depression: a PET study (2012) Neurology, 79, pp. 1155-1160 Reijnders, J.S., Scholtissen, B., Weber, W.E., Aalten, P., Verhey, F.R., Leentjens, A.F., Neuroanatomical correlates of apathy in Parkinson's disease: a magnetic resonance imaging study using voxel-based morphometry (2010) Mov Disord, 25, pp. 2318-2325 Botvinick, M.M., Cohen, J.D., Carter, C.S., Conflict monitoring and anterior cingulate cortex: an update (2004) Trends Cogn Sci, 8, pp. 539-546 Remy, P., Doder, M., Lees, A., Turjanski, N., Brooks, D., Depression in Parkinson's disease: loss of dopamine and noradrenaline innervation in the limbic system (2005) Brain, 128, pp. 1314-1322 Grahn, J.A., Parkinson, J.A., Owen, A.M., The role of the basal ganglia in learning and memory: neuropsychological studies (2009) Behav Brain Res, 199, pp. 53-60 Djaldetti, R., Ziv, I., Melamed, E., The mystery of motor asymmetry in Parkinson's disease (2006) Lancet Neurol, 5, pp. 796-802 Cronin-Golomb, A., Parkinson's disease as a disconnection syndrome (2010) Neuropsychol Rev, 20, pp. 191-208 Harris, E., McNamara, P., Durso, R., Apathy in patients with Parkinson disease as a function of side of onset (2013) JGeriatr Psychiatry Neurol, 26, pp. 95-104 Cubo, E., Benito-Leon, J., Coronell, C., Armesto, D., Clinical correlates of apathy in patients recently diagnosed with Parkinson's disease: the ANIMO study (2012) Neuroepidemiology, 38, pp. 48-55 Aarsland, D., Larsen, J.P., Lim, N.G., Janvin, C., Karlsen, K., Tandberg, E., Range of neuropsychiatric disturbances in patients with Parkinson's disease (1999) JNeurol Neurosurg Psychiatry, 67, pp. 492-496 Robert, G.H., Le Jeune, F., Lozachmeur, C., Drapier, S., Dondaine, T., Péron, J., Preoperative factors of apathy in subthalamic stimulated Parkinson disease: a PET study (2014) Neurology, 83, pp. 1620-1626 Dujardin, K., Sockeel, P., Delliaux, M., Destée, A., Defebvre, L., Apathy may herald cognitive decline and dementia in Parkinson's disease (2009) Mov Disord, 24, pp. 2391-2397}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Department of Psychology, Second University of Naples, Caserta, Italy IDC-Hermitage-Capodimonte, Naples, Italy University Parthenope, Naples, Italy Neurodegenerative Diseases Center, Department of Medicine and Surgery, University of Salerno, Salerno, Italy Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Naples, Italy Sobell Department of Motor Neuroscience and Movement Disorders, University College London (UCL) Institute of Neurology, London, United Kingdom Institute of Biostructure and Bioimaging, CNR, Naples, Italy Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_51992, author={Vicidomini C, Panico M, Greco A, Gargiulo S, Coda ARD, Zannetti A, Gramanzini M, Roviello GN, Quarantelli M, Alfano B, Tavitian B, Dolle F, Salvatore M, Brunetti A, Pappata S}, title={In vivo imaging and characterization of [(18)F]DPA-714, a potential new TSPO ligand, in mouse brain and peripheral tissues using small-animal PET}, date={2015 Mar}, journal={Nucl Med Biol (ISSN: 0969-8051, 0883-2897)}, year={2015}, fullvolume={253}, volume={253}, pages={309--316}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84922883622&partnerID=40&md5=11ee166d047d6864c454e3bd3601bcfd}, abstract={Introduction: The translocator protein 18kDa (TSPO), a biochemical marker of neuroinflammation, is highly expressed in the brain activated microglia and it is also expressed by peripheral inflammatory cells and normal peripheral tissues. Thus, development of radioligands for the TSPO may contribute to further understanding the in vivo TSPO function in central and peripheral inflammatory processes and other pathologies. Here, we report the biodistribution, the specific binding and the radiometabolites of [18F]DPA-714, a promising fluorinated PET radiotracer, in normal mice using a microPET/CT scanner. Methods: The in vivo biodistribution and kinetics of [18F]DPA-714 were measured in mice brain and peripheral tissues. Specific binding to TSPO sites was assessed using pharmacological competitive studies by means of saturation experiments performed by i.v. injection of 1mg/kg of unlabeled DPA-714 or 3mg/kg of unlabeled PK11195. A region of interest analysis was performed to generate time-activity curves in the brain, heart, lung, kidney, spleen and liver. Metabolites assay was performed in the plasma and peripheral organs by radio-HPLC. Results: [18F]DPA-714 reached high concentration in lung, heart, kidney and spleen, tissues well known to be rich in TSPO sites. [18F]DPA-714 kinetics were faster in the lung and slower in the kidney. Pre-injection of unlabeled DPA-714 or PK11195 inhibited about 80% of [18F]DPA-714 uptake in the lung and heart (p<0.0005). The percentage of inhibition in the kidney was lower and achieved at later times only with DPA-714 (p<0.05) but not with PK11195. Sixty minutes after radiotracer injection only unmetabolized radioligand was found in the brain, lung, heart and spleen. Conclusion: These results suggest that [18F]DPA-714 is a suitable PET ligand for imaging in mice brain and peripheral tissues since it binds with high specificity TSPO binding sites and it is almost unchanged at 60minutes after radiotracer injection in the brain and TSPO-rich regions. © 2014 Elsevier Inc.}, keywords={Biodistribution, Microglia, Neuroinflammation, Pet, Tspo, [18f]dpa-714, Benzodiazepine Receptor, N Diethyl 2 [2 [4 (2 Fluoroethoxy)phenyl] 5, 7 Dimethylpyrazolo[1, 5 A]pyrimidin 3 Yl]acetamide F 18, Radiopharmaceutical Agent, Translocator Protein 18, Unclassified Drug, Animal Experiment, Article, Brain, Competitive Inhibition, Controlled Study, Heart, High Performance Liquid Chromatography, In Vivo Study, Mouse, Nonhuman, Pet-Ct Scanner, Positron Emission Tomography, Radioactivity, Spleen, Tissue Distribution, [(18)f]dpa-714, 4 Aminobutyric Acid Receptor, Bzrp Protein, Fluorine, Isoquinoline Derivative, Ligand, N Sec Butyl 1 (2 Chlorophenyl) N Methyl 3 Isoquinolinecarboxamide, N-Diethyl-2-(2-(4-(2-Fluoroethoxy)phenyl)-5, 7-Dimethylpyrazolo(1, 5-A)pyrimidin-3-Yl)acetamide, Pyrazole Derivative, Pyrimidine Derivative, Binding Competition, Computer Assisted Tomography, Diagnostic Use, Drug Effects, Metabolism, Radiography, Scintiscanning, Fluorine Radioisotopes, Positron-Emission Tomography, X-Ray Computed, }, references={Papadopoulos, V., Baraldi, M., Guilarte, T.R., Knudsen, T.B., Lacapere, J.J., Lindemann, P., Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function (2006) Trends Pharmacol Sci, 27, pp. 402-40 Venneti, S., Lopresti, B.J., Wiley, C.A., Molecular imaging of microglia/macrophages in the brain (2013) Glia, 61, pp. 10-23 Jacobs, A.H., Tavitian, B., Noninvasive molecular imaging of neuroinflammation (2012) J Cereb Blood Flow Metab, 32, pp. 1393-1415 Chen, M.K., Guilarte, T.R., Translocator protein 18kDa (TSPO): molecular sensor of brain injury and repair (2008) Pharmacol Ther, 118, pp. 1-17 Yasuno, F., Kosaka, J., Ota, M., Higuchi, M., Ito, H., Fujimura, Y., Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with [(1)(1)C]DAA1106 (2012) Psychiatry Res, 203, pp. 67-74 Politis, M., Su, P., Piccini, P., Imaging of microglia in patients with neurodegenerative disorders (2012) Front Pharmacol, 3, p. 96 Papadopoulos, V., Lecanu, L., Translocator protein (18kDa) TSPO: an emerging therapeutic target in neurotrauma (2009) Exp Neurol, 219, pp. 53-57 Harberts, E., Datta, D., Chen, S., Wohler, J.E., Oh, U., Jacobson, S., Translocator protein 18kDa (TSPO) expression in multiple sclerosis patients (2013) J Neuroimmune Pharmacol, 8, pp. 51-57 Gavish, M., Bachman, I., Shoukrun, R., Katz, Y., Veenman, L., Weisinger, G., Enigma of the peripheral benzodiazepine receptor (1999) Pharmacol Rev, 51, pp. 629-650 Camsonne, R., Crouzel, C., Comar, D., Mazière, M., Prenant, C., Sastre, J., Synthesis of N-(11C) methyl, N-(methyl-1 propyl), (chloro-2 phenyl)-1 isoquinoleine carboxamide-3 (PK 11195): A new ligand for peripheral benzodiazepine receptors (1984) J Label Compd Radiopharm, 21, pp. 985-991 Dolle, F., Luus, C., Reynolds, A., Kassiou, M., Radiolabelled molecules for imaging the translocator protein (18kDa) using positron emission tomography (2009) Curr Med Chem, 16, pp. 2899-2923 Chauveau, F., Boutin, H., Van Camp, N., Dolle, F., Tavitian, B., Nuclear imaging of neuroinflammation: a comprehensive review of [11C]PK11195 challengers (2008) Eur J Nucl Med Mol Imaging, 35, pp. 2304-2319 Brown, A.K., Fujita, M., Fujimura, Y., Liow, J.S., Stabin, M., Ryu, Y.H., Radiation dosimetry and biodistribution in monkey and man of 11C-PBR28: a PET radioligand to image inflammation (2007) J Nucl Med, 48, pp. 2072-2079 Trapani, A., Palazzo, C., de Candia, M., Lasorsa, F.M., Trapani, G., Targeting of the translocator protein 18kDa (TSPO): a valuable approach for nuclear and optical imaging of activated microglia (2013) Bioconjug Chem, 24, pp. 1415-1428 Scarf, A.M., Kassiou, M., The translocator protein (2011) J Nucl Med, 52, pp. 677-680 Owen, D.R., Matthews, P.M., Imaging brain microglial activation using positron emission tomography and translocator protein-specific radioligands (2011) Int Rev Neurobiol, 101, pp. 19-39 Doorduin, J., de Vries, E.F., Dierckx, R.A., Klein, H.C., PET imaging of the peripheral benzodiazepine receptor: monitoring disease progression and therapy response in neurodegenerative disorders (2008) Curr Pharm Des, 14, pp. 3297-3315 Cagnin, A., Kassiou, M., Meikle, S.R., Banati, R.B., Positron emission tomography imaging of neuroinflammation (2007) Neurotherapeutics, 4, pp. 443-452 James, M.L., Fulton, R.R., Vercoullie, J., Henderson, D.J., Garreau, L., Chalon, S., DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization (2008) J Nucl Med, 49, pp. 814-822 Damont, A., Hinnen, F., Kuhnast, B., Schöllhorn-Peyronneau, M.A., James, M., Luus, C., Radiosynthesis of [18F]DPA-714, a selective radioligand for imaging the translocator protein (18kDa) with PET (2008) J Label Compd Radiopharm, 51, pp. 286-292 Arlicot, N., Vercouillie, J., Ribeiro, M.J., Tauber, C., Venel, Y., Baulieu, J.L., Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation (2012) Nucl Med Biol, 39, pp. 570-578 Martin, A., Boisgard, R., Theze, B., Van Camp, N., Kuhnast, B., Damont, A., Evaluation of the PBR/TSPO radioligand [(18)F]DPA-714 in a rat model of focal cerebral ischemia (2010) J Cereb Blood Flow Metab, 30, pp. 230-241 Doorduin, J., Klein, H.C., Dierckx, R.A., James, M., Kassiou, M., de Vries, E.F., [11C]-DPA-713 and [18F]-DPA-714 as new PET tracers for TSPO: a comparison with [11C]-(R)-PK11195 in a rat model of herpes encephalitis (2009) Mol Imaging Biol, 11, pp. 386-398 Chauveau, F., Van Camp, N., Dolle, F., Kuhnast, B., Hinnen, F., Damont, A., Comparative evaluation of the translocator protein radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a rat model of acute neuroinflammation (2009) J Nucl Med, 50, pp. 468-476 Boutin, H., Prenant, C., Maroy, R., Galea, J., Greenhalgh, A.D., Smigova, A., [18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats (2013) PLoS One, 8, p. e56441 Peyronneau, M.A., Saba, W., Goutal, S., Damont, A., Dolle, F., Kassiou, M., Metabolism and quantification of [(18)F]DPA-714, a new TSPO positron emission tomography radioligand (2013) Drug Metab Dispos, 41, pp. 122-131 Harhausen, D., Sudmann, V., Khojasteh, U., Muller, J., Zille, M., Graham, K., Specific imaging of inflammation with the 18kDa translocator protein ligand DPA-714 in animal models of epilepsy and stroke (2013) PLoS One, 8, p. e69529 Gent, Y.Y., Weijers, K., Molthoff, C.F., Windhorst, A.D., Huisman, M.C., Kassiou, M., Promising potential of new generation translocator protein tracers providing enhanced contrast of arthritis imaging by positron emission tomography in a rat model of arthritis (2014) Arthritis Res Ther, 16, p. R70 Yanamoto, K., Kumata, K., Fujinaga, M., Nengaki, N., Takei, M., Wakizaka, H., In vivo imaging and quantitative analysis of TSPO in rat peripheral tissues using small-animal PET with [18F]FEDAC (2010) Nucl Med Biol, 37, pp. 853-860 Hashimoto, K., Inoue, O., Suzuki, K., Yamasaki, T., Kojima, M., Synthesis and evaluation of 11C-PK 11195 for in vivo study of peripheral-type benzodiazepine receptors using positron emission tomography (1989) Ann Nucl Med, 3, pp. 63-71 Fookes, C.J., Pham, T.Q., Mattner, F., Greguric, I., Loc'h, C., Liu, X., Synthesis and biological evaluation of substituted [18F]imidazo[1,2-a]pyridines and [18F]pyrazolo[1,5-a]pyrimidines for the study of the peripheral benzodiazepine receptor using positron emission tomography (2008) J Med Chem, 51, pp. 3700-3712 Mattner, F., Mardon, K., Katsifis, A., Pharmacological evaluation of [123I]-CLINDE: a radioiodinated imidazopyridine-3-acetamide for the study of peripheral benzodiazepine binding sites (PBBS) (2008) Eur J Nucl Med Mol Imaging, 35, pp. 779-789 Boutin, H., Chauveau, F., Thominiaux, C., Gregoire, M.C., James, M.L., Trebossen, R., 11C-DPA-713: a novel peripheral benzodiazepine receptor PET ligand for in vivo imaging of neuroinflammation (2007) J Nucl Med, 48, pp. 573-581 Bribes, E., Carriere, D., Goubet, C., Galiegue, S., Casellas, P., Simony-Lafontaine, J., Immunohistochemical assessment of the peripheral benzodiazepine receptor in human tissues (2004) J Histochem Cytochem, 52, pp. 19-28 Papadopoulos, V., Peripheral-type benzodiazepine/diazepam binding inhibitor receptor: biological role in steroidogenic cell function (1993) Endocr Rev, 14, pp. 222-240 Maeda, J., Suhara, T., Zhang, M.R., Okauchi, T., Yasuno, F., Ikoma, Y., Novel peripheral benzodiazepine receptor ligand [11C]DAA1106 for PET: an imaging tool for glial cells in the brain (2004) Synapse, 52, pp. 283-291 Zhang, M.R., Kumata, K., Maeda, J., Yanamoto, K., Hatori, A., Okada, M., 11C-AC-5216: a novel PET ligand for peripheral benzodiazepine receptors in the primate brain (2007) J Nucl Med, 48, pp. 1853-1861 Edison, P., Archer, H.A., Gerhard, A., Hinz, R., Pavese, N., Turkheimer, F.E., Microglia, amyloid, and cognition in Alzheimer's disease: An [11C](R)PK11195-PET and [11C]PIB-PET study (2008) Neurobiol Dis, 32, pp. 412-419 Pavese, N., Gerhard, A., Tai, Y.F., Ho, A.K., Turkheimer, F., Barker, R.A., Microglial activation correlates with severity in Huntington disease: a clinical and PET study (2006) Neurology, 66, pp. 1638-1643 Messmer, K., Reynolds, G.P., Increased peripheral benzodiazepine binding sites in the brain of patients with Huntington's disease (1998) Neurosci Lett, 241, pp. 53-56 Ouchi, Y., Yoshikawa, E., Sekine, Y., Futatsubashi, M., Kanno, T., Ogusu, T., Microglial activation and dopamine terminal loss in early Parkinson's disease (2005) Ann Neurol, 57, pp. 168-175 Turner, M.R., Cagnin, A., Turkheimer, F.E., Miller, C.C., Shaw, C.E., Brooks, D.J., Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study (2004) Neurobiol Dis, 15, pp. 601-609 Cagnin, A., Rossor, M., Sampson, E.L., Mackinnon, T., Banati, R.B., In vivo detection of microglial activation in frontotemporal dementia (2004) Ann Neurol, 56, pp. 894-897 Versijpt, J., Debruyne, J.C., Van Laere, K.J., De Vos, F., Keppens, J., Strijckmans, K., Microglial imaging with positron emission tomography and atrophy measurements with magnetic resonance imaging in multiple sclerosis: a correlative study (2005) Mult Scler, 11, pp. 127-134 Vowinckel, E., Reutens, D., Becher, B., Verge, G., Evans, A., Owens, T., PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis (1997) J Neurosci Res, 50, pp. 345-353 Gerhard, A., Schwarz, J., Myers, R., Wise, R., Banati, R.B., Evolution of microglial activation in patients after ischemic stroke: a [11C](R)-PK11195 PET study (2005) Neuroimage, 24, pp. 591-595 Cosenza-Nashat, M., Zhao, M.L., Suh, H.S., Morgan, J., Natividad, R., Morgello, S., Expression of the translocator protein of 18kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain (2009) Neuropathol Appl Neurobiol, 35, pp. 306-328 Han, Z., Slack, R.S., Li, W., Papadopoulos, V., Expression of peripheral benzodiazepine receptor (PBR) in human tumors: relationship to breast, colorectal, and prostate tumor progression (2003) J Recept Signal Transduct Res, 23, pp. 225-238 Vlodavsky, E., Soustiel, J.F., Immunohistochemical expression of peripheral benzodiazepine receptors in human astrocytomas and its correlation with grade of malignancy, proliferation, apoptosis and survival (2007) J Neurooncol, 81, pp. 1-7 Gaemperli, O., Shalhoub, J., Owen, D.R., Lamare, F., Johansson, S., Fouladi, N., Imaging intraplaque inflammation in carotid atherosclerosis with 11C-PK11195 positron emission tomography/computed tomography (2012) Eur Heart J, 33, pp. 1902-1910 Varrone, A., Mattsson, P., Forsberg, A., Takano, A., Nag, S., Gulyas, B., In vivo imaging of the 18-kDa translocator protein (TSPO) with [18F]FEDAA1106 and PET does not show increased binding in Alzheimer's disease patients (2013) Eur J Nucl Med Mol Imaging, 40, pp. 921-931 Takano, A., Piehl, F., Hillert, J., Varrone, A., Nag, S., Gulyas, B., In vivo TSPO imaging in patients with multiple sclerosis: a brain PET study with [18F]FEDAA1106 (2013) EJNMMI Res, 3, p. 30 Rupprecht, R., Papadopoulos, V., Rammes, G., Baghai, T.C., Fan, J., Akula, N., Translocator protein (18kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders (2010) Nat Rev Drug Discov, 9, pp. 971-988 Daugherty, D.J., Selvaraj, V., Chechneva, O.V., Liu, X.B., Pleasure, D.E., Deng, W., A TSPO ligand is protective in a mouse model of multiple sclerosis (2013) EMBO Mol Med, 5, pp. 891-903 Fafalios, A., Akhavan, A., Parwani, A.V., Bies, R.R., McHugh, K.J., Pflug, B.R., Translocator protein blockade reduces prostate tumor growth (2009) Clin Cancer Res, 15, pp. 6177-6184 Austin, C.J., Kahlert, J., Kassiou, M., Rendina, L.M., The translocator protein (TSPO): a novel target for cancer chemotherapy (2013) Int J Biochem Cell Biol, 45, pp. 1212-1216 Guo, Q., Owen, D.R., Rabiner, E.A., Turkheimer, F.E., Gunn, R.N., Identifying improved TSPO PET imaging probes through biomathematics: the impact of multiple TSPO binding sites in vivo (2012) Neuroimage, 60, pp. 902-910}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Institute of Biostructure and Bioimaging, CNRNaples, Italy Department of Advanced Biomedical Sciences, Federico II UniversityNaples, Italy CEINGE, Biotecnologie Avanzate, s.c.a.r.l.Naples, Italy Inserm U970, PARCC, Université Paris Descartes, Hôpital Européen Georges PompidouParis, France CEA, I2BM, Service Hospitalier Frédéric JoliotOrsay, France}, ibbaffiliation={1}, } @article{IBB_ID_52298, author={Pellecchia MT, Picillo M, Santangelo G, Longo K, Moccia M, Erro R, Amboni M, Vitale C, Vicidomini C, Salvatore M, Barone P, Pappata S}, title={Cognitive performances and DAT imaging in early Parkinson's disease with mild cognitive impairment: a preliminary study}, date={2015 Feb 3}, journal={Acta Neurol Scand (ISSN: 0001-6314, 1600-0404)}, year={2015}, fullvolume={433}, volume={433}, pages={275--281}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84926355335&partnerID=40&md5=826cdc474daedbf69dcc966506f07bc6}, abstract={Objectives: Mild cognitive impairment (MCI) is a common feature in Parkinson's disease (PD). We performed an exploratory study to investigate dopaminergic nigrostriatal innervation and its cognitive correlates in early untreated PD patients with MCI as compared to cognitively intact patients. Patients and methods: A consecutive series of 34-de-novo, drug-naïve patients with PD were enrolled. They underwent [123-I] FP-CIT SPECT and comprehensive neuropsychological battery. MCI was identified in 15 of 34 patients with PD. Results: The two groups did not show any statistically significant difference in age, sex, disease duration, education, lateralization, and H&Y and Hospital Anxiety and Depression Scale scores. Logistic regression analysis showed that UPDRS-III was weakly associated with MCI (P = 0.034). Partial correlation analysis controlling for UPDRS-III and age suggested that in PD patients with MCI reduced V3″ values in the more affected caudate were correlated with reduced performances in frontal assessment battery, Trail Making Test: part B minus Part A and copy task of the Rey-Osterrieth complex figure test. Reduced V3″ values in the more and less affected putamen were significantly related with reduced performance in frontal assessment battery and in copy task of Rey-Osterrieth complex figure test, respectively. No correlation was found between neuropsychological scores and DAT availability in PD patients without MCI. Conclusions: Although preliminary, our results suggest that striatal dopamine depletion may contribute to some cognitive deficit in early never treated PD patients with MCI. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.}, keywords={Spect, Cognition, Dopamine Transporter, Early Parkinson, S Disease, Mild Cognitive Impairment, Ioflupane I 123, Adult, Article, Attention, Clinical Article, Controlled Study, Disease Duration, Disease Severity, Dsm-Iv, Executive Function, Female, Hospital Anxiety And Depression Scale, Human, Learning, Memory, Parkinson Disease, Psychologic Test, Single Photon Emission Computer Tomography, Spect Scanner, Stroop Test, Unified Parkinson Disease Rating Scale, Working Memory, 2-Carbomethoxy-8-(3-Fluoropropyl)-3-(4-Iodophenyl)tropane, Tropane Derivative, Aged, Complication, Corpus Striatum, Diagnostic Use, Metabolism, Middle Aged, Procedures, Psychological Rating Scale, Scintiscanning, Dopamine Plasma Membrane Transport Proteins, Psychiatric Status Rating Scales, Emission-Computed, Single-Photon, }, references={Williams-Gray, C.H., Foltynie, T., Brayne, C.E.G., Evolution of cognitive dysfunction in an incident Parkinson's disease cohort (2007) Brain, 130, pp. 1787-179 Elgh, E., Domellof, M., Linder, J., Cognitive function in early Parkinson's disease: a population-based study (2009) Eur J Neurol, 16, pp. 1278-1284 Muslimovic, D., Post, B., Speelman, J.D., Schmand, B., Cognitive profile of patients with newly diagnosed Parkinson's disease (2005) Neurology, 65, pp. 1239-1245 Aarsland, D., Bronnick, K., Williams-Gray, C., Mild cognitive impairment in Parkinson disease: a multicenter pooled analysis (2010) Neurology, 5, pp. 1062-1069 Pfeiffer, H.C., Løkkegaard, A., Zoetmulder, M., Cognitive impairment in early-stage non-demented Parkinson's disease patients (2014) Acta Neurol Scand, 129, pp. 307-318 Pavese, N., PET studies in Parkinson's disease motor and cognitive dysfunction (2012) Parkinsonism Relat Disord, 18, pp. S96-S99 Pappatà, S., Salvatore, E., Postiglione, A., In vivo imaging of neurotransmission and brain receptors in dementia (2008) J Neuroimaging, 18, pp. 111-124 Fitzpatrick, T., Mattis, P., Eidelberg, D., Functional imaging of cognitive impairment in Parkinson's disease (2010) Clin EEG Neurosci, 41, pp. 119-126 Muller, U., Wachter, T., Barthel, H., Striatal [123I] b-CIT SPECT and prefrontal cognitive functions in Parkinson's disease (2000) J Neural Transm, 107, pp. 303-319 Duchesne, N., Soucy, J.-P., Masson, H., Cognitive deficits and striatal dopaminergic denervation in Parkinson's disease: a single photon emission computed tomography study using 123Iodine-b-CIT in patients ON and OFF levodopa (2002) Clin Neuropharmacol, 25, pp. 216-224 Cropley, V.L., Fujita, M., Bara-Jimenez, W., Pre and post synaptic dopamine imaging and its relation with frontostriatal cognitive function in Parkinson's disease: PET studies with [11C]NNC 112 and [18F]FDOPA (2008) Psychiatry Res, 163, pp. 171-182 Weder, B.J., Leenders, K.L., Vontobel, P., Impaired somatosensory discrimination of shape in Parkinson's disease: association with caudate nucleus dopaminergic function (1999) Hum Brain Mapp, 8, pp. 1-12 Mariè, R.M., Barre, L., Dupuy, B., Relationships between striatal dopamine denervation and frontal executive tests in Parkinson's disease (1999) Neurosci Lett, 260, pp. 77-80 Rinne, J.O., Portin, R., Ruottinen, H., Cognitive impairment and the brain dopaminergic system in Parkinson disease: [18F]fluorodopa positron emission tomographic study (2000) Arch Neurol, 57, pp. 470-475 Jokinen, P., Bruck, A., Aalto, S., Impaired cognitive performance in Parkinson's disease is related to caudate dopaminergic hypofunction and hippocampal atrophy (2009) Parkinsonism Relat Disord, 15, pp. 88-93 Nobili, F., Campus, C., Arnaldi, D., Cognitive-nigrostriatal relationships in de novo, drug-naïve Parkinson's disease patients: a [I-123]FP-CIT study (2010) Mov Disord, 25, pp. 35-43 Holthoff, V.A., Vieregge, P., Kessler, J., Discordant twins with Parkinson's disease: positron emission tomography and early signs of impaired cognitive circuits (1994) Ann Neurol, 6, pp. 176-182 Emre, M., Aarsland, D., Brown, R., Clinical diagnostic criteria for dementia associated with Parkinson's disease (2007) Mov Disord, 22, pp. 1689-1707 Litvan, I., Goldman, J.G., Troster, A.I., Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force Guidelines (2012) Mov Disord, 27, pp. 349-356 Booij, J., Hemelaar, T.G., Speelman, J.D., One-day protocol for imaging of the nigrostriatal dopaminergic pathway in Parkinson's disease by [123]FPCIT SPECT (1999) J Nucl Med, 40, pp. 753-761 Varrone, A., Pellecchia, M.T., Amboni, M., Imaging of dopaminergic dysfunction with 123I-FP-CIT SPECT in early-onset parkin disease (2004) Neurology, 63, pp. 2097-2103 Polito, C., Berti, V., Ramat, S., Interaction of caudate dopamine depletion and brain metabolic changes with cognitive dysfunction in early Parkinson's disease (2012) Neurobiol Aging, 33, pp. 20629-20639 Kehagia, A.A., Barker, R.A., Robbins, T.W., Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson's disease (2010) Lancet Neurol, 9, pp. 1200-1213 Shen, L.H., Liao, M.H., Tseng, Y.C., Recent advances in imaging of dopaminergic neurons for evaluation of neuropsychiatric disorders (2012) J Biomed Biotechnol, 2012, p. 259349 Yamanaka, T., Ishii, F., Umemura, A., Temporary deterioration of executive function after subthalamic deep brain stimulation in Parkinson's disease (2012) Clin Neurol Neurosurg, 114, pp. 347-351 Paschali, A., Messinis, L., Kargiotis, O., SPECT neuroimaging and neuropsychological functions in different stages of Parkinson's disease (2010) Eur J Nucl Med Mol Imaging, 37, pp. 1128-1140 Brück, A., Portin, R., Lindell, A., Positron emission tomography shows that impaired frontal lobe functioning in Parkinson's disease is related to dopaminergic hypofunction in the caudate nucleus (2001) Neurosci Lett, 311, pp. 81-84 van Beilen, M., Portman, A.T., Kiers, H.A.L., Striatal FDOPA uptake and cognition in advanced non-demented Parkinson's disease: a clinical and FDOPA-PET study (2008) Parkinsonism Relat Disord, 14, pp. 224-228 Lozza, C., Baron, J.C., Eidelberg, D., Executive processes in Parkinson's disease: FDG-PET and network analysis (2004) Hum Brain Mapp, 22, pp. 236-245 Lebedev, A.V., Westman, E., Simmons, A., Large-scale resting state network correlates of cognitive impairment in Parkinson's disease and related dopaminergic deficits (2014) Front Syst Neurosci, 8, p. 45 Ekman, U., Eriksson, J., Forsgren, L., Functional brain activity and presynaptic dopamine uptake in patients with Parkinson's disease and mild cognitive impairment: a cross-sectional study (2012) Lancet Neurol, 11, pp. 679-687 Narayanan, N.S., Rodnitzky, R.L., Uc, E.Y., Prefrontal dopamine signaling and cognitive symptoms of Parkinson's Disease (2013) Rev Neurosci, 24, pp. 267-278 Christopher, L., Marras, C., Duff-Canning, S., Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson's disease with mild cognitive impairment (2014) Brain, 137, pp. 565-575 Petrou, M., Bohnen, N.I., Muller, M.L., Aβ-amyloid deposition in patients with Parkinson disease at risk for development of dementia (2012) Neurology, 79, pp. 1161-1167 Gomperts, S.N., Locascio, J.J., Rents, D., Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia (2013) Neurology, 80, pp. 85-91}, document_type={Journal Article, Abstract, Conference, }, affiliation={Center for Neurodegenerative Diseases, University of Salerno, Salerno, Italy. Department of Neurological Sciences, University Federico II, Naples, Italy Department of Psychology, Neuropsychology Laboratory, Second University of Naples, Caserta, Italy IDC Hermitage-Capodimonte, Naples, Italy University Parthenope, Naples, Italy Institute of Biostructure and Bioimaging, CNR, Naples, Italy Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_52065, author={Salvatore E, Tedeschi E, Mollica C, Vicidomini C, Varrone A, Coda ARD, Brunetti A, Salvatore M, De Michele G, Filla A, Pappata S}, title={Supratentorial and infratentorial damage in spinocerebellar ataxia 2: a diffusion-weighted MRI study}, date={2014 May}, journal={Mov Disord (ISSN: 0885-3185, 1531-8257, 0885-3185linking)}, year={2014}, fullvolume={343}, volume={343}, pages={780--786}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84899937472&partnerID=40&md5=a8c23cc6caf4c8ce852b5f3c191e8aa6}, abstract={Spinocerebellar ataxia type 2 (SCA2) is an autosomal-dominant degenerative disorder that is neuropathologically characterized primarily by infratentorial damage, although less severe supratentorial involvement may contribute to the clinical manifestation. Diffusion-weighted imaging (DWI)-Magnetic Resonance Imaging (MRI) studies of SCA2 have enabled in vivo quantification of neurodegeneration in infratentorial regions, whereas supratentorial regions have been explored less thoroughly. We measured microstructural changes in both infratentorial and supratentorial regions in 13 SCA2 patients (9 men, 4 women; mean age, 50±12 years) and 15 controls (10 men, 5 women; mean age, 49±14 years) using DWI-MRI and correlated the DWI changes with disease severity and duration. Disease severity was evaluated using the International Cooperative Ataxia Rating Scale and the Inherited Ataxia Clinical Rating Scale. Cerebral diffusion trace ( D-) values were generated, and regions of interest (ROIs) and voxel-based analysis with Statistical Parametric Mapping (SPM) were used for data analysis. In SCA2 patients, ROI analysis and SPM confirmed significant increases in D- values in the pons, cerebellar white matter (CWM) and middle cerebellar peduncles. Moreover, SPM analysis revealed increased D- values in the right thalamus, bilateral temporal cortex/white matter, and motor cortex/pyramidal tract regions. Increased diffusivity in the frontal white matter (FWM) and the CWM was significantly correlated with ataxia severity. DWI-MRI revealed that both infratentorial and supratentorial microstructural changes may characterize SCA2 patients in the course of the disease and might contribute to the severity of the symptoms. © 2013 International Parkinson and Movement Disorder Society.}, keywords={Mri, Sca2, Diffusion-Weighted Imaging, Neurodegeneration, Spinocerebellar Ataxia, Adult, Article, Autosomal Dominant Disorder, Brain Atrophy, Cag Repeat, Cerebellum Vermis, Clinical Article, Controlled Study, Diffusion Weighted Imaging, Disease Duration, Disease Severity, Female, Gliosis, Human, In Vivo Study, Mesencephalon, Middle Cerebellar Peduncle, Nerve Degeneration, Pons, Priority Journal, Putamen, Pyramidal Sign, Pyramidal Tract, Spinocerebellar Ataxia Type 2, Spinocerebellar Degeneration, Temporal Cortex, Thalamus, White Matter, Brain Cortex, Case Control Study, Dura Mater, Middle Aged, Myelinated Nerve, Pathology, Case-Control Studies, Cerebral Cortex, Diffusion Magnetic Resonance Imaging, Nerve Fibers, Cerebellum Pathology, Cerebral Cortex Pathology, Dura Mater Pathology, Myelinated Pathology, Spinocerebellar Ataxias Diagnosis, }, references={Taroni, F., Di Donato, S., Pathways to motor incoordination: the inherited ataxias (2004) Nat Rev Neurosci., 5, pp. 641-65 Schöls, L., Bauer, P., Schmidt, T., Schulte, T., Riess, O., Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis (2004) Lancet Neurol., 3, pp. 291-304 Lastres-Becker, I., Rüb, U., Auburger, G., Spinocerebellar ataxia 2 (SCA2) (2008) Cerebellum., 7, pp. 115-124 Orozco, G., Estrada, R., Perry, T.L., Dominantly inherited olivopontocerebellar atrophy from eastern Cuba. Clinical, neuropathological, and biochemical findings (1989) J Neurol Sci., 93, pp. 37-50 Dürr, A., Smadja, D., Cancel, G., Autosomal dominant cerebellar ataxia type I Martinique (French West Indies). Clinical and neuropathological analysis of 53 patients from three unrelated SCA2 families (1995) Brain., 118, pp. 1573-1581 Estrada, R., Galarraga, J., Orozco, G., Nodarse, A., Auburger, G., Spinocerebellar ataxia 2 (SCA2): morphometric analyses in 11 autopsies (1999) Acta Neuropathol (Berl), 97, pp. 306-310 Mascalchi, M., Spinocerebellar ataxias (2008) Neurol Sci., 29, pp. S311-S313 Klockgether, T., Skalej, M., Wedekind, D., Autosomal dominant cerebellar ataxia type I. MRI-based volumetry of posterior fossa structures and basal ganglia in spinocerebellar ataxia types 1, 2 and 3 (1998) Brain., 121, pp. 1678-1693 Giuffrida, S., Saponara, R., Restivo, D.A., Supratentorial atrophy in spinocerebellar ataxia type 2: MRI study of 20 patients (1999) J Neurol., 246, pp. 383-388 Guerrini, L., Lolli, F., Ginestroni, A., Brainstem neuro-degeneration correlates with clinical dysfunction in SCA1 but not in SCA2. A quantitative volumetric, diffusion and proton spectroscopy MR study (2004) Brain., 127, pp. 1785-1795 Le Bihan, D., Mangin, J.F., Poupon, C., Diffusion tensor imaging: concepts and applications (2001) J Magn Reson Imaging., 134, pp. 534-546 Molko, N., Pappata, S., Mangin, J.F., Monitoring disease progression in CADASIL with diffusion magnetic resonance imaging: a study with whole brain histogram analysis (2002) Stroke., 33, pp. 2902-2908 Pellecchia, M.T., Barone, P., Vicidomini, C., Progression of striatal and extrastriatal degeneration in multiple system atrophy: a longitudinal diffusion-weighted MR study (2011) Mov Disord., 26, pp. 1303-1309 Mandelli, M.L., De Simone, T., Minati, L., Diffusion tensor imaging of spinocerebellar ataxias types 1 and 2 (2007) AJNR Am J Neuroradiol., 28, pp. 1996-2000 Guimaraes, R.P., D'Abreu, A., Yasuda, C.L., A multimodal evaluation of microstructural white matter damage in spinocerebellar ataxia type 3 (2013) Mov Disord., 28, pp. 1125-1132 Alcauter, S., Barrios, F.A., Díaz, R., Fernández-Ruiz, J., Gray and white matter alterations in spinocerebellar ataxia type 7: an in vivo DTI and VBM study (2011) Neuroimage., 55, pp. 1-7 Della Nave, R., Ginestroni, A., Tessa, C., Brain white matter damage in SCA1 and SCA2. An in vivo study using voxel-based morphometry, histogram analysis of mean diffusivity and tract-based spatial statistics (2008) Neuroimage., 43, pp. 10-19 Trouillas, P., Takayanagi, T., Hallet, M., International cooperative ataxia rating scale for pharmacological assessment of the cerebellar syndrome (1997) J Neurol Sci., 145, pp. 205-211 Folstein, M.F., Folstein, S.E., McHugh, P.R., "Mini-mental state." A practical method for grading the cognitive state of patients for the clinician (1975) J Psychiatr Res., 12, pp. 189-198 Filla, A., DeMichele, G., Caruso, G., Marconi, R., Campanella, G., Genetic data and natural history of Friedreich's disease: a study of 80 Italian patients (1990) J Neurol., 237, pp. 345-351 Filla, A., De Michele, G., Santoro, L., Spinocerebellar ataxia type 2 in southern Italy: a clinical and molecular study of 30 families (1999) J Neurol., 246, pp. 467-471 Schocke, M.F.H., Seppi, K., Esterhammer, R., Diffusion weighted MRI differentiates the Parkinson variant of multiple system atrophy from PD (2002) Neurology., 58, pp. 575-580 Brenneis, C., Boesch, S.M., Schocke, M., Wenning, G.K., Poewe, W., Atrophy pattern in SCA2 determined by voxel-based morphometry (2003) Neuroreport., 14, pp. 1799-1802 Della Nave, R., Foresti, S., Tessa, C., ADC mapping of neurodegeneration in the brainstem and cerebellum of patients with progressive ataxias (2004) Neuroimage., 22, pp. 698-705 D'Agata, F., Caroppo, P., Boghi, A., Linking coordinative and executive dysfunctions to atrophy in spinocerebellar ataxia 2 patients (2011) Brain Struct Funct ., 216, pp. 275-288 Iwabuchi, K., Tsuchiya, K., Uchihara, T., Yagishita, S., Autosomal dominant spinocerebellar degenerations. Clinical, pathological, and genetic correlations (1999) Rev Neurol (Paris)., 155, pp. 250-270 Hoche, F., Balikó, L., den Dunnen, W., Spinocerebellar ataxia type 2 (SCA2): identification of early brain degeneration in one monozygous twin in the initial disease stage (2011) Cerebellum., 10, pp. 245-253 Goel, G., Pal, P.K., Ravishankar, S., Gray matter volume deficits in spinocerebellar ataxia: an optimized voxel based morphometric study (2011) Parkinsonism Relat Disord., 7, pp. 521-527 Ying, S.H., Choi, S.I., Perlman, S.L., Baloh, R.W., Zee, D.S., Toga, A.W., Pontine and cerebellar atrophy correlate with clinical disability in SCA2 (2006) Neurology., 66, pp. 424-426. , 14 Jung, B.C., Choi, S.I., Du, A.X., MRI shows a region-specific pattern of atrophy in spinocerebellar ataxia type 2 (2012) Cerebellum., 11, pp. 272-279 Saute, J.A., Donis, K.C., Serrano-Munuera, C., Ataxia rating scales-psychometric profiles, natural history and their application in clinical trials (2012) Cerebellum., 11, pp. 488-504 Murdoch, B.E., The cerebellum and language: historical perspective and review (2010) Cortex., 46, pp. 858-868 Burk, K., Globas, C., Bosch, S., Cognitive deficits in spinocerebellar ataxia 2 (1999) Brain., 122, pp. 769-777 Assaf, Y., Can we use diffusion MRI as a bio-marker of neurodegenerative processes? (2008) Bioessays, 30, pp. 1235-1245}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Italy. Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy Institute of Biostructure and Bioimaging, CNR, Naples, Italy IRCCS Fondazione SDN, Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_11391, author={Vicidomini C, Vinciguerra A, Greco A, Panico M, Gargiulo S, Gramanzini M, Coda ARD, Pignataro G, Quarantelli M, Tavitian B, Dollé F, Brunetti A, Salvatore M, Annunziato L, Pappata S}, title={Imaging of brain TSPO expression in a mouse model of stroke with [18F]DPA-714 and micro-PET}, date={2013 Oct}, journal={Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997)}, year={2013}, fullvolume={307}, volume={307}, pages={450--450}, url={}, abstract={}, keywords={, }, references={}, document_type={Abstract, Conference, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_52090, author={Erro R, Barone P, Vicidomini C, Picillo M, Pappata S}, title={Patients with Parkinson's disease and scans with (predominant) ipsilateral dopaminergic deficit}, date={2013 Sep}, journal={J Neurol (ISSN: 0340-5354, 1432-1459, 1432-1459electronic)}, year={2013}, fullvolume={332}, volume={332}, pages={2405--2406}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84884355756&partnerID=40&md5=0863541b77e160ce9f774cf7949a5e11}, abstract={}, keywords={Iodine 123, Bradykinesia, Brain Cell, Brain Depth Stimulation, Corpus Striatum, Human, Letter, Motor Dysfunction, Nonhuman, Parkinson Disease, Priority Journal, Radiological Parameters, Rest Tremor, Scans With Ipsilateral Dopaminergic Deficit, Single Photon Emission Computer Tomography, Aged, Dopamine Plasma Membrane Transport Proteins, Functional Laterality, Iodine Radioisotopes, Middle Aged, Emission-Computed, Single-Photon, Tropanes, Brain Radionuclide Imaging, Dopamine Deficiency, Dopamine Plasma Membrane Transport Proteins Analysis Metabolism, Functional Laterality Physiology, Iodine Radioisotopes Diagnostic Use, Parkinson Disease Complications Metabolism Radionuclide Imaging, Rest Physiology, Tremor Etiology Radionuclide Imaging, Tropanes Diagnostic Use, }, references={Aguirregomozcorta, M., Stamelou, M., Antonini, A., Schwingenschuh, P., Prvulovich, L., Edwards, M.J., Dickson, J.C., Bhatia, K.P., Patients with rest-tremor and scans with ipsilateral dopaminergic deficit (2013) J Neurol, 260, pp. 1132-1135. , 23196338 10.1007/s00415-012-6774- Erro, R., Pappatà, S., Amboni, M., Vicidomini, C., Longo, K., Santangelo, G., Anxiety is associated with striatal dopamine transporter availability in newly diagnosed untreated Parkinson's disease patients (2012) Parkinsonism Relat Disord, 18, pp. 1034-1038. , 22789824 10.1016/j.parkreldis.2012.05.022 Spiegel, J., Hellwig, D., Samnick, S., Jost, W., Mollers, M.O., Fassbender, K., Kirsch, C.M., Dillmann, U., Striatal FP-CIT uptake differs in the subtypes of early Parkinson's disease (2007) J Neural Transm, 114, pp. 331-335. , 16715205 10.1007/s00702-006-0518-2 1:STN:280:DC%2BD2s7htlWrsA%3D%3D Gerfen, C.R., Staines, W.A., Arbuthnott, G.W., Fibiger, H.C., Crossed connections of the substantia nigra in the rat (1982) J Comp Neurol, 207, pp. 283-303. , 7107988 10.1002/cne.902070308 1:STN:280:DyaL383ms1Ckug%3D%3D Hazrati, L.N., Parent, A., Contralateral pallidothalamic and pallidotegmental projections in primates: An anterograde and retrograde labeling study (1991) Brain Res, 567, pp. 212-223. , 1817727 10.1016/0006-8993(91)90798-Z 1:STN:280:DyaK383ovVOhsw%3D%3D Ilinsky, I.A., Kultas-Ilinsky, K., Rosina, A., Haddy, M., Quantitative evaluation of crossed and uncrossed projections from basal ganglia and cerebellum to the cat thalamus (1987) Neuroscience, 21, pp. 207-227. , 3601076 10.1016/0306-4522(87)90334-4 1:STN:280:DyaL2s3lvVOlsA%3D%3D Shemisa, K., Hass, C.J., Foote, K.D., Okun, M.S., Wu, S.S., Jacobson IV, C.E., Dai, Y., Fernandez, H.H., Unilateral deep brain stimulation surgery in Parkinson's disease improves ipsilateral symptoms regardless of laterality (2011) Parkinsonism Relat Disord, 17, pp. 745-748. , 21856205 10.1016/j.parkreldis.2011.07.010 Parent, A., Hazrati, L.-N., Functional anatomy of the basal ganglia. I. The corticobasal ganglia-thalamo-cortical loop (1995) Brain Res Rev, 20, pp. 91-127. , 7711769 10.1016/0165-0173(94)00007-C 1:STN:280:DyaK2M3islaisA%3D%3D Kumar, R., Lozano, A.M., Sime, E., Halket, E., Lang, A.E., Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation (1995) Neurology, 53, pp. 561-566. , 10.1212/WNL.53.3.561 Kojovic, M., Bologna, M., Kassavetis, P., Murase, N., Palomar, F.J., Berardelli, A., Rothwell, J.C., Bhatia, K.P., Functional reorganization of sensorimotor cortex in early Parkinson disease (2012) Neurology, 78, pp. 1441-1448. , 22517098 10.1212/WNL.0b013e318253d5dd 1:STN:280:DC%2BC38rmsVCgsg%3D%3D}, document_type={Letter, Journal Article, }, affiliation={Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, UCL, Queen Square, London WC1N 3BG, United Kingdom Center for Neurodegenerative Diseases-CEMAND, University of Salerno, Salerno, Italy Institute of Biostructure and Bioimaging, CNR, Naples, Italy Department of Neurological Science, University Federico II, Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_10267, author={Erro R, Pappata S, Amboni M, Vicidomini C, Longo K, Santangelo G, Picillo M, Vitale C, Moccia M, Giordano F, Brunetti A, Pellecchia MT, Salvatore M, Barone P}, title={Anxiety is associated with striatal dopamine transporter availability in newly diagnosed untreated Parkinson's disease patients}, date={2012 Nov}, journal={Parkinsonism Relat D (ISSN: 1873-5126, 1353-8020, 1873-5126electronic)}, year={2012}, fullvolume={465}, volume={465}, pages={1034--1038}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84869099099&partnerID=40&md5=39d13f9a9d31eb2f941b6af3787ad300}, abstract={BACKGROUND: Anxiety is a common non-motor symptom among patients with Parkinson's disease (PD). Although the etiology of anxiety in PD is likely to be multifactorial, a dysfunction in the dopaminergic system might be implicated in its pathogenesis. The aim of our study was to investigate a possible dopaminergic mechanism involved in anxiety in newly diagnosed never-medicated PD patients using SPECT and I-FP-CIT as the dopamine transporter ligand.; METHODS: Thirty-four newly diagnosed, untreated PD patients with asymmetric motor symptoms were included in the study: 17 patients with right- and 17 with left-motor onset, matched for age, disease duration and motor disability constituted the group. They were all evaluated for anxiety and depression and underwent an SPECT with I-FP-CIT. Dopamine transporter (DAT) availability values for right and left caudate and putamen were calculated and compared between patients with and without anxiety. Regression analyses were also performed in order to correlate DAT availability with the severity of the anxiety symptoms.; RESULTS: Comparison between PD patients with and those without anxiety revealed significant differences of DAT availability in all the examined regions except the right putamen. In the group of patients considered as a whole, a significant correlation was found between increased anxiety severity and decreased DAT availability in right caudate.; CONCLUSIONS: We reported an association between nigrostriatal DAT availability deficits and anxiety symptoms in newly diagnosed, untreated PD patients. Our results suggest that hypofunction of the nigrostriatal dopaminergic system may represent one of the functional anomalies involved in anxiety in PD from the earliest stages of disease and irrespective of any therapy. 2012 Elsevier Ltd. All rights reserved.}, keywords={123-I-Fp-Cit Spect, Anxiety, De Novo, Dopamine Transporter, Mood, Parkinson, S Disease, Fp Cit I 123, Radiopharmaceutical Agent, Unclassified Drug, Adult, Anxiety Disorder, Article, Bioavailability, Caudate Nucleus, Clinical Article, Controlled Study, Disease Severity, Female, Human, Nigroneostriatal System, Parkinson Disease, Priority Journal, Putamen, Single Photon Emission Computer Tomography, Case-Control Studies, Corpus Striatum, Dopamine Plasma Membrane Transport Proteins, Follow-Up Studies, Functional Laterality, Middle Aged, Psychiatric Status Rating Scales, Regression Analysis, Severity Of Illness Index, Emission-Computed, Single-Photon, Tropanes, }, references={Riedel, O., Klotsche, J., Spottke, A., Deuschl, G., Förstl, Henn, F., Frequency of dementia, depression, and other neuropsychiatric symptoms in 1449 outpatients with Parkinson's disease (2010) J Neurol, 257, pp. 1073-108 Dissanayaka, N.N.W., Sellbach, A., Matheson, S., O'Sullivan, J.D., Silburn, P.A., Byrne, G.J., Anxiety disorders in Parkinson's disease: prevalence and risk factors (2010) Mov Disord, 25 (7), pp. 838-845 Leentjens, A.F.G., Dujardin, K., Marsh, L., Martinez-Martin, P., Richard, I.H., Starkstein, S.E., Symptomatology and markers of anxiety disorders in Parkinson's disease: a cross-sectional study (2011) Mov Disord, 26 (3), pp. 484-492 Pontone, G.M., Williams, J.R., Anderson, K.E., Chase, G., Goldstein, S.R., Grill, S., Anxiety and self-perceived health status in Parkinson's disease (2011) Parkinsonism and Relat Disord, 17, pp. 249-254 Siemers, E.R., Shekhar, A., Quaid, K., Dickson, H., Anxiety and motor performance in Parkinson's disease (1993) Mov Disord, 8, pp. 501-506 Vazquez, A., Jimenez-Jimenez, F.J., Garcia-Ruiz, P., Garcia-Urra, D., " Panic attacks" in Parkinson's disease. A long-term complication of levodopa therapy (1993) Acta Neurol Scand, 87, pp. 14-18 Lauterbach, E.C., Freeman, A., Vogel, R.L., Correlates of generalized anxiety and panic attacks in dystonia and Parkinson's disease (2003) Cogn Behav Neurol, 16, pp. 225-233 Henderson, R., Kurlan, R., Kersun, J.M., Como, P., Preliminary examination of anxiety and depression in Parkinson's disease (1992) J Neuropsychiatry Clin Neurosci, 4, pp. 257-264 Maricle, R.A., Nutt, J.G., Valentine, R.J., Carter, J.H., Dose-response relationship of levodopa with mood and anxiety in fluctuating Parkinson's disease: a double- blind, placebo-controlled study (1995) Neurology, 45, pp. 1757-1760 Davidson, R.J., Anxiety and affective style. Role of prefrontal cortex and amygdala (2002) Biol Psychiatry, 51, pp. 68-80 Kaasinen, V., Nurmi, E., Bergman, J., Eskola, O., Sollin, O., Sonninen, P., Personality traits and brain dopaminergic function in Parkinson's disease (2001) Proc Natl Acad Sci USA, 98, pp. 13272-13277 Weintraub, D., Newberg, A.B., Cary, M.S., Siderowf, A.D., Moberg, P.J., Kleiner-Fismn, G., Striatal dopamine transporter imaging correlates with anxiety and depression symptoms in Parkinson's disease (2005) J Nucl Med, 46, pp. 227-232 Moriyama, T.S., Felicio, A.C., Chagas, M.H.N., Tardelli, V.S., Ferraz, H.B., Tumas, V., Increased dopamine transporter density in Parkinson's disease patients with social anxiety disorder (2011) J Neurol Sci, 310, pp. 53-57 Sossi, V., de la Fuente-Fernandez, R., Schulzer, M., Troiano, A.R., Ruth, T.J., Stoessl, A.J., Dopamine transporter relation to dopamine turnover in Parkinson's disease: a positron emission tomography study (2007) Ann Neurol, 62 (5), pp. 468-474 Pappatà, S., Santangelo, G., Aarsland, D., Vicidomini, C., Longo, K., Bronnick, K., Mild cognitive impairment in drug-naive patients with PD is associated with cerebral hypometabolism (2011) Neurology, 77 (14), pp. 1357-1362 Fahn, S., Elton, R.L., Unified Parkinson's disease rating scale (1987) Recent developments in Parkinson's disease, 2, pp. 153-163. , UPDRS program members Macmillan Healthcare information, Florham Park. NJ Booij, J., Hemelaar, T.G., Speelman, J.D., de Bruin, K., Janssen, A.G., van Royen, E.A., One-day protocol for imaging of the nigrostriatal dopaminergic pathway in Parkinson's disease by [123]FPCIT SPECT (1999) J Nucl Med, 40 (5), pp. 753-761 Varrone, A., Pellecchia, M.T., Amboni, M., Sansone, V., Salvatore, E., Ghezzi, D., Imaging of dopaminergic dysfunction with 123I-FP-CIT SPECT in early-onset parkin disease (2004) Neurology, 63 (11), pp. 2097-2103 Kaasinen, V., Rinne, J.O., Functional imaging studies of dopamine system and cognition in normal aging and Parkinson's disease (2002) Neurosci Biobehav Rev, 26, pp. 785-793 Muller, U., Wachter, T., Barthel, H., Reuter, M., von Cramon, D.Y., Striatal [123I]beta-CIT SPECT and prefrontal cognitive functions in Parkinson's disease (2000) J Neural Transm, 107 (3), pp. 303-319 Rektorova, I., Srovnalova, H., Kubikova, R., Prasek, J., Striatal dopamine transporter imaging correlates with depressive symptoms and Tower of London task performance in Parkinson's disease (2008) Mov Disord, 23 (11), pp. 1580-1587 Qiu, C., Liao, W., Ding, J., Feng, Y., Zhu, C., Nie, X., Regional homogeneity changes in social anxiety disorder: a resting-state fMRI study (2011) Psychiatry Res, 194 (1), pp. 47-53 Foster, P.S., Drago, V., Crucian, G.P., Sullivan, W.K., Rhodes, R.D., Shenal, B.V., Anxiety and depression severity are related to right but not left onset Parkinson's disease duration (2011) J Neurol Sci, 305, pp. 131-135 Koerts, J., Leenders, K.L., Koning, M., Portman, A.T., van Beilen, M., Striatal dopaminergic activity (FDOPA-PET) associated with cognitive items of a depression scale (MADRS) in Parkinson's disease (2007) Eur J Neurosci, 25, pp. 3132-3136 Barone, P., Poewe, W., Albrecht, S., Debleuvre, C., Massey, D., Rascol, O., Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled trial (2010) Lancet Neurol, 9 (6), pp. 573-580 Kano, O., Ikeda, K., Cridebring, D., Takazawa, T., Yoshii, Y., Iwasaki, Y., Neurobiology of depression and anxiety in Parkinson's disease (2011) Parkinsons Dis, , Published online Jaunarajs, K.L.E., Angoa-Perez, M., Kuhn, D.M., Bishop, C., Potential mechanisms underlying anxiety and depression in Parkinson's disease: consequences of l-DOPA treatment (2011) Neurosci Biobehav Rev, 35 (3), pp. 556-564 Ziebell, M., Holm-Hansen, S., Thomsen, G., Wagner, G., Jensen, P., Pinborg, L.H., Serotonin transporters in dopamine transporter imaging: a head-to-head comparison of dopamine transporter SPECT radioligands 123I-FP-CIT and 123I-PE2I (2010) J Nucl Med, 51 (12), pp. 1885-1891 Booij, J., de Jong, J., de Bruin, K., Knol, R., de Win, M.M., van Eck-Smit, B.L., Quantification of striatal dopamine transporters with 123I-FP-CIT SPECT is influenced by the selective serotonin reuptake inhibitor paroxetine: a double-blind, placebo controlled, crossover study in healthy control subjects (2007) J Nucl Med, 48 (3), pp. 359-366 Beucke, J.C., Plotkin, M., Winter, C., Endrass, T., Amthauer, H., Juckel, G., Midbrain serotonin transporters in de novo and L-DOPA-treated patients with early Parkinson's disease-a [123 I]-ADAM SPECT study (2011) Eur J Neurol, 18 (5), pp. 750-755 Strecker, K., Wegner, F., Hesse, S., Becker, G.A., Patt, M., Meyer, P.M., Preserved serotonin transporter binding in de novo Parkinson's disease: negative correlation with the dopamine transporter (2011) J Neurol, 258 (1), pp. 19-26. , Epub 2010 Jul 21 Bower, J.H., Grossardt, B.R., Maraganore, D.M., Ahlskog, J.E., Colligan, R.C., Geda, Y.E., Anxious personality predicts an increased risk of Parkinson's disease (2010) Mov Disord, 25 (13), pp. 2105-2113 Bogdanova, Y., Cronin-Golomb, A., Neurocognitive correlates of apathy and anxiety in Parkinson's disease (2012) Parkinsons Dis, , Published online}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={University Federico II, Department of Neurological Science, Naples, Italy. Institute of Biostructure and Bioimaging, CNR, Naples, Italy IDC Hermitage - Capodimonte, Italy Neuropsychology Laboratory, Department of Psychology, Second University of Naples, Caserta, Italy University Parthenope, Naples, Italy University of Salerno, Center for neurodegenerative diseases - CEMAND, Via S. Allende, 84081 Baronissi (SA), Italy}, ibbaffiliation={1}, } @article{IBB_ID_50713, author={Pappata S, Santangelo G, Aarsland D, Vicidomini C, Longo K, Bronnick K, Amboni M, Erro R, Vitale C, Caprio MG, Pellecchia MT, Brunetti A, De Michele G, Salvatore M, Barone P}, title={Mild cognitive impairment in drug-naive patients with PD is associated with cerebral hypometabolism}, date={2011 Oct 4}, journal={Neurology (ISSN: 0028-3878, 1526-632x, 1526-632xelectronic)}, year={2011}, fullvolume={445}, volume={445}, pages={1357--1362}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-82255170755&partnerID=40&md5=5436acf269f0e166cb1c08daa1e5e3d0}, abstract={Objective: To characterize brain metabolic changes associated with mild cognitive impairment (MCI) in drug-naive patients with Parkinson disease (PD) using 18F-fluorodeoxyglucose (FDG) and PET (FDG-PET). Methods: This cross-sectional study included newly diagnosed patients with PD with MCI in single or multiple domain (PD-MCI; n = 12) and without MCI (PD-nMCI; n = 12), and healthy controls (n = 12). The groups were matched for age. Moreover, the patient groups were matched for motor disability. All subjects underwent a FDG-PET study. Cerebral regional relative metabolic maps were compared in PD-MCI, PD-nMCI, and controls using regions of interest analysis (ROIs) and voxel-based analysis with statistical parametric mapping. Results: ROIs and voxel-based analyses revealed significant relative hypometabolism in the prefrontal, superior/inferior parietal, and associative occipital cortices as well as in the striatum in patients with PD-MCI relative to controls (p = 0.05) and to a lesser extent in patients with PD-nMCI. In contrast, patients with PD-nMCI did not show significant metabolic changes as compared to controls. Conclusion: MCI in patients with PD is associated with cortical hypometabolism since the earliest stage, independent of therapy or motor disability. The early involvement of posterior cortical region, a pattern shared by advanced stages of PD-MCI and PD with dementia, could represent an early marker of dementia. The relevance of this pattern in predicting prodromal dementia has to be evaluated in longitudinal studies. © 2011 by AAN Enterprises, Inc.}, keywords={Fluorodeoxyglucose F 18, Diagnostic Agent, Adult, Article, Brain Disease, Brain Mapping, Brain Metabolism, Cerebral Hypometabolism, Clinical Article, Controlled Study, Corpus Striatum, Cross-Sectional Study, Disease Association, Female, Human, Mild Cognitive Impairment, Neuroimaging, Occipital Cortex, Parietal Cortex, Parkinson Disease, Positron Emission Tomography, Priority Journal, Analysis Of Variance, Brain Cortex, Case Control Study, Chi Square Distribution, Cognitive Defect, Follow Up, Middle Aged, Neuropsychological Test, Scintiscanning, Case-Control Studies, Cerebral Cortex, Chi-Square Distribution, Cognition Disorders, Follow-Up Studies, Positron-Emission Tomography, Radionuclide Imaging, Etiology, Diagnostic Use, Complications, }, references={Williams-Gray, C.H., Foltynie, T., Brayne, C.E.G., Robbins, T.W., Barker, R.A., Evolution of cognitive dysfunction in an incident Parkinson's disease cohort (2007) Brain, 130 (7), pp. 1787-1798. , DOI 10.1093/brain/awm11 Muslimovic, D., Post, B., Speelman, J.D., Schmand, B., Cognitive profile of patients with newly diagnosed Parkinson disease (2005) Neurology, 65 (8), pp. 1239-1245. , DOI 10.1212/01.wnl.0000180516.69442.95 Aarsland, D., Brønnick, K., Larsen, J.P., Cognitive impairment in incident, untreated Parkinson disease: The Norwegian ParkWest study (2009) Neurology, 72, pp. 1121-1126 Janvin, C.C., Larsen, J.P., Aarsland, D., Hugdahl, K., Subtypes of mild cognitive impairment in Parkinson's disease: Progression to dementia (2006) Movement Disorders, 21 (9), pp. 1343-1349. , DOI 10.1002/mds.20974 Huang, C., Mattis, P., Perrine, K., Brown, N., Dhawan, V., Eidelberg, D., Metabolic abnormalities associated with mild cognitive impairment in Parkinson disease (2008) Neurology, 70 (16 PART 2), pp. 1470-1477. , DOI 10.1212/01.wnl.0000304050.05332.9c, PII 0000611420080415100017 Hosokai, Y., Nishio, Y., Hirayama, K., Distinct patterns of regional cerebral glucose metabolism in Parkinson's disease with and without mild cognitive impairment (2009) Mov Disord, 24, pp. 854-862 Borghammer, P., Chakravarty, M., Jonsdottir, K.Y., Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: Probably even at early disease stages Brain Struct Funct, 2010 (214), pp. 303-317 Berding, G., Odin, P., Brooks, D.J., Nikkhah, G., Matthies, C., Peschel, T., Shing, M., Knapp, W.H., Resting regional cerebral glucose metabolism in advanced Parkinson's disease studied in the off and on conditions with [18F]FDG-PET (2001) Movement Disorders, 16 (6), pp. 1014-1022. , DOI 10.1002/mds.1212 Feigin, A., Fukuda, M., Dhawan, V., Przedborski, S., Jackson-Lewis, V., Mentis, M.J., Moeller, J.R., Eidelberg, D., Metabolic correlates of levodopa response in Parkinson's disease (2001) Neurology, 57 (11), pp. 2083-2088 Hirano, S., Asanuma, K., Ma, Y., Dissociation of metabolic and neurovascular responses to levodopa in the treatment of Parkinson's disease (2008) J Neurosci, 28, pp. 4201-4209 Hughes, A.J., Daniel, S.E., Kilford, L., Lees, A.J., Accuracy of clinical diagnosis of idiopathic Parkinson's Disease: A clinic-pathological study of 100 cases (1992) J Neurol Neurosurg Psychiatry, 55, pp. 181-184 Emre, M., Aarsland, D., Brown, R., Burn, D.J., Duyckaerts, C., Mizuno, Y., Broe, G.A., Dubois, B., Clinical diagnostic criteria for dementia associated with Parkinson's disease (2007) Movement Disorders, 22 (12), pp. 1689-1707. , DOI 10.1002/mds.21507 Aarsland, D., Bronnick, K., Williams-Gray, C., Mild cognitive impairment in Parkinson disease: A multicenter pooled analysis Neurology, 2010 (75), pp. 1062-1069 Pappatà, S., Varrone, A., Vicidomini, C., SPECT imaging of GABA(A)/benzodiazepine receptors and cerebral perfusion in mild cognitive impairment (2010) Eur J Nucl Med Mol Imaging, 37, pp. 1156-1163 Borghammer, P., Cumming, P., Aanerud, J., Gjedde, A., Artefactual subcortical hyperperfusion in PET studies normalized to global mean: Lessons from Parkinson's disease (2009) Neuroimage, 45, pp. 249-257 Nobili, F., Abbruzzese, G., Morbelli, S., Amnestic mild cognitive impairment in Parkinson's disease: A brain perfusion SPECT study (2009) Mov Disord, 24, pp. 414-421 Huang, C., Tang, C., Feigin, A., Lesser, M., Ma, Y., Pourfar, M., Dhawan, V., Eidelberg, D., Changes in network activity with the progression of Parkinson's disease (2007) Brain, 130 (7), pp. 1834-1846. , DOI 10.1093/brain/awm086 Klein, J.C., Eggers, C., Kalbe, E., Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo Neurology, 2010 (74), pp. 885-892 Berti, V., Polito, C., Ramat, S., Brain metabolic correlates of dopaminergic degeneration in de novo idiopathic Parkinson's disease (2010) Eur J Nucl Med Mol Imaging, 37, pp. 537-544 Polito, C., Berti, V., Ramat, S., Interaction of caudate dopamine depletion and brain metabolic changes with cognitive dysfunction in early Parkinson's disease (2010) Neurobiol Aging Epub Shimada, H., Hirano, S., Shinotoh, H., Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET (2009) Neurology, 73, pp. 273-278 Ferrer, I., Martinez, A., Blanco, R., Dalfó, E., Carmona, M., Neuropathology of sporadic Parkinson disease before the appearance of parkinsonism: Preclinical Parkinson disease (2011) J Neural Transm, 118, pp. 821-839 Braak, H., Del Tredici, K., Rub, U., De Vos, R.A.I., Jansen Steur, E.N.H., Braak, E., Staging of brain pathology related to sporadic Parkinson's disease (2003) Neurobiology of Aging, 24 (2), pp. 197-211. , DOI 10.1016/S0197-4580(02)00065-9, PII S0197458002000659 Apostolova, L.G., Beyer, M., Green, A.E., Hippocampal, caudate, and ventricular changes in Parkinson's disease with and without dementia Mov Disord, 2010 (25), pp. 687-688 Van Laere, K., Santens, P., Bosman, T., De Reuck, J., Mortelmans, L., Dierckx, R., Statistical parametric mapping of 99mTc-ECD SPECT in idiopathic Parkinson's disease and multiple system atrophy with predominant parkinsonian features: Correlation with clinical parameters (2004) Journal of Nuclear Medicine, 45 (6), pp. 933-942. , http://jnm.snmjournals.org/cgi/reprint/45/6/933 Williams-Gray, C. H., Foltynie, T., Brayne, C. E. G., Robbins, T. W., Barker, R. A., Evolution of cognitive dysfunction in an incident Parkinson's disease cohort (2007) Brain, 130 (7), pp. 1787-1798. , DOI 10. 1093/brain/awm11 Aarsland, D., Br nnick, K., Larsen, J. P., Cognitive impairment in incident, untreated Parkinson disease: The Norwegian ParkWest study (2009) Neurology, 72, pp. 1121-1126 Janvin, C. C., Larsen, J. P., Aarsland, D., Hugdahl, K., Subtypes of mild cognitive impairment in Parkinson's disease: Progression to dementia (2006) Movement Disorders, 21 (9), pp. 1343-1349. , DOI 10. 1002/mds. 20974 Hughes, A. J., Daniel, S. E., Kilford, L., Lees, A. J., Accuracy of clinical diagnosis of idiopathic Parkinson's Disease: A clinic-pathological study of 100 cases (1992) J Neurol Neurosurg Psychiatry, 55, pp. 181-184 Pappat, S., Varrone, A., Vicidomini, C., SPECT imaging of GABA (A) /benzodiazepine receptors and cerebral perfusion in mild cognitive impairment (2010) Eur J Nucl Med Mol Imaging, 37, pp. 1156-1163 Klein, J. C., Eggers, C., Kalbe, E., Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo Neurology, 2010 (74), pp. 885-892 Apostolova, L. G., Beyer, M., Green, A. E., Hippocampal, caudate, and ventricular changes in Parkinson's disease with and without dementia Mov Disord, 2010 (25), pp. 687-688}, document_type={Journal Article, }, affiliation={Institute of Biostructure and Bioimaging, CNR, Via Pansini 5, Edificio 10, 80131, Naples, Italy Department of Psychology, Second University of Naples, Caserta, Italy IDC Hermitage Capodimonte, Naples, Italy Departments of Neurological Sciences, University Federico II, Naples, Italy Departments of Biomorphological Sciences, University Federico II, Naples, Italy Psychiatric Division (D.A., K.B.), Stavanger University Hospital, University of Oslo, Oslo, Norway University Parthenope, Naples, Italy Centro Regionale, Schola Medica Salernitana, University of Salerno, Italy}, ibbaffiliation={1}, } @article{IBB_ID_11324, author={Milite C, Castellano S, Benedetti R, Tosco A, Ciliberti C, Vicidomini C, Boully L, Franci G, Altucci L, Mai A, Sbardella G}, title={Modulation of the activity of histone acetyltransferases by long chain alkylidenemalonates (LoCAMs)}, date={2011 Jun 15}, journal={Bioorg Med Chem (ISSN: 0968-0896, 1464-3391, 1464-3391electronic)}, year={2011}, fullvolume={327}, volume={327}, pages={3690--3701}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79958265044&partnerID=40&md5=60b1cedc8aacbaba9aa0db197b88db75}, abstract={A novel class of KAT modulators (long chain alkylidenemalonates, LoCAMs) has been identified. Variations of the alkyl chain length can change the activity profile from inhibition of both KAT3A/KAT2B (as derivative 2a) to the peculiar profile of pentadecylidenemalonate 1b, the first activator/inhibitor of histone acetyltransferases. Together with the powerful apoptotic effect (particularly notable if considering that anacardic acid and other KAT inhibitors are not cell permeable) appoint them as valuable biological tools to understand the mechanisms of lysine acetyltransferases. (C) 2011 Elsevier Ltd. All rights reserved.}, keywords={Epigenetics, Histone Acetyltransferases Modulators, Kat, P300 Cbp, Pcaf Activator, 2 Dodecylmalonic Acid, 2 Tridecylmalonic Acid, 2 Undecylmalonic Acid, 2 Dimethyl 5 Pentadecyl 1, 3 Dioxane 4, 6 Dione, 2 Dimethyl 5 Pentadecylidene 1, Alkan 2 Ylidene Malonic Acid Derivative, Diethyl 2 (1 Aminopentadecylidene)malonic Acid, Diethyl 2 (1 Chloropentadecylidene)malonic Acid, Diethyl 2 (1 Hydroxyheptadecylidene)malonic Acid, Diethyl 2 (1 Hydroxyhexadecylidene)malonic Acid, Diethyl 2 (1 Hydroxypentadecylidene)malonic Acid, Diethyl 2 [(tridecylamino)methylene]malonic Acid Derivative, Diethyl 2 Pentadecylidenemalonic Acid, Diethyl 2 Tetradecylidenemalonic Acid, Diethyl 2 Tridecylmalonic Acid, Enzyme Inhibitor, Functional Group, Long Chain Alkylidenemalonic Acid Derivative, Myristyl Aldehyde, Pentadecanal, Pentadecylmalonic Acid, Tetradecylmalonic Acid, Unclassified Drug, Apoptosis, Article, Biological Activity, Cancer Cell, Cell Cycle, Concentration Response, Controlled Study, Drug Synthesis, Enzyme Activity, Enzyme Induction, Enzyme Inhibition, Enzyme Mechanism, Enzyme Regulation, Histone Acetylation, Human, Human Cell, Leukemia Cell, Protein Expression, Protein Interaction, Protein Modification, Protein Purification, Rigidity, Structure Activity Relation, Alkylation, Blotting, Western, Cell Line, Tumor, Enzyme Activation, Malonates, U937 Cells, Diethyl 2 (1 Aminopentadecylidene) Malonic Acid, Diethyl 2 (1 Chloropentadecylidene) Malonic Acid, Diethyl 2 (1 Hydroxyheptadecylidene) Malonic Acid, Diethyl 2 (1 Hydroxyhexadecylidene) Malonic Acid, Diethyl 2 (1 Hydroxypentadecylidene) Malonic Acid, Diethyl 2 [(tridecylamino) Methylene] Malonic Acid Derivative, }, references={Kouzarides, T., (2007) Cell, 128, p. 69 Berger, S.L., (2007) Nature, 447, p. 407 Ruthenburg, A.J., Li, H., Patel, D.J., Allis, C.D., (2007) Nat. Rev. Mol. Cell Biol., 8, p. 983 Strahl, B.D., Allis, C.D., (2000) Nature, 403, p. 41 Allfrey, V.G., Faulkner, R., Mirsky, A.E., (1964) Proc. Natl. Acad. Sci. U.S.A., 51, p. 786 Roth, S.Y., Denu, J.M., Allis, C.D., (2001) Annu. Rev. Biochem., 70, p. 81 Yang, X.-J., Seto, E., (2008) Mol. Cell, 31, p. 449 Liu, Y., Colosimo, A.L., Yang, X.-J., Liao, D., (2000) Mol. Cell. Biol., 20, p. 5540 Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Yao, T.-P., (2002) Nature, 417, p. 455 Glozak, M.A., Sengupta, N., Zhang, X., Seto, E., (2005) Gene, 363, p. 15 Matthias, P., Yoshida, M., Khochbin, S., (2008) Cell Cycle, 7, p. 7 Arif, M., Selvi, B.R., Kundu, T.K., (2010) ChemBioChem, 11, p. 1501 Von Wantoch Rekowski, M., Giannis, A., (2010) Biochim. Biophys. Acta, Gene Regul. Mech., 1799, p. 760 Zhao, S., Xu, W., Jiang, W., Yu, W., Lin, Y., Zhang, T., Yao, J., Guan, K.-L., (2010) Science, 327, p. 1000 Wang, Q., Zhang, Y., Yang, C., Xiong, H., Lin, Y., Yao, J., Li, H., Zhao, G.-P., (2010) Science, 327, p. 1004 Allis, C.D., Berger, S.L., Cote, J., Dent, S., Jenuwien, T., Kouzarides, T., Pillus, L., Zhang, Y., (2007) Cell, 131, p. 633 Lysine acetylation was initially identified in histones, so many KATs and KDACs are often referred to as histone acetyltransferases (HATs) and deacetylases (HDACs), respectivelyDekker, F.J., Haisma, H.J., (2009) Drug Discovery Today, 14, p. 942 Manzo, F., Tambaro, F.P., Mai, A., Altucci, L., (2009) Expert Opin. Ther. Pat., 19, p. 761 Howe, L., Auston, D., Grant, P., John, S., Cook, R.G., Workman, J.L., Pillus, L., (2001) Genes Dev., 15, p. 3144 Gayther, S.A., Batley, S.J., Linger, L., Bannister, A., Thorpe, K., Chin, S.-F., Daigo, Y., Caldas, C., (2000) Nat. Genet., 24, p. 300 Bandyopadhyay, D., Okan, N.A., Bales, E., Nascimento, L., Cole, P.A., Medrano, E.E., (2002) Cancer Res., 62, p. 6231 Giordano, A., Avantaggiati, M.L., (1999) J. Cell. Physiol., 181, p. 218 Pfister, S., Rea, S., Taipale, M., Mendrzyk, F., Straub, B., Ittrich, C., Thuerigen, O., Lichter, P., (2008) Int. J. Cancer, 122, p. 1207 Katsumoto, T., Yoshida, N., Kitabayashi, I., (2008) Cancer Sci., 99, p. 1523 Iyer, N.G., Xian, J., Chin, S.F., Bannister, A.J., Daigo, Y., Aparicio, S., Kouzarides, T., Caldas, C., (2007) Oncogene, 26, p. 21 Kitabayashi, I., Aikawa, Y., Yokoyama, A., Hosoda, F., Nagai, M., Kakazu, N., Abe, T., Ohki, M., (2001) Leukemia, 15, p. 89 Ait-Si-Ali, S., Polesskaya, A., Filleur, S., Ferreira, R., Duquet, A., Robin, P., Vervish, A., Harel-Bellan, A., (2000) Oncogene, 19, p. 2430 Adcock, I.M., Tsaprouni, L., Bhavsar, P., Ito, K., (2007) Curr. Opin. Immunol., 19, p. 694 Yang, X.J., (2004) Nucleic Acids Res., 32, p. 959 Mantelingu, K., Reddy, B.A.A., Swaminathan, V., Kishore, A.H., Siddappa, N.B., Kumar, G.V.P., Nagashankar, G., Kundu, T.K., (2007) Chem. Biol., 14, p. 645 Barnes, P.J., Adcock, I.M., Ito, K., (2005) Eur. Resp. J., 25, p. 552 Lau, O.D., Kundu, T.K., Soccio, R.E., Ait-Si-Ali, S., Khalil, E.M., Vassilev, A., Wolffe, A.P., Cole, P.A., (2000) Mol. Cell, 5, p. 589 Saha, R.N., Pahan, K., (2005) Cell Death Differ., 13, p. 539 Rouaux, C., Jokic, N., Mbebi, C., Boutillier, S., Loeffler, J.-P., Boutillier, A.-L., (2003) EMBO J., 22, p. 6537 Barrett, R.M., Wood, M.A., (2008) Learn. Memory, 15, p. 460 Maurice, T., Duclot, F., Meunier, J., Naert, G., Givalois, L., Meffre, J., Celerier, A., Gongora, C., (2007) Neuropsychopharmacology, 33, p. 1584 Mai, A., Massa, S., Rotili, D., Cerbara, I., Valente, S., Pezzi, R., Simeoni, S., Ragno, R., (2005) Med. Res. Rev., 25, p. 261 Minucci, S., Pelicci, P.G., (2006) Nat. Rev. Cancer, 6, p. 38 Richon, V.M., Emiliani, S., Verdin, E., Webb, Y., Breslow, R., Rifkind, R.A., Marks, P.A., (1998) Proc. Natl. Acad. Sci. U.S.A., 95, p. 3003 Nakajima, H., Kim, Y.B., Terano, H., Yoshida, M., Horinouchi, S., (1998) Exp. Cell. Res., 241, p. 126 Nagy, Z., Tora, L., (2007) Oncogene, 26, p. 5341 Marmorstein, R., Trievel, R.C., (2009) Biochim. Biophys. Acta, Gene Regul. Mech., 1789, p. 58 Lee, K.K., Workman, J.L., (2007) Nat. Rev. Mol. Cell Biol., 8, p. 284 Hodawadekar, S.C., Marmorstein, R., (2007) Oncogene, 26, p. 5528 Brownell, J.E., Zhou, J., Ranalli, T., Kobayashi, R., Edmondson, D.G., Roth, S.Y., Allis, C.D., (1996) Cell, 84, p. 843 Stockwell, B.R., (2000) Nat. Rev. Genet., 1, p. 116 Bowers, E.M., Yan, G., Mukherjee, C., Orry, A., Wang, L., Holbert, M.A., Crump, N.T., Cole, P.A., (2010) Chem. Biol., 17, p. 471 Cebrat, M., Kim, C.M., Thompson, P.R., Daugherty, M., Cole, P.A., (2003) Bioorg. Med. Chem., 11, p. 3307 Balasubramanyam, K., Swaminathan, V., Ranganathan, A., Kundu, T.K., (2003) J. Biol. Chem., 278, p. 19134 Ravindra, K.C., Selvi, B.R., Arif, M., Reddy, B.A.A., Thanuja, G.R., Agrawal, S., Pradhan, S.K., Kundu, T.K., (2009) J. Biol. Chem., 284, p. 24453 Dal Piaz, F., Tosco, A., Eletto, D., Piccinelli, A.L., Moltedo, O., Franceschelli, S., Sbardella, G., De Tommasi, N., (2010) ChemBioChem, 11, p. 818 Eliseeva, E.D., Valkov, V., Jung, M., Jung, M.O., (2007) Mol. Cancer Ther., 6, p. 2391 Ghizzoni, M., Boltjes, A., Graaf, C.D., Haisma, H.J., Dekker, F.J., (2010) Bioorg. Med. Chem., 18, p. 5826 Souto, J.A., Conte, M., Álvarez, R., Nebbioso, A., Carafa, V., Altucci, L., De Lera, A.R., (2008) ChemMedChem, 3, p. 1435 Costi, R., Di Santo, R., Artico, M., Miele, G., Valentini, P., Novellino, E., Cereseto, A., (2007) J. Med. Chem., 50, p. 1973 Mai, A., Cheng, D., Bedford, M.T., Valente, S., Nebbioso, A., Perrone, A., Brosch, G., Altucci, L., (2008) J. Med. Chem., 51, p. 2279 Dekker, F.J., Ghizzoni, M., Van Der Meer, N., Wisastra, R., Haisma, H.J., (2009) Bioorg. Med. Chem., 17, p. 460 Ghizzoni, M., Haisma, H.J., Dekker, F.J., (2009) Eur. J. Med. Chem., 44, p. 4855 Gorsuch, S., Bavetsias, V., Rowlands, M.G., Aherne, G.W., Workman, P., Jarman, M., McDonald, E., (2009) Bioorg. Med. Chem., 17, p. 467 Stimson, L., Rowlands, M.G., Newbatt, Y.M., Smith, N.F., Raynaud, F.I., Rogers, P., Bavetsias, V., Aherne, G.W., (2005) Mol. Cancer Ther., 4, p. 1521 Biel, M., Kretsovali, A., Karatzali, E., Papamatheakis, J., Giannis, A., (2004) Angew. Chem., Int. Ed., 43, p. 3974 Mai, A., Rotili, D., Tarantino, D., Ornaghi, P., Tosi, F., Vicidomini, C., Sbardella, G., Filetici, P., (2006) J. Med. Chem., 49, p. 6897 Sbardella, G., Castellano, S., Vicidomini, C., Rotili, D., Nebbioso, A., Miceli, M., Altucci, L., Mai, A., (2008) Bioorg. Med. Chem. Lett., 18, p. 2788 Dess, D.B., Martin, J.C., (1991) J. Am. Chem. Soc., 113, p. 7277 Haldar, J., Kondaiah, P., Bhattacharya, S., (2005) J. Med. Chem., 48, p. 3823 Ahlquist, L., Asselineau, C., Asselineau, J., Stallberg-Stenhagen, S., Stenhagen, E., (1958) Ark. Kemi, 31, p. 543 Comeau, D., Lai, R., Charlot, C., Ucciani, E., (1972) Bull. Soc. Chim. Fr., p. 4163 Actually, as noticeable in Figure 5B, a slight acetylation was observed for both compounds at 15 μM concentration. Yet, it was completely undetectable at 30 μMVarier, R.A., Swaminathan, V., Balasubramanyam, K., Kundu, T.K., (2004) Biochem. Pharmacol., 68, p. 1215 In these conditions, compound 2b caused excessive cell deathTurner, B.M., (2005) Nat. Struct. Mol. Biol., 12, p. 110 Mai, A., Esposito, M., Sbardella, G., Massa, S., (2001) Org. Prep. Proced. Int., 33, p. 391 Chang, Y.-H., Uang, B.-J., Wu, C.-M., Yu, T.-H., (1990) Synthesis, 1990, p. 1033 Sorg, G., Mengel, A., Jung, G., Rademann, J., (2001) Angew. Chem., Int. Ed., 40, p. 4395 Kraus, W.L., Kadonaga, J.T., (1998) Genes Dev., 12, p. 331 Nebbioso, A., Clarke, N., Voltz, E., Germain, E., Ambrosino, C., Bontempo, P., Alvarez, R., Altucci, L., (2005) Nat. Med., 11, p. 77 Cooper, M., (2003) Anal. Bioanal. Chem., 377, p. 834 Johnsson, B., Löfs, S., Lindquist, G., (1991) Anal. Biochem., 198, p. 268}, document_type={Journal Article, }, affiliation={Dipartimento di Scienze Farmaceutiche, Università Degli Studi di Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy Dipartimento di Patologia Generale, Seconda Università Degli Studi di Napoli, Vico L. De Crecchio 7, 80138 Napoli, Italy Dipartimento di Fisica, Università di Napoli Federico II, Napoli, Italy IGB-CNR, Via Pietro Castellino, 80100, Napoli, Italy Dipartimento di Chimica e Tecnologie Del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza Università di Roma, P.le A. Moro 5, 00185 Roma, Italy}, ibbaffiliation={1}, } @article{IBB_ID_52152, author={Pellecchia MT, Barone P, Vicidomini C, Mollica C, Salvatore E, Ianniciello M, Liuzzi R, Longo K, Picillo M, De Michele G, Filla A, Brunetti A, Salvatore M, Pappata S}, title={Progression of striatal and extrastriatal degeneration in multiple system atrophy: a longitudinal diffusion-weighted MR study}, date={2011 Jun}, journal={Mov Disord (ISSN: 1531-8257, 0885-3185, 0885-3185linking)}, year={2011}, fullvolume={355}, volume={355}, pages={1303--1309}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79959351063&partnerID=40&md5=4472c87e6c9941c25130e040008fdd51}, abstract={Diffusion-weighted imaging has been largely used to detect and quantify early degenerative changes in patients with multiple system atrophy, but progression of neurodegeneration has been poorly investigated. We performed a serial diffusion-weighted imaging study in a population of multiple system atrophy patients and analyzed the evolution of diffusion properties in striatal and extrastriatal brain regions. Diffusion-weighted imaging was obtained in 11 multiple system atrophy patients at baseline and after a follow-up of 11.7 ± 1.2 months, and Trace (D) changes in different brain regions were correlated with disease duration and severity. A significant increase in Trace (D) was observed at follow-up in the putamen (P < .001), pons (P = .003), cerebellar white matter (P = .03), thalamus (P = .013), and frontal white matter (P = .021). Both Unified Multiple System Atrophy Rating Scale Part II and Unified Parkinson's Disease Rating Scale Part III scores significantly increased at follow-up (P = .003), but percent changes of Unified Parkinson's Disease Rating Scale Part III and Unified Multiple System Atrophy Rating Scale Part II did not correlate with percent changes of Trace (D) values in any brain region. This longitudinal study provides new insights into the progression of neurodegeneration in different brain regions in multiple system atrophy. Our results confirm that abnormal diffusivity in the putamen is sensitive to change over time in multiple system atrophy patients and show for the first time a progression of Trace (D) alterations in specific extrastriatal regions. Diffusivity changes in these regions may be useful for monitoring disease progression even after a short follow-up period. 2011 Movement Disorder Society. Copyright 2011 Movement Disorder Society.}, keywords={Diffusion-Weighted Imaging, Longitudinal Study, Multiple System Atrophy, Adult, Article, Clinical Article, Clinical Feature, Corpus Striatum, Correlation Analysis, Diffusion Weighted Imaging, Disease Course, Disease Duration, Disease Severity, Female, Follow Up, Frontal Lobe, Human, Named Inventories, Questionnaires And Rating Scales, Nerve Degeneration, Pons, Priority Journal, Putamen, Scoring System, Shy Drager Syndrome, Thalamus, Unified Multiple System Atrophy Rating Scale, Unified Parkinson Disease Rating Scale, White Matter, Diffusion Magnetic Resonance Imaging, Disease Progression, Follow-Up Studies, Longitudinal Studies, Middle Aged, }, references={Wenning, G.K., Ben-Shlomo, Y., Magalhaes, M., Daniel, S.E., Quinn, N.P., Clinical features and natural history of multiple system atrophy: an analysis of 100 cases (1994) Brain, 117, pp. 835-84 Kume, A., Takahashi, A., Hashizume, Y., Neuronal cell loss of the striatonigral system in multiple system atrophy (1993) J Neurol Sci, 117, pp. 33-40 Wenning, G.K., Tison, F., Ben Shlomo, Y., Daniel, S.E., Quinn, N.P., Multiple system atrophy: a review of 203 pathologically proven cases (1997) Mov Disord, 12, pp. 133-147 Gilman, S., Wenning, G.K., Low, P.A., Second consensus statement on the diagnosis of multiple system atrophy (2008) Neurology, 71, pp. 670-676 Schocke, M.F.H., Seppi, K., Esterhammer, R., Diffusion-weighted MRI differentiates the Parkinson variant of multiple system atrophy from PD (2002) Neurology, 58, pp. 575-580 Seppi, K., Schocke, M.F.H., Esterhammer, R., Diffusion-weighted imaging discriminates progressive supranuclear palsy from PD, but not from the parkinson variant of multiple system atrophy (2003) Neurology, 60, pp. 922-927 Nicoletti, G., Lodi, R., Condino, F., Apparent diffusion coefficient measurements of the middle cerebellar peduncle differenziate the Parkinson variant of MSA from Parkinson's disease and progressive supranuclear palsy (2006) Brain, 129, pp. 2679-2687 Paviour, D.C., Thornton, J.S., Lees, A.J., Jager, H.R., Diffusion-weighted magnetic resonance imaging differentiates parkinsonian variant of multiple system atrophy from progressive supranuclear palsy (2007) Mov Disord, 22, pp. 60-74 Hajnal, J.V., Doran, M., Hall, A.S., MR imaging of anisotropically restricted diffusion of water in the nervous system: technical, anatomic, and pathologic considerations (1991) J Comput Assist Tomogr, 15, pp. 1-18 Le Bihan, D., Turner, R., Douek, P., Patronas, N., Diffusion MR imaging: clinical applications (1992) Am J Roentgenol, 159, pp. 359-362 Pellecchia, M.T., Barone, P., Mollica, C., Diffusion-weighted imaging in multiple system atrophy: A comparison between clinical subtypes (2009) Mov Disord, 24, pp. 689-696 Brenneis, C., Egger, K., Scherfler, C., Progression of brain atrophy in multiple system atrophy. A longitudinal VBM study (2007) J Neurol, 254, pp. 191-196 Kanazawa, M., Shimohata, T., Terajima, K., Quantitative evaluation of brainstem involvement in multiple system atrophy by diffusion-weighted MR imaging (2004) J Neurol, 251, pp. 1121-1124 Minnerop, M., Specht, K., Ruhlmann, J., Voxel-based morphometry and voxel-based relaxometry in multiple system atrophy-a comparison between clinical subtypes and correlations with clinical parameters (2007) Neuroimage, 15 (36), pp. 1086-1095 Tzarouchi, L.C., Astrakas, L.G., Kontsiotis, S., Voxel-based morphometry and voxel-based relaxometry in parkinsonian variant of multiple system atrophy (2010) J Neuroimaging, 20, pp. 260-266 Chang, C.C., Chang, Y.Y., Chang, W.N., Cognitive deficits in multiple system atrophy correlate with frontal atrophy and disease duration (2009) Eur J Neurol, 16, pp. 1144-1150 Kitayama, M., Wada-Isoe, K., Irizawa, Y., Nakashima, K., Assessment of dementia in patients with multiple system atrophy (2009) Eur J Neurol, 16, pp. 589-594 Armstrong, R.A., Cairns, N.J., Lantos, P.L., A quantitative study of the pathological changes in white matter in multiple system atrophy (2007) Neuropathology, 27, pp. 221-227 Lyoo, C.H., Yeong, Y., Ryu, Y.H., Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy (2008) Brain, 131, pp. 438-446 Naganawa, S., Sato, K., Katagiri, T., Mimura, T., Ishigaki, T., Regional ADC values of the normal brain: differences due to age, gender, and laterality (2003) Eur Radiol, 13, pp. 6-11 Abe, O., Aoki, S., Ayashi, N., Normal aging in the central nervous system: quantitative MR diffusion-tensor analysis (2002) Neurobiol Aging, 23, pp. 433-441 Engelter, S.T., Provenzale, J.M., Petrella, J.R., DeLong, D.M., MacFall, J.R., The effect of aging on the apparent diffusion coefficient of normal-appearing white matter (2000) Am J Roentgenol, 175, pp. 425-430 Molko, N., Pappata, S., Mangin, J.F., Monitoring disease progression in CADASIL with diffusion magnetic resonance imaging: a study with whole brain histogram analysis (2002) Stroke, 33, pp. 2902-2908 Vandenberghe, W., Demaerel, P., Dom, R., Maes, F., Diffusion-weighted versus volumetric imaging of the striatum in early symptomatic Huntington disease (2009) J Neurol, 256, pp. 109-114 Fox, N.C., Cousens, S., Scahill, R., Harvey, R.J., Rossor, M.N., Using serial registered brain magnetic resonance imaging to measure disease progression in Alzheimer disease: power calculations and estimates of sample size to detect treatment effects (2000) Arch Neurol, 57, pp. 339-344 Paviour, D.C., Price, S.L., Lees, A.J., Fox, N.C., MRI derived brain atrophy in PSP and MSA-P. Determining sample size to detect treatment effects (2007) J Neurol, 254, pp. 478-481}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Department of Neurological Sciences, University Federico II, Naples, Italy. Institute of Diagnosis and Care Hermitage Capodimonte, Naples, Italy Institute of Biostructure and Bioimaging, CNR, Naples, Italy IRCCS Fondazione SDN, Naples, Italy Department of Biomorphological Sciences, University Federico II, Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_8943, author={Pappata S, Varrone A, Vicidomini C, Milan G, De Falco C, Sansone V, Iavarone A, Comerci M, Loré E, Panico M, Quarantelli M, Postiglione A, Salvatore M}, title={SPECT imaging of GABAA/benzodiazepine receptors and cerebral perfusion in mild cognitive impairment}, date={2010 Jun}, journal={Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997)}, year={2010}, fullvolume={481}, volume={481}, pages={1156--1163}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77954888295&partnerID=40&md5=76556b0525c1b07d6be1e3bd80c00124}, abstract={PURPOSE: The involvement of neocortical and limbic GABA(A)/benzodiazepine (BZD) receptors in Alzheimer's disease (AD) is controversial and mainly reported in advanced stages. The status of these receptors in the very early stages of AD is unclear and has not been explored in vivo. Our aims were to investigate in vivo the integrity of cerebral cortical GABA(A)/BZD receptors in subjects with amnestic mild cognitive impairment (MCI) and to compare possible receptor changes to those in cerebral perfusion. METHODS: [(123)I]Iomazenil and [(99m)Tc]HMPAO SPECT images were acquired in 16 patients with amnestic MCI and in 14 normal elderly control subjects (only [(123)I]iomazenil imaging in 5, only [(99m)Tc]HMPAO imaging in 4, and both [(123)I]iomazenil and [(99m)Tc]HMPAO imaging in 5). Region of interest (ROI) analysis and voxel-based analysis were performed with cerebellar normalization. RESULTS: Neither ROI analysis nor voxel-based analysis showed significant [(123)I]iomazenil binding changes in MCI patients compared to control subjects, either as a whole group or when considering only those patients with MCI that converted to AD within 2 years of clinical follow-up. In contrast, the ROI analysis revealed significant hypoperfusion of the precuneus and posterior cingulate cortex in the whole group of MCI patients and in MCI converters as compared to control subjects. Voxel-based analysis showed similar results. CONCLUSION: These results indicate that in the very early stages of AD, neocortical and limbic neurons/synapses expressing GABA(A)/BZD receptors are essentially preserved. They suggest that in MCI patients functional changes precede neuronal/synaptic loss in neocortical posterior regions and that [(99m)Tc]HMPAO rCBF imaging is more sensitive than [(123)I]iomazenil GABA(A)/BZD receptor imaging in detecting prodromal AD.}, keywords={Alzheimer, Benzodiazepine Receptors, Cerebral Perfusion, Iomazenil, Mild Cognitive Impairment, Spect, 4 Aminobutyrate Aminotransferase, Hexamethylpropylene Amine Oxime Technetium Tc 99m, Iomazenil I 123, Radiopharmaceutical Agent, Unclassified Drug, Alzheimer Disease, Amnesia, Article, Brain Blood Flow, Brain Cortex, Brain Perfusion, Cell Loss, Cingulate Gyrus, Clinical Article, Controlled Study, Episodic Memory, Female, Follow Up, Human, In Vivo Study, Limbic Cortex, Neocortex, Nerve Cell, Receptor Binding, Single Photon Emission Computer Tomography, Synapse, Voxel Based Morphometry, Case-Control Studies, Cerebrovascular Circulation, Cognition Disorders, Flumazenil, Middle Aged, Gaba-A, Emission-Computed, Single-Photon, Alzheimer Disease Metabolism Pathology Physiopathology Radionuclide Imaging, Cognition Disorders Metabolism Pathology Physiopathology Radionuclide Imaging, Flumazenil Analogs, Derivatives Metabolism, Gaba-A Metabolism, Synapses Metabolism, Alzheimer Disease Diagnostic Imaging Metabolism Pathology Physiopathology , Cognition Disorders Diagnostic Imaging Metabolism Pathology Physiopathology, }, references={Pappatà, S., Salvatore, E., Postiglione, A., In vivo imaging of neurotransmission and brain receptors in dementia (2008) J. Neuroimaging, 18, pp. 111-2 Rissman, R.A., De Blas, A.L., Armstrong, D.M., GABA (A) receptors in aging and Alzheimer's disease (2007) J. Neurochem., 103, pp. 1285-92 Möhler, H., Molecular regulation of cognitive functions and developmental plasticity: Impact of GABAA receptors (2007) J. Neurochem., 102, pp. 1-12 Lanctot, K.L., Herrmann, N., Mazzotta, P., Khan, L.R., Ingber, N., GABAergic function in Alzheimer's disease: Evidence for dysfunction and potential as a therapeutic target for the treatment of behavioral and psychological symptoms of dementia (2004) Can J. Psychiatry, 49, pp. 439-53 Louzada, P.R., Lima, A.C.P., Mendonca-Silva, D.L., Noël, F., De Mello, F.G., Ferreira, S.T., Taurine prevents the neurotoxicity of betaamyloid and glutamate receptor agonists: Activation of GABA receptors and possible implications for Alzheimer's disease and other neurological disorders (2004) FASEB J., 18, pp. 511-8 Rissman, R.A., Bennett, D.A., Armstrong, D.M., Subregional analysis of GABA (A) receptor subunit mRNAs in the hippocampus of older persons with and without cognitive impairment (2004) J. Chem. Neuroanat, 28, pp. 17-25 Soricelli, A., Postiglione, A., Grivet-Fojaja, M.R., Mainenti, P.P., Discepolo, A., Varrone, A., Reduced cortical distribution volume of iodine-123 iomazenil in Alzheimer's disease as a measure of loss of synapses (1996) Eur. J. Nucl Med., 23, pp. 1323-8 Fukuchi, K., Hashikawa, K., Seike, Y., Moriwaki, H., Oku, N., Ishida, M., Comparison of iodine-123-iomazenil SPECT and technetium-99m-HMPAO-SPECT in Alzheimer's disease (1997) J. Nucl Med., 38, pp. 467-70 Meyer, M., Koeppe, R.A., Frey, K.A., Foster, N.L., Kuhl, D.E., Positron emission tomography measures of benzodiazepine binding in Alzheimer's disease (1995) Arch. Neurol., 52, pp. 314-7 Ohyama, M., Senda, M., Ishiwata, K., Kitamura, S., Mishina, M., Ishii, K., Preserved benzodiazepine receptors in Alzheimer's disease measured with C-11 flumazenil PET and I-123 iomazenil SPECT in comparison with CBF (1999) Ann. Nucl Med., 13, pp. 309-15 Petersen, R.C., Smith, G.E., Waring, S.C., Ivnik, R.J., Tangalos, E.G., Kokmen, E., Mild cognitive impairment: Clinical characterization and outcome (1999) Arch. Neurol., 56, pp. 303-8 Millet, P., Graf, C., Buck, A., Walder, B., Westera, G., Broggini, C., Similarity and robustness of PET and SPECT binding parameters for benzodiazepine receptors (2000) J. Cereb. Blood Flow Metab., 20, pp. 1587-603 Greenamyre, J.T., Penney, J.B., D'Amato, C.J., Young, A.B., Dementia of the Alzheimer's type: Changes in hippocampal L-[3H]glutamate binding (1987) J. Neurochem., 48, pp. 543-51 Jansen, K.L., Faull, R.L., Dragunow, M., Synek, B.L., Alzheimer's disease: Changes in hippocampal N-methyl-D-aspartate, quisqualate, neurotensin, adenosine, benzodiazepine, serotonin and opioid receptors - An autoradiographic study (1990) Neuroscience, 39, pp. 613-27 Shimohama, S., Taniguchi, T., Fujiwara, M., Kameyama, M., Changes in benzodiazepine receptors in Alzheimer-type dementia (1988) Ann. Neurol., 23, pp. 404-6 Cross, A.J., Crow, T.J., Ferrier, I.N., Johnson, J.A., The selectivity of the reduction of serotonin S2 receptors in Alzheimer-type dementia (1986) Neurobiol. Aging, 7, pp. 3-7 Owen, F., Poulter, M., Waddington, J.L., Mashal, R.D., Crow, T.J., [3H]R05-4864 and [3H]flunitrazepam binding in kainatelesioned rat striatum and in temporal cortex of brains from patients with senile dementia of the Alzheimer type (1983) Brain Res., 278, pp. 373-5 Chu, D.C., Penney Jr., J.B., Young, A.B., Cortical GABAB and GABAA receptors in Alzheimer's disease: A quantitative autoradiographic study (1987) Neurology, 37, pp. 1454-9 Lloyd, G.K., Lowenthal, A., Javoy-Agid, F., Constantidinis, J., GABAA receptor complex function in frontal cortex membranes from control and neurological patients (1991) Eur. J. Pharmacol., 197, pp. 33-9 Vogt, B.A., Crino, P.B., Volicer, L., Laminar alterations in gammaaminobutyric acidA, muscarinic, and beta adrenoceptors and neuron degeneration in cingulate cortex in Alzheimer's disease (1991) J. Neurochem., 57, pp. 282-90 Howell, O., Atack, J.R., Dewar, D., McKernan, R.M., Sur, C., Density and pharmacology of alpha5 subunit-containing GABA (A) receptors are preserved in hippocampus of Alzheimer's disease patients (2000) Neuroscience, 98, pp. 669-75 Mizukami, K., Ikonomovic, M.D., Grayson, D.R., Immunohistochemical study of GABAA receptor alpha1 subunit in the hippocampal formation of aged brains with Alzheimer-related neuropathologic changes (1998) Brain Res., 799, pp. 148-55 Penney, J.B., Maragos, W.F., Greenamyre, J.T., Debowey, D.L., Hollingsworth, Z., Young, A.B., Excitatory amino acid binding sites in the hippocampal region of Alzheimer's disease and other dementias (1990) J. Neurol. Neurosurg. Psychiatry, 53, pp. 314-20 Hof, P.R., Cox, K., Young, W.G., Celio, M.R., Rogers, J., Morrison, J.H., Parvalbumin-immunoreactive neurons in the neocortex are resistant to degeneration in Alzheimer's disease (1991) J. Neuropathol Exp. Neurol., 50, pp. 451-62 Price, J.L., Ko, A.I., Wade, M.J., Tsou, S.K., McKeel, D.W., Morris, J.C., Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease (2001) Arch. Neurol., 58, pp. 1395-402 Bell, K.F., Cuello, A.C., Altered synaptic function in Alzheimer's disease (2006) Eur. J. Pharmacol., 545, pp. 11-21 Palop, J.J., Chin, J., Roberson, E.D., Wang, J., Thwin, M.T., Bien-Ly, N., Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease (2007) Neuron, 55, pp. 697-711 DeKosky, S.T., Ikonomovic, M.D., Styren, S.D., Beckett, L., Wisniewski, S., Bennett, D.A., Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment (2002) Ann. Neurol., 51, pp. 145-55 Truchot, L., Costes, S.N., Zimmer, L., Laurent, B., Le Bars, D., Thomas-Antérion, C., Up-regulation of hippocampal serotonin metabolism in mild cognitive impairment (2007) Neurology, 69, pp. 1012-7 Borroni, B., Anchisi, D., Paghera, B., Combined 99mTc-ECD SPECT and neuropsychological studies in MCI for the assessment of conversion to AD (2006) Neurobiol. Aging, 27, pp. 24-31 Chetelat, G., Desgranges, B., De La Sayette, V., Viader, F., Berkouk, K., Landeau, B., Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment (2003) Brain, 126, pp. 1955-67 Pappat, S., Salvatore, E., Postiglione, A., In vivo imaging of neurotransmission and brain receptors in dementia (2008) J. Neuroimaging, 18, pp. 111-2 Rissman, R. A., De Blas, A. L., Armstrong, D. M., GABA (A) receptors in aging and Alzheimer's disease (2007) J. Neurochem., 103, pp. 1285-92 M hler, H., Molecular regulation of cognitive functions and developmental plasticity: Impact of GABAA receptors (2007) J. Neurochem., 102, pp. 1-12 Lanctot, K. L., Herrmann, N., Mazzotta, P., Khan, L. R., Ingber, N., GABAergic function in Alzheimer's disease: Evidence for dysfunction and potential as a therapeutic target for the treatment of behavioral and psychological symptoms of dementia (2004) Can J. Psychiatry, 49, pp. 439-53 Louzada, P. R., Lima, A. C. P., Mendonca-Silva, D. L., No l, F., De Mello, F. G., Ferreira, S. T., Taurine prevents the neurotoxicity of betaamyloid and glutamate receptor agonists: Activation of GABA receptors and possible implications for Alzheimer's disease and other neurological disorders (2004) FASEB J., 18, pp. 511-8 Rissman, R. A., Bennett, D. A., Armstrong, D. M., Subregional analysis of GABA (A) receptor subunit mRNAs in the hippocampus of older persons with and without cognitive impairment (2004) J. Chem. Neuroanat, 28, pp. 17-25 Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., Kokmen, E., Mild cognitive impairment: Clinical characterization and outcome (1999) Arch. Neurol., 56, pp. 303-8 Greenamyre, J. T., Penney, J. B., D'Amato, C. J., Young, A. B., Dementia of the Alzheimer's type: Changes in hippocampal L- [3H] glutamate binding (1987) J. Neurochem., 48, pp. 543-51 Jansen, K. L., Faull, R. L., Dragunow, M., Synek, B. L., Alzheimer's disease: Changes in hippocampal N-methyl-D-aspartate, quisqualate, neurotensin, adenosine, benzodiazepine, serotonin and opioid receptors - An autoradiographic study (1990) Neuroscience, 39, pp. 613-27 Cross, A. J., Crow, T. J., Ferrier, I. N., Johnson, J. A., The selectivity of the reduction of serotonin S2 receptors in Alzheimer-type dementia (1986) Neurobiol. Aging, 7, pp. 3-7 Chu, D. C., Penney Jr., J. B., Young, A. B., Cortical GABAB and GABAA receptors in Alzheimer's disease: A quantitative autoradiographic study (1987) Neurology, 37, pp. 1454-9 Lloyd, G. K., Lowenthal, A., Javoy-Agid, F., Constantidinis, J., GABAA receptor complex function in frontal cortex membranes from control and neurological patients (1991) Eur. J. Pharmacol., 197, pp. 33-9 Vogt, B. A., Crino, P. B., Volicer, L., Laminar alterations in gammaaminobutyric acidA, muscarinic, and beta adrenoceptors and neuron degeneration in cingulate cortex in Alzheimer's disease (1991) J. Neurochem., 57, pp. 282-90 Penney, J. B., Maragos, W. F., Greenamyre, J. T., Debowey, D. L., Hollingsworth, Z., Young, A. B., Excitatory amino acid binding sites in the hippocampal region of Alzheimer's disease and other dementias (1990) J. Neurol. Neurosurg. Psychiatry, 53, pp. 314-20 Hof, P. R., Cox, K., Young, W. G., Celio, M. R., Rogers, J., Morrison, J. H., Parvalbumin-immunoreactive neurons in the neocortex are resistant to degeneration in Alzheimer's disease (1991) J. Neuropathol Exp. Neurol., 50, pp. 451-62 Price, J. L., Ko, A. I., Wade, M. J., Tsou, S. K., McKeel, D. W., Morris, J. C., Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease (2001) Arch. Neurol., 58, pp. 1395-402 Bell, K. F., Cuello, A. C., Altered synaptic function in Alzheimer's disease (2006) Eur. J. Pharmacol., 545, pp. 11-21 Palop, J. J., Chin, J., Roberson, E. D., Wang, J., Thwin, M. T., Bien-Ly, N., Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease (2007) Neuron, 55, pp. 697-711 DeKosky, S. T., Ikonomovic, M. D., Styren, S. D., Beckett, L., Wisniewski, S., Bennett, D. A., Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment (2002) Ann. Neurol., 51, pp. 145-55}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Institute of Biostructure and Bioimaging, CNR, Via Pansini 5, 80131 Naples, Italy Department of Clinical and Experimental Medicine, University Federico II, Naples, Italy Department of Biomorphological and Functional Sciences, University Federico II, Naples, Italy Neurologic and Stroke Unit, CTO Hospital, Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_52157, author={Bilo L, Meo R, de Leva MF, Vicidomini C, Salvatore M, Pappata S}, title={Thalamic activation and cortical deactivation during typical absence status monitored using [18F]FDG-PET: a case report}, date={2010 Apr}, journal={Seizure (ISSN: 1532-2688, 1059-1311)}, year={2010}, fullvolume={463}, volume={463}, pages={198--201}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77549088326&partnerID=40&md5=9103c5f33f954a983d442d80bbdcf8b3}, abstract={We describe the ictal [(18)F]FDG-PET study of a case of absence status showing bilateral thalamic hypermetabolism and frontal cortex hypometabolism. This is the first ictal assessment of absence status by [(18)F]FDG-PET reporting this particular cortical and subcortical involvement. Our findings support the theory of corticothalamic circuitry involvement in the pathophysiology of absence seizures and stress the similarities of the clinical and metabolic pattern observed during absences with the pattern of task-induced interruption of the default state of brain function. (c) 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.}, keywords={Absence Status Epilepticus, Default State, Fdg-Pet Study, Fluorodeoxyglucose F 18, Adult, Article, Brain Metabolism, Case Report, Frontal Cortex, Glucose Metabolism, Human, Nuclear Magnetic Resonance Imaging, Priority Journal, Stress, Thalamus, Tonic Clonic Seizure, Cerebral Cortex, Image Interpretation, Computer-Assisted, Middle Aged, Positron-Emission Tomography, Radiopharmaceuticals, }, references={Aghakhani, Y., Bagshaw, A.P., Bénar, C.G., Hawco, C., Andermann, F., Dubeau, F., fMRI activation during spike and wave discharges in idiopathic generalized epilepsy (2004) Brain, 127, pp. 1127-114 Blumenfeld, H., From molecules to networks: cortical/subcortical interactions in the pathophysiology of idiopathic generalized epilepsy (2003) Epilepsia, 44, pp. 7-15 Duncan, J.S., Brain imaging in idiopathic generalized epilepsies (2005) Epilepsia, 46, pp. 108-111 Engel Jr., J., Lubens, P., Kuhl, D.E., Phelps, M.E., Local cerebral metabolic rate for glucose during petit mal absences (1985) Ann Neurol, 17, pp. 121-128 Gotman, J., Grova, C., Bagshaw, A., Kobayashi, E., Aghakani, Y., Dubeau, F., Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain (2005) Proc Natl Acad Sci USA, 102, pp. 15236-15240 Panayiotopoulos, C.P., (2005) Absence Status Epilepticus, , http://www.ilae-epilepsy/Visitors/Centre/ctf/absence_status.cfm, http://www.ilae-epilepsy/Visitors/Centre/ctf/absence_status.cfm Prevett, M.C., Duncan, J.S., Jones, T., Fish, D.R., Brooks, D.J., Demonstration of thalamic activation during typical absence seizures using H 2(15)O and PET (1995) Neurology, 45, pp. 1396-1402 Raichle, M.E., MacLeod, A.M., Snyder, A.Z., Powers, W.J., Gusnard, D.A., Shulman, G.L., A default mode of brain function (2001) Proc Natl Acad Sci USA, 98, pp. 676-682 Salek-Haddadi, A., Lemieux, L., Merschhemke, M., Friston, K.J., Duncan, J.S., Fish, D.R., Functional magnetic resonance imaging of human absence seizures (2003) Ann Neurol, 53, pp. 663-667 Shorvon, S., Walker, M., Status epilepticus in idiopathic generalized epilepsy (2005) Epilepsia, 46, pp. 73-79 Theodore, W.H., Brooks, R., Margolin, R., Patronas, N., Sato, S., Porter, R.J., Positron emission tomography in generalized seizures (1985) Neurology, 35, pp. 684-690 Thomas, P., Valton, P., Genton, P., Absence and myoclonic status epilepticus precipitated by antiepileptic drugs in idiopathic generalized epilepsy (2006) Brain, 129, pp. 1281-1292}, document_type={Journal Article, Case Reports, }, affiliation={Epilepsy Center, Department of Neurological Sciences, Federico II University, Naples, Italy. ledabilo@fastwebnet.it Neurology Outpatients Service, Azienda Sanitaria Locale Napoli 1, Naples, Italy Institute of Biostructure and Bioimaging, CNR, Department of Biomorphological Sciences, Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_9012, author={Pellecchia MT, Barone PB, Mollica C, Salvatore E, Ianniciello M, Longo K, Varrone A, Vicidomini C, Picillo M, De Michele G, Filla A, Salvatore M, Pappata S}, title={Diffusion-weighted imaging in multiple system atrophy: a comparison between clinical subtypes}, date={2009 Apr 15}, journal={Mov Disord (ISSN: 1531-8257, 0885-3185, 0885-3185linking)}, year={2009}, fullvolume={439}, volume={439}, pages={689--696}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-67651154396&partnerID=40&md5=4bacecd2b8790e827d0b6227dd7c1c18}, abstract={Multiple system atrophy can be classi.ed into two main types, a Parkinsonian (MSA-P) and a cerebellar (MSA-C) variant based on clinical presentation. We obtained diffusion-weighted magnetic resonance imaging (DWI) in 9 MSAP and 12 MSA-C patients and 11 controls, and correlated DWI changes with disease duration and severity. We found that Trace (D) values in the entire and anterior putamen were significantly higher in MSA-P than in MSA-C patients and controls, whereas Trace (D) values in the cerebellum and middle cerebellar peduncle (MCP) were significantly higher in MSA-C than in MSA-P patients and controls. Increased disease duration was significantly correlated with increased Trace (D) values in pons of MSA-P patients, and in cerebellum and MCP of MSA-C patients. Both UMSARS and UPDRS motor scores positively correlated with entire and posterior putaminal Trace (D) values in MSA-P patients. The diffusivity changes parallel phenotypical and pathologic differences between MSA-P and MSA-C patients, suggesting that DWI is a feasible tool for in vivo evaluation of neurodegeneration in MSA. Based on our findings, Trace (D) measurements in the putamen and pons in MSA-P patients and in the cerebellum and MCP in MSA-C patients could serve as quantitative markers for microstructural damage in the course of disease. © 2008 Movement Disorder Society.}, keywords={Diffusion-Weighted Imaging, Magnetic Resonance Imaging, Msa Subtypes, Adult, Article, Brain Region, Cerebellum Disease, Clinical Article, Controlled Study, Diffusion Weighted Imaging, Disease Classification, Disease Duration, Disease Severity, Human, Image Analysis, Middle Cerebellar Peduncle, Nuclear Magnetic Resonance Imaging, Parkinsonism, Pons, Priority Journal, Putamen, Scoring System, Shy Drager Syndrome, Analysis Of Variance, Brain Mapping, Comparative Study, Female, Hospitalization, Image Processing, Methodology, Middle Aged, Pathology, Diffusion Magnetic Resonance Imaging, Computer-Assisted, Multiple System Atrophy, Severity Of Illness Index, }, references={Wenning, G.K., Ben Shlomo, Y., Magalhaes, M., Daniel, S.E., Quinn, N.P., Clinical features and natural history of multiple system atrophy: An analysis of 100 cases (1994) Brain, 117, pp. 835-84 Kume, A., Takahashi, A., Hashizume, Y., Neuronal cell loss of the striatonigral system in multiple system atrophy (1993) J Neurol Sci, 117, pp. 33-40 Wenning, G.K., Tison, F., Ben Shlomo, Y., Daniel, S.E., Quinn, N.P., Multiple system atrophy: A review of 203 pathologically proven cases (1997) Mov Disord, 12, pp. 133-147 Wenning, G.K., Colosimo, C., Geser, F., Poewe, W., Multiple system atrophy (2004) Lancet Neurol, 3, pp. 93-103 Savoiardo, M., Strada, L., Girotti, F., Olivopontocerebellar atrophy: MR diagnosis and relationship to multisystem atrophy (1990) Radiology, 174, pp. 693-696 Schrag, A., Good, C.D., Miszkiel, K., Morris, H.R., Mathias, C.J., Lees, A.J., Quinn, N.P., Differentiation of atypical Parkinsonian syndromes with routine MRI (2000) Neurology, 54, pp. 697-702 Righini, A., Antonini, A., Ferrarini, M., Thin section MR study of the basal ganglia in the differential diagnosis between striatonigral degeneration and Parkinson disease (2002) J Comput Assist Tomogr, 26, pp. 266-271 Schocke, M.F.H., Seppi, K., Esterhammer, R., Diffusion-weighted MRI differentiates the Parkinson variant of multiple system atrophy from PD (2002) Neurology, 58, pp. 575-580 Seppi, K., Schocke, M.F.H., Esterhammer, R., Diffusion-weighted imaging discriminates progressive supranuclear palsy from PD, but not from the Parkinson variant of multiple system atrophy (2003) Neurology, 60, pp. 922-927 Nicoletti, G., Lodi, R., Condino, F., Apparent diffusion coefficient measurements of the middle cerebellar peduncle differenziate the Parkinson variant of MSA from Parkinson's disease and progressive supranuclear palsy (2006) Brain, 129, pp. 2679-2687 Paviour, D.C., Thornton, J.S., Lees, A.J., Jager, H.R., Diffusion-weighted magnetic resonance imaging differentiates Parkinsonian variant of multiple system atrophy from progressive supranuclear palsy (2007) Mov Disord, 22, pp. 60-74 Hajnal, J.V., Doran, M., Hall, A.S., MR imaging of anisotropically restricted diffusion of water in the nervous system: Technical, anatomic, and pathologic considerations (1991) J Comput Assist Tomogr, 15, pp. 1-18 Le Bihan, D., Turner, R., Douek, P., Patronas, N., Diffusion MR imaging: Clinical applications (1992) Am J Roentgenol, 159, pp. 359-362 Kanazawa, M., Shimohata, T., Terajima, K., Quantitative evaluation of brainstem involvement in multiple system atrophy by diffusion-weighted MR imaging (2004) J Neurol, 251, pp. 1121-1124 Blain, C.R.V., Barker, G.J., Jarosz, J.M., Measuring brainstem and cerebellar damage in Parkinsonian syndromes using diffusion tensor MRI (2006) Neurology, 67, pp. 2199-2205 Ito, M., Watanabe, H., Kawai, Y., Usefulness of combined fractional anisotropy and apparent diffusion coefficient values for detection of involvement in multiple system atrophy (2007) J Neurol Neurosurg Psychiatry, 78, pp. 722-728 Gilman, S., Low, P.A., Quinn, N., Consensus statement on the diagnosis of multiple system atrophy (1999) J Neurol Sci, 163, pp. 94-98 Seppi, K.M.D., Schocke, M.F.H., Prennschuetz-Schuetzenau, K., Topography of putaminal degeneration in multiple system atrophy: A diffusion magnetic resonance study (2006) Mov Disord, 21, pp. 847-865 Trojanowski, J.Q., Revesz, T., Neuropathology Working Group on MSA. Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy (2007) Neuropathol Appl Neurobiol, 33, pp. 615-620 Wenning, G.K., Seppi, K., Tison, F., Jellinger, K., A novel grading scale for striatonigral degeneration (multiple system atrophy) (2002) J Neural Transm, 109, pp. 307-320 Wenning, G. K., Ben Shlomo, Y., Magalhaes, M., Daniel, S. E., Quinn, N. P., Clinical features and natural history of multiple system atrophy: An analysis of 100 cases (1994) Brain, 117, pp. 835-84 Wenning, G. K., Tison, F., Ben Shlomo, Y., Daniel, S. E., Quinn, N. P., Multiple system atrophy: A review of 203 pathologically proven cases (1997) Mov Disord, 12, pp. 133-147 Wenning, G. K., Colosimo, C., Geser, F., Poewe, W., Multiple system atrophy (2004) Lancet Neurol, 3, pp. 93-103 Schocke, M. F. H., Seppi, K., Esterhammer, R., Diffusion-weighted MRI differentiates the Parkinson variant of multiple system atrophy from PD (2002) Neurology, 58, pp. 575-580 Paviour, D. C., Thornton, J. S., Lees, A. J., Jager, H. R., Diffusion-weighted magnetic resonance imaging differentiates Parkinsonian variant of multiple system atrophy from progressive supranuclear palsy (2007) Mov Disord, 22, pp. 60-74 Hajnal, J. V., Doran, M., Hall, A. S., MR imaging of anisotropically restricted diffusion of water in the nervous system: Technical, anatomic, and pathologic considerations (1991) J Comput Assist Tomogr, 15, pp. 1-18 Blain, C. R. V., Barker, G. J., Jarosz, J. M., Measuring brainstem and cerebellar damage in Parkinsonian syndromes using diffusion tensor MRI (2006) Neurology, 67, pp. 2199-2205 Seppi, K. M. D., Schocke, M. F. H., Prennschuetz-Schuetzenau, K., Topography of putaminal degeneration in multiple system atrophy: A diffusion magnetic resonance study (2006) Mov Disord, 21, pp. 847-865 Trojanowski, J. Q., Revesz, T., Neuropathology Working Group on MSA. Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy (2007) Neuropathol Appl Neurobiol, 33, pp. 615-620 Wenning, G. K., Seppi, K., Tison, F., Jellinger, K., A novel grading scale for striatonigral degeneration (multiple system atrophy) (2002) J Neural Transm, 109, pp. 307-320}, document_type={Journal Article, Comparative Study, Research Support, Non-U. S. Gov'T, }, affiliation={Department of Neurological Sciences, University Federico II, Naples, Italy. Institute of Biostructure and Bioimaging, CNR, University Federico II, Via Pansini 5, Edificio 10, 80131 Naples, Italy IRCCS Fondazione SDN, Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_10498, author={Vicidomini C, Comerci M, Salvatore E, Quarantelli M, Varrone A, Evangelista L, Prinster A, Morra VB, Brunetti A, Salvatore M,  Alfano B, Pappata S}, title={Combined Mri And Pet-18fdg Study In Patients With Primary Progressive (pp) And Relapsing Remitting (rr) Multiple Sclerosis (ms)}, date={2008 Jun 1}, journal={Abstract Book Of Dimi/Emil Annual Meeting 2008}, year={2008}, fullvolume={360}, volume={360}, pages={N/D--N/D}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, Abstract, Conference, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_11323, author={Sbardella G, Castellano S, Vicidomini C, Rotili D, Nebbioso A, Miceli M, Altucci L, Mai A}, title={Identification of long chain alkylidenemalonates as novel small molecule modulators of histone acetyltransferases}, date={2008 May 1}, journal={Bioorganic & Medicinal Chemistry Letters (ISSN: 0960-894x)}, year={2008}, fullvolume={283}, volume={283}, pages={2788--2792}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-42949089945&partnerID=40&md5=b6d0c9815c229669db9c72f5c256b3cc}, abstract={Pentadecylidenemalonate 1b, a simplified analogue of anacardic acid, was identified as the first mixed activator/inhibitor of histone acetyltransferases (HATs). It potentiates PCAF HAT activity while inhibiting those of p300/CBP and recombinant CBP. The remarkable apoptotic effect together with the ability to selectively acetylate histone versus non-histone substrates appoint 1b as a lead for the development of anticancer drugs. (c) 2008 Elsevier Ltd. All rights reserved.}, keywords={Anacardic Acid, Antitumor Agents, Epigenetics, Hat, Histone Acetyltransferase Modulators, Antineoplastic Agent, Histone Acetyltransferase Pcaf, Pentadecylidenemalonate, Apoptosis, Article, Controlled Study, Drug Activity, Drug Identification, Drug Inhibition, Drug Mechanism, Human, Human Cell, Acetylation, Alkadienes, Cell Cycle, Enzyme Inhibitors, Models, Chemical, P300-Cbp Transcription Factors, U937 Cells, }, references={Allis, C.D., Berger, S.L., Cote, J., Dent, S., Jenuwein, T., Kouzarides, T., Pillus, L., Zhang, Y., (2007) Cell, 131, p. 633. , A number of scientists have recently proposed to rationalize the nomenclature for all the characterized members of the families of lysine demethylases, acetyltransferases, and lysine methyltransferases. We agree with the reasons supporting this proposal, yet, to avoid confusion, in this paper we preferred to use the current nomenclature. For the new one see Lee, K.K., Workman, J.L., (2007) Nat. Rev. Mol. Cell Biol., 8, p. 284 Carrozza, M.J., Utley, R.T., Workman, J.L., Cote, J., (2003) Trends Genet., 19, p. 321 Minucci, S., Pelicci, P.G., (2006) Nat. Rev. Cancer, 6, p. 38 Peterson, C.L., Laniel, M.A., (2004) Curr. Biol., 14, pp. R546 Liu, Y., Colosimo, A.L., Yang, X.-J., Liao, D., (2000) Mol. Cell. Biol., 20, p. 5540 Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Yao, T.P., (2002) Nature, 417, p. 455 Mai, A., Massa, S., Rotili, D., Cerbara, I., Valente, S., Pezzi, R., Simeoni, S., Ragno, R., (2005) Med. Res. Rev., 25, p. 261 Richon, V.M., Emiliani, S., Verdin, E., Webb, Y., Breslow, R., Rifkind, R.A., Marks, P.A., (1998) Proc. Natl. Acad. Sci. U.S.A., 95, p. 3003 Kouzarides, T., (1999) Curr. Opin. Genet. Dev., 9, p. 40 Timmermann, S., Lehrmann, H., Polesskaya, A., Harel-Bellan, A., (2001) Cell Mol. Life Sci., 58, p. 728 Anzick, S.L., Kononen, J., Walker, R.L., Azorsa, D.O., Tanner, M.M., Guan, X.Y., Sauter, G., Meltzer, P.S., (1997) Science, 277, p. 965 Sakakura, C., Hagiwara, A., Yasuoka, R., Fujita, Y., Nakanishi, M., Masuda, K., Kimura, A., Yamagishi, H., (2000) Int. J. Cancer, 89, p. 217 Aguiar, R.C., Chase, A., Coulthard, S., Macdonald, D.H., Carapeti, M., Reiter, A., Sohal, J., Cross, N.C., (1997) Blood, 90, p. 3130 Panagopoulos, I., Fioretos, T., Isaksson, M., Isaksson, M., Samuelsson, U., Billstrom, R., Strombeck, B., Johansson, B., (2001) Hum. Mol. Genet., 10, p. 395 Muraoka, M., Konishi, M., Kikuchi-Yanoshita, R., Tanaka, K., Shitara, N., Chong, J.M., Iwama, T., Miyaki, M., (1996) Oncogene, 12, p. 1565 Gayther, S.A., Batley, S.J., Linger, L., Bannister, A., Thorpe, K., Chin, S.F., Daigo, Y., Caldas, C., (2000) Nat. Genet., 24, p. 300 Ionov, Y., Matsui, S., Cowell, J.K., (2004) Proc. Natl. Acad. Sci. U.S.A., 101, p. 1273 Lehrmann, H., Pritchard, L.L., Harel-Bellan, A., (2002) Adv. Cancer Res., 86, p. 41 Zheng, Y., Thompson, P.R., Cebrat, M., Wang, L., Devlin, M., Alani, R.M., Cole, P.A., (2004) Methods Enzymol., 376, p. 188 Lau, O.D., Kundu, T.K., Soccio, R.E., Ait-Si-Ali, S., Khalil, E.M., Vassilev, A., Wolffe, A.P., Cole, P.A., (2000) Mol. Cell, 5, p. 589 Balasubramanyam, K., Swaminathan, V., Ranganathan, A., Kundu, T.K., (2003) J. Biol. Chem., 278, p. 19134 Stimson, L., Rowlands, M.G., Newbatt, Y.M., Smith, N.F., Raynaud, F.I., Rogers, P., Bavetsias, V., Aherne, G.W., (2005) Mol. Cancer Ther., 4, p. 1521 Biel, M., Kretsovali, A., Karatzali, E., Papamatheakis, J., Giannis, A., (2004) Angew. Chem. Int. Ed., 43, p. 3974 Mai, A., Rotili, D., Tarantino, D., Ornaghi, P., Tosi, F., Vicidomini, C., Sbardella, G., Filetici, P., (2006) J. Med. Chem., 49, p. 6897 Mantelingu, K., Reddy, B.A.A., Swaminathan, V., Kishore, A.H., Siddappa, N.B., Kumar, G.V.P., Nagashankar, G., Kundu, T.K., (2007) Chem. Biol., 14, p. 645 Massa, S., Mai, A., Sbardella, G., Esposito, M., Ragno, R., Loidl, P., Brosch, G., (2001) J. Med. Chem., 44, p. 2069 Bartolini, S., Mai, A., Artico, M., Paesano, N., Rotili, D., Spadafora, C., Sbardella, G., (2005) J. Med. Chem., 48, p. 6776 Sbardella, G., Bartolini, S., Castellano, S., Artico, M., Paesano, N., Rotili, D., Spadafora, C., Mai, A., (2006) ChemMedChem, 1, p. 1073 Ragno, R., Simeoni, S., Castellano, S., Vicidomini, C., Mai, A., Caroli, A., Tramontano, A., Sbardella, G., (2007) J. Med. Chem., 50, p. 1241 Varier, R.A., Swaminathan, V., Balasubramanyam, K., Kundu, T.K., (2004) Biochem. Pharmacol., 68, p. 1215 Dess, D.B., Martin, J.C., (1991) J. Am. Chem. Soc., 113, p. 7277 Allinson, G., Bushby, R.J., Jesudason, M.V., Paillaud, J.-L., Taylor, N., (1997) J. Chem. Soc., Perkin Trans. 2, 2, p. 147 Glozak, M.A., Sengupta, N., Zhang, X., Seto, E., (2005) Gene, 363, p. 15}, document_type={Journal Article, }, affiliation={Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Via Ponte Don Melillo, 84084 Fisciano, SA, Italy Dipartimento di Studi Farmaceutici, Istituto Pasteur-Fondazione Cenci Bolognetti, Università degli Studi di Roma La Sapienza, P.le A. Moro 5, 00185 Roma, Italy Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, Vico L. De Crecchio 7, 80138 Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_11322, author={Ragno R, Simeoni S, Castellano S, Vicidomini C, Mai A, Caroli A, Tramontano  A, Bonaccini C, Trojer P, Bauer I, Brosch G, Sbardella G}, title={Small molecule inhibitors of histone arginine methyltransferases: Homology modeling, molecular docking, binding mode analysis, and biological evaluations}, date={2007 Mar 22}, journal={J Med Chem (ISSN: 0022-2623, 1520-4804, 0022-2623print)}, year={2007}, fullvolume={607}, volume={607}, pages={1241--1253}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33947685838&partnerID=40&md5=2c83b7a9085c5e8a4c1d87e49ea50df2}, abstract={The screening of the inhibition capabilities of dye-like small molecules from a focused library against both human PRMT1 and Aspergillus nidulans RmtA is reported as well as molecular modeling studies (homology modeling, molecular docking, and 3-D QSAR) of the catalytic domain of the PRMT1 fungal homologue RmtA. The good correlation between computational and biological results makes RmtA a reliable tool for screening arginine methyltransferase inhibitors. In addition, the binding mode analyses of tested derivatives reveal the crucial role of two regions, the pocket formed by Ile12, His13, Met16, and Thr49 and the SAM cisteinic binding site subsite. These regions should be taken into account in the design of novel PRMT inhibitors.}, keywords={Enzyme Inhibitor, Histone Arginine Methyltransferase, Histone Methyltransferase, Unclassified Drug, Amino Acid Sequence, Article, Aspergillus Nidulans, Binding Site, Correlation Analysis, Drug Activity, Drug Structure, Enzyme Binding, Enzyme Inhibition, Enzyme Structure, Human, Molecular Docking, Molecular Model, Nonhuman, Protein Domain, Quantitative Structure Activity Relation, Reliability, Sequence Homology, Structure Analysis, Animals, Benzoic Acids, Catalytic Domain, Databases, Ligands, Molecular Sequence Data, Naphthalenes, Protein Conformation, Protein-Arginine N-Methyltransferase, Quantitative Structure-Activity Relationship, Repressor Proteins, Sulfonic Acids, Triazines, Xanthenes, }, references={Strahl, B.D., Allis, C.D., The language of covalent histone modifications (2000) Nature, 403, pp. 41-4 Jenuwein, T., Allis, C.D., Translating the histone code (2001) Science, 293, pp. 1074-1080 Shi, Y., Lan, F., Matson, C., Mulligan, P., Whetstine, J.R., Cole, P.A., Casero, R.A., Shi, Y., Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 (2004) Cell, 119, pp. 941-953 Forneris, F., Binda, C., Vanoni, M.A., Battaglioli, E., Mattevi, A., Human histone demethylase LSD1 reads the histone code (2005) J. Biol. Chem, 280, pp. 41360-41365 Chen, Y., Yang, Y., Wang, F., Wan, K., Yamane, K., Zhang, Y., Lei, M., Crystal structure of human histone lysine-specific demethylase 1 (LSD1) (2006) Proc. Natl. Acad. Sci. U.S.A, 103, pp. 13956-13961 Stavropoulos, P., Blobel, G., Hoelz, A., Crystal structure and mechanism of human lysine-specific demethylase-1 (2006) Nat. Struct. Mol. Biol, 13, pp. 626-632 Yamane, K., Toumazou, C., Tsukada, Y., Erdjument-Bromage, H., Tempst, P., Wong, J., Zhang, Y., JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor (2006) Cell, 125, pp. 483-495 Whetstine, J.R., Nottke, A., Lan, F., Huarte, M., Smolikov, S., Chen, Z., Spooner, E., Shi, Y., Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases (2006) Cell, 125, pp. 467-481 Tsukada, Y., Fang, J., Erdjument-Bromage, H., Warren, M.E., Borchers, C.H., Tempst, P., Zhang, Y., Histone demethylation by a family of JmjC domain-containing proteins (2006) Nature, 439, pp. 811-816 Klose, R.J., Yamane, K., Bae, Y., Zhang, D., Erdjument-Bromage, H., Tempst, P., Wong, J., Zhang, Y., The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36 (2006) Nature, 442, pp. 312-316 Cloos, P.A., Christensen, J., Agger, K., Maiolica, A., Rappsilber, J., Antal, T., Hansen, K.H., Helin, K., The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3 (2006) Nature, 442, pp. 307-311 Zhang, Y., Reinberg, D., Transcription regulation by histone methylation: Interplay between different covalent modifications of the core histone tails (2001) Genes Dev, 15, pp. 2343-2360 Byvoet, P., Shepherd, G.R., Hardin, J.M., Noland, B.J., The distribution and turnover of labeled methyl groups in histone fractions of cultured mammalian cells (1972) Arch. Biochem. Biophys, 148, pp. 558-567 Baxter, C.S., Byvoet, P., Intercalating agents as probes of the spatial relationship between chromatin components (1975) Biochem. Biophys. Res. Commun, 63, pp. 286-291 Rice, J.C., Allis, C.D., Histone methylation versus histone acetylation: New insights into epigenetic regulation (2001) Curr. Opin. Cell Biol, 13, pp. 263-273 Turner, B.M., Memorable transcription (2003) Nat. Cell Biol, 5, pp. 390-393 Lee, D.Y., Teyssier, C., Strahl, B.D., Stallcup, M.R., Role of protein methylation in regulation of transcription (2005) Endocr. Rev, 26, pp. 147-170 Bedford, M.T., Richard, S., Arginine methylation an emerging regulator of protein function (2005) Mol. Cell, 18, pp. 263-272 Cook, J.R., Lee, J.H., Yang, Z.H., Krause, C.D., Herth, N., Hoffmann, R., Pestka, S., FBXO11/PRMT9, a new protein arginine methyltransferase, symmetrically dimethylates arginine residues (2006) Biochem. Biophys. Res. Commun, 342, pp. 472-481 Gary, J.D., Clarke, S., RNA and protein interactions modulated by protein arginine methylation (1998) Prog. Nucleic Acid Res. Mol. Biol, 61, pp. 65-131 Cheng, D., Yadav, N., King, R.W., Swanson, M.S., Weinstein, E.J., Bedford, M.T., Small molecule regulators of protein arginine methyltransferases (2004) J. Biol Chem, 279, pp. 23892-23899 Bartel, R.L., Borchardt, R.T., Effects of adenosine dialdehyde on S-adenosylhomocysteine hydrolase and S-adenosylmethionine-dependent transmethylations in mouse L929 cells (1984) Mol. Pharmacol, 25, pp. 418-424 Schwerk, C., Schulze-Osthoff, K., Methyltransferase inhibition induces p53-dependent apoptosis and a novel form of cell death (2005) Oncogene, 24, pp. 7002-7011 Casellas, P., Jeanteur, P., Protein methylation in animal cells. II. Inhibition of S-adenosyl-L-methionine:protein(arginine) N- methyltransferase by analogs of S-adenosyl-L-homocysteine (1978) Biochim. Biophys. Acta, Nucleic Acids Protein Synth, 519, pp. 255-268 Barbes, C., Sanchez, J., Yebra, M.J., Robert-Gero, M., Hardisson, C., Effects of sinefungin and S-adenosylhomocysteine on DNA and protein methyltransferases from Streptomyces and other bacteria (1990) FEMS Microbiol. Lett, 69, pp. 239-243 Massa, S., Mai, A., Sbardella, G., Esposito, M., Ragno, R., Loidl, P., Brosch, G., 3-(4-aroyl-1H-pyrro1-2-y1)-N-hydroxy-2-propenamides, a new class of synthetic histone deacetylase inhibitors (2001) J. Med. Chem, 44, pp. 2069-2072 Mai, A., Massa, S., Ragno, R., Esposito, M., Sbardella, G., Nocca, G., Scatena, R., Brosch, G., Binding mode analysis of 3-(4-benzoyl-1-methyl-1H-2-pyrro1yl)-N-hydroxy-2-propenamide: A new synthetic histone deacetylase inhibitor inducing histone hyperacetylation, growth inhibition, and terminal cell differentiation (2002) J. Med. Chem, 45, pp. 1778-1784 Ornaghi, P., Rotili, D., Sbardella, G., Mai, A., Filetici, P., A novel Gcn5p inhibitor represses cell growth, gene transcription and histone acetylation in budding yeast (2005) Biochem. Pharmacol, 70, pp. 911-917 Trojer, P., Dangl, M., Bauer, L., Graessle, S., Loidl, P., Brosch, G., Histone methyltransferases in Aspergillus nidulans: Evidence for a novel enzyme with a unique substrate specificity (2004) Biochemistry, 43, pp. 10834-10843 Barskii, V.E., Ivanov, V.B., Skliar Iu, E., Mikhailov, G.I., Dichlorotriazineylaminofluorescein-a new fluorochrome for cytochemical and histochemical detection of proteins] (1968) Izv. Akad. Nauk. SSSR Biol, 5, pp. 744-747 Peng, X., Yu, H., Hang, Y., Wang, J.N.N., phosgenation with triphosgene in the synthesis of direct dyes containing the ureylene group (1996) Dyes Pigm, 32, pp. 193-198 Adam, J.M., Kaser, A., Anionic disazo dyes (1988), EP 0290384Birkett, H.E., Cherryman, J.C., Chippendale, A.M., Evans, J.S.O., Harris, R.K., James, M., King, I.J., McPherson, G.J., Structural investigations of three triazines: Solution-state NMR studies of internal rotation and structural information from solid-state NMR, plus a full structure determination from powder X-ray diffraction in one case (2003) Magn. Reson. Chem, 41, pp. 324-336 Kuntz, I.D., Structure-based strategies for drug design and discovery (1992) Science, 257, pp. 1078-1082 Hillisch, A., Pineda, L.F., Hilgenfeld, R., Utility of homology models in the drug discovery process (2004) Drug Discovery Today, 9, pp. 659-669 Tramontano, A., Morea, V., Assessment of homology-based predictions in CASP5 (2003) Proteins, 53 (SUPPL. 6), pp. 352-368 Rosato, R.R., Grant, S., Histone deacetylase inhibitors in cancer therapy (2003) Cancer Biol. Ther, 2, pp. 30-37 Ragno, R., Mai, A., Massa, S., Cerbara, I., Valente, S., Bottoni, P., Scatena, R., Brosch, G., 3-(4-Aroyl-1-methyl-1H- pyrrol-2-yl)-N-hydroxy-2-propenamides as a new class of synthetic histone deacetylase inhibitors. 3. Discovery of novel lead compounds through structure-based drug design and docking studies (2004) J. Med. Chem, 47, pp. 1351-1359 Brosch, G. Aroyl-Pyrrolyl Hydroxyamides: Influence of Pyrrole C4-Phenylacetyl Substitution on Histone Deacetylase Inhibition. ChemMedChem 2006, 1, 225-237Ragno, R., Simeoni, S., Valente, S., Massa, S., Mai, A., 3-D QSAR studies on histone deacetylase inhibitors. A GOLPE/GRID approach on different series of compounds (2006) J. Chem. Inf. Model, 46, pp. 1420-1430 Kouranov, A., Xie, L., de la Cruz, J., Chen, L., Westbrook, J., Bourne, P.E., Berman, H.M., The RCSB PDB information portal for structural genomics (2006) Nucleic Acids Res, 34, pp. 302-305 Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E., The Protein Data Bank (2000) Nucleic Acids Res, 28, pp. 235-242 Zhang, X., Cheng, X., Structure of the predominant protein arginine methyltransferase PRMT1 and analysis of its binding to substrate peptides (2003) Structure, 11, pp. 509-520 Weiss, V.H., McBride, A.E., Soriano, M.A., Filman, D.J., Silver, P.A., Hogle, J.M., The structure and oligomerization of the yeast arginine methyltransferase, Hmt1 (2000) Nat. Struct. Biol, 7, pp. 1165-1171 Zhang, X., Zhou, L., Cheng, X., Crystal structure of the conserved core of protein arginine methyltransferase PRMT3 (2000) EMBO J, 19, pp. 3509-3519 Multiple sequence alignment was accomplished by the use of BioEdit software v. 7.0.1 and then manually adjusted. For reference see: Hall, T. A. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl. Acids Symp. Ser. 1999, 41, 95-98Venclovas, C., Comparative modeling in CASP5: Progress is evident, but alignment errors remain a significant hindrance (2003) Proteins, 53 (SUPPL. 6), pp. 380-388 Schwede, T., Kopp, J., Guex, N., Peitsch, M., SWISS-MODEL, C., An automated protein homology-modeling server (2003) Nucleic Acids Res, 31, pp. 3381-3385 Goodsell, D.S., Morris, G.M., Olson, A.J., Automated docking of flexible ligands: Applications of AutoDock (1996) J. Mol. Recognit, 9, pp. 1-5 Wang, R., Lai, L., Wang, S., Further development and validation of empirical scoring functions for structure-based binding affinity prediction (2002) J. Comput.-Aided Mol. Des, 16, pp. 11-26 Shoichet, B.K., Stroud, R.M., Santi, D.V., Kuntz, I.D., Perry, K.M., Structure-based discovery of inhibitors of thymidylate synthase (1993) Science, 259, pp. 1445-1450 Docking studies were not performed on non-active compounds (7b, 7c, 7d, and 20) and on compound 15 due to its large dimensions. (57) The two tautomeric forms of compound 16 (keto and enol, indicated as 16a and 16b, respectively) docked in different sitesCruciani, G., Watson, K.A., Comparative molecular field analysis using GRID force-field and GOLPE variable selection methods in a study of inhibitors of glycogen phosphorylase b (1994) J. Med. Chem, 37, pp. 2589-2601 Frohman, M.A., Dush, M.K., Martin, G.R., Rapid production of full-length cDNAs from rare transcripts: Amplification using a single gene-specific oligonucleotide primer (1988) Proc. Natl. Acad. Sci. U.S.A, 85, pp. 8998-9002 Bügl, H., Fauman, E., Staker, B., Zheng, F., Kushner, S., Saper, M., Bardwell, J., Jakob, U., RNA Methylation under Heat Shock Control (2000) Mol. Cell, 6, pp. 349-360 Woods, R. J. The Amber biomolecular simulation programs. J. Comput. Chem. 2005, 26, 1668-1688Schuttelkopf, A.W., van Aalten, D.M., PRODRG: A tool for high-throughput crystallography of protein-ligand complexes (2004) Acta Crystallogr., Sect. D: Biol. Crystallogr, 60, pp. 1355-1363 Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A.E., Berendsen, H.J., GROMACS: Fast, flexible, and free (2005) J. Comput. Chem, 26, pp. 1701-1718 Gillet, A., Sanner, M., Stoffler, D., Olson, A., Tangible interfaces for structural molecular biology (2005) Structure, 13, pp. 483-491 Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., Ferrin, T.E., UCSF Chimera-a visualization system for exploratory research and analysis (2004) J. Comput. Chem, 25, pp. 1605-1612 Goodford, P.J., A computational procedure for determining energetically favorable binding sites on biologically important macromolecules (1985) J. Med. Chem, 28, pp. 849-857 GOLPE, Multivariate Infometric Analysis Srl (1999) Viale dei Castagni, 16. , Perugia, Italy}, document_type={Journal Article, }, affiliation={Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Università degli Studi di Roma La Sapienza, P.le Aldo Moro 5, I-00185 Roma, Italy Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Via Ponte Don Melillo, I-84084 Fisciano (SA), Italy Howard Hughes Medical Institute, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, 683 Hoes Lane, Piscataway, NJ 08854, United States Division of Molecular Biology, Biocenter-Innsbruck Medical University, Fritz-Preglstrasse 3, 6020 Innsbruck, Austria}, ibbaffiliation={1}, } @article{IBB_ID_11321, author={Mai A, Rotili D, Tarantino D, Ornaghi P, Tosi F, Vicidomini C, Sbardella G, Nebbioso A, Miceli M, Altucci L, Filetici P}, title={Small-molecule inhibitors of histone acetyltransferase activity: Identification and biological properties}, date={2006 Nov 16}, journal={J Med Chem (ISSN: 0022-2623, 1520-4804, 0022-2623print)}, year={2006}, fullvolume={429}, volume={429}, pages={6897--6907}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33750989910&partnerID=40&md5=2d11e2bb1daaf2c6978d13baf41b41f1}, abstract={Starting from a yeast phenotypic screening performed on 21 compounds, we described the identification of two small molecules ( 9 and 18) able to significantly reduce the S. cerevisiae cell growth, thus miming the effect of GCN5 deletion mutant. Tested on a GCN5-dependent gene transcription assay, compounds 9 and 18 gave a high reduction of the reporter activity. In S. cerevisiae histone H3 terminal tails assay, the H3 acetylation levels were highly reduced by treatment with 0.6-1 mM 9, while 18 was effective only at 1.5 mM. In human leukemia U937 cell line, at 1 mM 9 and 18 showed effects on cell cycle ( arrest in G1 phase, 9), apoptosis ( 9), and granulocytic differentiation ( 18). When tested on U937 cell nuclear extracts to evaluate their histone acetyltransferase ( HAT) inhibitory action, both compounds were able to reduce the enzyme activity when used at 500 AM. Another quinoline, compound 22, was synthesized with the aim to improve the activity observed with 9 and 18. Tested in the HAT assay, 22 was able to reduce the HAT catalytic action at 50 and 25 AM, thereby being comparable to anacardic acid, curcumin, and MB- 3 used as references. Finally, in U937 cells, compounds 9 and 18 used at 2.5 mM were able to reduce the extent of the acetylation levels of histone H3 ( 9) and alpha-tubulin ( 9 and 18). In the same assay, 22 at lower concentration ( 100 AM) showed the same hypoacetylating effects with both histone and non-histone substrates.}, keywords={4 Hydroxy 2 Pentyl 3 Quinolinecarboxylic Acid, Alpha Tubulin, Anacardic Acid, Cell Extract, Curcumin, Enzyme Inhibitor, Histone Acetyltransferase, Histone Acetyltransferase Gcn5, Histone Acetyltransferase Inhibitor, Mb 3, Quinoline Derivative, Unclassified Drug, Acetylation, Antifungal Activity, Apoptosis, Article, Catalysis, Cell Cycle Arrest, Cell Cycle G1 Phase, Cell Differentiation, Cell Strain U937, Controlled Study, Deletion Mutant, Enzyme Activity, Enzyme Inhibition, Fungus Growth, Genetic Transcription, Granulocyte, Human, Human Cell, Nonhuman, Reference Value, Reporter Gene, Saccharomyces Cerevisiae, Antineoplastic Agents, Saccharomyces Cerevisiae Proteins, Structure-Activity Relationship, Trans-Activation (genetics), U937 Cells, }, references={Davie, J.R., Covalent modifications of histones: Expression from chromatin templates (1998) Curr. Opin. Genet. Dev., 8, pp. 173-17 Kouzarides, T., Histone acetylases and deacetylases in cell proliferation (1999) Curr. Opin. Genet. Dev., 9, pp. 40-48 Strahl, B.D., Allis, C.D., The language of covalent histone modifications (2000) Nature, 403, pp. 41-45 Pazin, M.J., Kadonaga, J.T., What's up and down with histone deacetylation and transcription? (1997) Cell, 89, pp. 325-328 Glass, C.K., Rosenfeld, M.G., The coregulator exchange in transcriptional functions of nuclear receptors (2000) Genes Dev., 14, pp. 121-141 Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F., Richmond, T.J., Crystal structure of the nucleosome core particle at 2.8 Å resolution (1998) Nature, 389, pp. 251-260 Urnov, F.D., Wolffe, A., Chromatin organization and human disease (2000) Emerging Ther. Targets, 4, pp. 665-685 Fischle, W., Wang, Y., Allis, C.D., Histone and chromatin crosstalk (2003) Curr. Opin. Cell Biol., 15, pp. 172-183 Akey, C.W., Luger, K., Histone chaperones and nucleosome assembly (2003) Curr. Opin. Struct. Biol., 13, pp. 6-14 Roth, S.Y., Denu, J.M., Allis, C.D., Histone acetyltransferases (2001) Annu. Rev. Biochem., 70, pp. 81-120 Sterner, D.E., Berger, S.L., Acetylation of histones and transcription-related factors (2000) Microbiol. Mol. Biol. Rev., 64, pp. 435-459 Marmorstein, R., Structure of histone acetyltransferases (2001) J. Mol. Biol., 311, pp. 433-444 Schiltz, R.L., Mizzen, C.A., Vassilev, A., Cook, R.G., Allis, C.D., Nakatani, Y., Overlapping but distinct patterns of histone acetylation by the human coactivators p300 and PCAF within nucleosomal substrates (1999) J. Biol. Chem., 274, pp. 1189-1192 Lau, O.D., Courtney, A.D., Vassilev, A., Marzilli, L.A., Cotter, R.J., Nakatani, Y., Cole, P.A., p300/CBP-associated factor histone acetyltransferase processing of a peptide substrate. Kinetic analysis of the catalytic mechanism (2000) J. Biol. Chem., 275, pp. 21953-21959 Grant, P.A., Duggan, L., Cote, J., Roberts, S.M., Brownell, J.E., Candau, R., Ohba, R., Workman, J.L., Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: Characterization of an Ada complex and the SAGA (Spt/Ada) complex (1997) Genes Dev., 11, pp. 1640-1650 Grant, P.A., Eberharter, A., John, S., Cook, R.G., Turner, B.M., Workman, J.L., Expanded lysine acetylation specificity of Gcn5 in native complexes (1999) J. Biol. Chem., 274, pp. 5895-5900 Liu, Y., Colosimo, A.L., Yang, X.-J., Liao, D., Adenovirus E1B 55-kilodalton oncoprotein inhibits p53 acetylation by PCAF (2000) Mol. Cell Biol., 20, pp. 5540-5553 Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Yao, T.P., HDAC6 is a microtubule-associated deacetylase (2002) Nature, 417, pp. 455-458 Mai, A., Massa, S., Rotili, D., Cerbara, I., Valente, S., Pezzi, R., Simeoni, S., Ragno, R., Histone deacetylation in epigenetics: An attractive target for anticancer therapy (2005) Med. Res. Rev., 25, pp. 261-309 Minucci, S., Pelicci, P.G., Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer (2006) Nat. Rev. Cancer, 6, pp. 38-51 Muraoka, M., Konishi, M., Kikuchi-Yanoshita, R., Tanaka, K., Shitara, N., Chong, J.M., Iwama, T., Miyaki, M., p300 gene alterations in colorectal and gastic carcinomas (1996) Oncogene, 12, pp. 1565-1569 Phillips, A.C., Vousden, K.H., Acetyltransferases and tumor suppression (2000) Breast Cancer Res., 2, pp. 244-246 Anzick, S.L., Kononen, J., Walker, R.L., Azorsa, D.O., Tanner, M.M., Guan, X.Y., Sauter, G., Meltzer, P.S., AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer (1997) Science, 277, pp. 965-969 Sakakura, C., Hagiwara, A., Yasuoka, R., Fujita, Y., Nakanishi, M., Masuda, K., Kimura, A., Yamagishi, H., Amplification and overexpression of the AIB1 nuclear receptor co-activator gene in primary gastric cancers (2000) Int. J. Cancer, 89, pp. 217-223 Aguiar, R.C., Chase, A., Coulthard, S., Macdonald, D.H., Carapeti, M., Reiter, A., Sohal, J., Cross, N.C., Abnormalities of chromosome band 8p11 in leukaemia: Two clinical syndromes can be distinguished on the basis of MOZ involvement (1997) Blood, 90, pp. 3130-3135 Panagopoulos, I., Fioretos, T., Isaksson, M., Isaksson, M., Samuelsson, U., Billstrom, R., Strombeck, B., Johansson, B., Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10 p13) (2001) Hum. Mol. Genet., 10, pp. 395-404 Puri, P.L., Sartorelli, V., Yang, X.J., Hamamori, Y., Ogryzko, V.V., Howard, B.H., Kedes, L., Levrero, M., Differential roles of p300 and PCAF acetyltransferases in muscle differentiation (1997) Mol. Cell, 1, pp. 35-45 Lehrmann, H., Pritchard, L.L., Harel-Bellan, A., Histone acetyltransferases and deacetylases in the control of cell proliferation and differentiation (2002) Adv. Cancer Res., 86, pp. 41-65 Zheng, Y., Thompson, P.R., Cebrat, M., Wang, L., Devlin, M., Alani, R.M., Cole, P.A., Selective HAT inhibitors as mechanistic tools for protein acetylation (2004) Methods Enzymol., 376, pp. 188-199 Lau, O.D., Kundu, T.K., Soccio, R.E., Ait-Si-Ali, S., Khalil, E.M., Vassilev, A., Wolffe, A.P., Cole, P.A., HATs off: Selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF (2000) Mol. Cell, 5, pp. 589-595 Balasubramanyam, K., Swaminathan, V., Ranganathan, A., Kundu, T.K., Small molecule modulators of histone acetyltransferase p300 (2003) J. Biol. Chem., 278, pp. 19134-19140 Biel, M., Kretsovali, A., Karatzali, E., Papamatheakis, J., Giannis, A., Design, synthesis and biological evaluation of a small molecule inhibitor of the histone acetyltransferase GCN5 (2004) Angew. Chem., Int. Ed., 43, pp. 3974-3976 Stimson, L., Rowlands, M.G., Newbatt, Y.M., Smith, N.F., Raynaud, F.I., Rogers, P., Bavetsias, V., Aherne, G.W., Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity (2005) Mol. Cancer Ther., 4, pp. 1521-1532 Massa, S., Mai, A., Sbardella, G., Esposito, M., Ragno, R., Loidl, P., Brosch, G., 3-(4-Aroyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamides, a new class of synthetic histone deacetylase inhibitors (2001) J. Med. Chem., 44, pp. 2069-2072 Ragno, R., Mai, A., Massa, S., Cerbara, I., Valente, S., Bottoni, P., Scatena, R., Brosch, G., 3-(4-Aroyl-1-methyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamides as a new class of synthetic histone deacetylase inhibitors. 3. Discovery of novel lead compounds through structure-based drug design and docking studies (2004) J. Med. Chem., 47, pp. 1351-1359 Georgakopoulos, T., Thireos, G., Two distinct yeast transcriptional activators require the function of the GCN5 protein to promote normal levels of transcription (1992) EMBO J., 11, pp. 4145-4152 Warrell Jr., R.P., Frankel, S.R., Miller Jr., W.H., Scheinberg, D.A., Itri, L.M., Hittelman, W.N., Vyas, R., Jakubowski, A.N., (1991) Engl. J. Med., 324, p. 1385 Man, J.W., Ahn, S.H., Park, S.H., Wang, S.Y., Bae, G.U., Seo, D.W., Known, H.K., Lee, H.W., Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumor cells via induction of p21WAF1/Cip1 and gelsolin (2000) Cancer Res., 60, pp. 6068-6074 Shute, R.E., Dunlap, B., Rich, D.H., Analogues of the cytostatic and antimitogenic agents chlamydocin and HC-toxin: Synthesis and biological activity of chloromethyl ketone and diazomethyl ketone functionalized cyclic tetrapeptides (1987) J. Med. Chem., 30, pp. 71-78 Diana, G.D., McKinlay, M.A., Otto, M.J., Akullian, V., Oglesby, C., [[(4,5-Dihydro-2-oxazolyl)phenoxy]alkyl]isoxazoles. Inhibitors of picornavirus uncoating (1985) J. Med. Chem., 28, pp. 1906-1910 Ornaghi, P., Rotili, D., Sbardella, G., Mai, A., Filetici, P., A novel Gcn5p inhibitor represses cell growth, gene transcription and histone acetylation in budding yeast (2005) Biochem. Pharmacol., 70, pp. 911-917 Ladner, D.W., Oxidation of methylquinolines with nickel peroxide (1986) Synth. Commun., 16, pp. 157-162 Ech-Chahad, A., Minassi, A., Berton, L., Appendino, G., An expeditious hydroxyamidation of carboxylic acids (2005) Tetrahedron Lett., 46, pp. 5113-5115 Mori, K., Koseki, K., Synthesis of trichostatin A, a potent differentiation inducer of Friend leukemic cells, and its antipode (1988) Tetrahedron, 44, pp. 6013-6020 Nyoung Kim, J., Mi Chung, Y., Jin Im, Y., Synthesis of quinolines from the Baylis-Hillman acetates via the oxidative cyclization of sulfonamidyl radical as the key step (2002) Tetrahedron Lett., 43, pp. 6209-6211 Ma, Z., Hano, Y., Nomura, T., Chen, Y., Novel quinazoline-quinoline alkaloids with cytotoxic and DNA topoisomerase 11 inhibitory activities (2004) Bioorg. Med. Chem. Lett., 14, pp. 1193-1196 Asao, N., Nogami, T., Lee, S., Yamamoto, Y., Lewis acid-catalyzed benzannulation via unprecedented [4 + 2] cycloaddition of o-alkynyl-(oxo)benzenes and enynals with alkynes (2003) J. Am. Chem. Soc., 125, pp. 10921-10925 Howe, L.A., Auston, D., Grant, P., John, S., Cook, R.G., Workman, J.L., Pillus, L., Histone H3 specific acetyltransferases are essential for cell cycle progression (2001) Genes Dev., 15, pp. 3144-3154 Kuo, M.-H., Zhou, J., Jambeck, P., Churcill, M.E.A., Allis, C.D., Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo (1998) Genes Dev., 12, pp. 627-639 Tanner, K.G., Trievel, L.C., Kuo, M.-H., Howard, R.M., Berger, S.L., Allis, C.D., Marmorstein, R., Denu, J.M., Catalytic mechanism and function of invariant glutamic acid 173 from the histone acetyltransferase GCN5 transcriptional coactivator (1999) J. Biol. Chem., 274, pp. 18157-18160 Roberts, S.M., Winston, F., SPT20/ADA5 encodes a novel protein functionally related to the TATA-binding protein and important for transcription in Saccharomyces cerevisiae (1996) Mol. Cell. Biol., 16, pp. 3206-3213 Sterner, D.E., Grant, P.A., Roberts, S.M., Duggan, L.J., Belotserkovskaya, R., Pacella, L.A., Winston, F., Berger, S.L., Functional organization of the yeast SAGA complex: Distinct components involved in structural integrity, nucleosome acetylation, and TATA-binding protein interaction (1999) Mol. Cell. Biol., 19, pp. 86-98 Kang, J., Chen, J., Shi, Y., Jia, J., Zhang, Y., Curcumin-induced histone hypoacetylation: The role of reactive oxygen species (2005) Biochem. Pharmacol, 69, pp. 1205-1213 Marcu, M.G., Jung, Y.-J., Lee, S., Chung, E.-J., Lee, M.-J., Trepel, J., Neckers, L., Curcumin is an inhibitor of p300 histone acetyltransferase (2006) Med. Chem., 2, pp. 169-174 Richon, V.M., Emiliani, S., Verdin, E., Webb, Y., Breslow, R., Rifkind, R.A., Marks, P.A., A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases (1998) Proc. Natl. Acad. Sci. U.S.A., 95, pp. 3003-3007 Mai, A., Esposito, M., Sbardella, G., Massa, S., A new facile and expeditious synthesis of N-hydroxy-N′- phenyloctanediamide, a potent inducer of terminal cytodifferentiation (2001) Org. Prep. Proced. Int., 33, pp. 391-394 Wach, A., Brachat, A., Pohlmann, R., Philippsen, P., New heterologous modules for classical or PCR based gene disruptions in Saccharomyces cerevisiae (1994) Yeast, 10, pp. 1793-1808 Guarente, L., Yocum, R.R., Gifford, P., A GAL10-CYC1 hybrid yeast promoter identifies the GAL4 regulatory region as an upstream site (1982) Proc. Natl Acad. Sci. U.S.A., 79, pp. 7410-7414 Bradford, M.M., A dye binding assay for protein (1976) Anal. Biochem., 72, pp. 248-254 Valenzuela, L., Ballario, P., Aranda, C., Filetici, P., Gonzalez, A., Regulation of expression of GLT1, the gene encoding glutamate synthase in Saccharomyces cerevisiae (1998) J. Bacteriol., 180, pp. 3533-3540 Kushnirov, V.V., Rapid and reliable protein extraction from yeast (2000) Yeast, 16, pp. 857-860 Altucci, L., Rossin, A., Raffelsberger, W., Reitmair, A., Chomienne, C., Gronemeyer, H., Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAIL (2001) Nat. Med., 7, pp. 680-686 Nebbioso, A., Clarke, N., Voltz, E., Germain, E., Ambrosino, C., Bontempo, P., Alvarez, R., Altucci, L., Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells (2005) Nat. Med., 11, pp. 77-84}, document_type={Journal Article, }, affiliation={Dipartimento di Studi Farmaceutici, Istituto Pasteur-Fondazione Cenci Bolognetti, Universita degli Studi di Roma La Sapienza, P.le A. Moro 5, 00185 Roma, Italy Dipartimento di Genetica e Biologia Molecolare, Università degli Studi di Roma La Sapienza, P.le A. Moro 5, 00185 Roma, Italy Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, Vico L. De Crecchio 7, 80138 Napoli, Italy Centro di Oncogenomica AIRC, CEINGE Biotecnologia Avanzata, Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_11320, author={Mai A, Rotili D, Ornaghi P, Tosi F, Vicidomini C, Sardella G, Nebbioso A, Altucci L, Filatici P}, title={Identification of small molecules inhibitors of GCN5 histone acetyltransferase activity}, date={2006}, journal={Arkivoc (ISSN: 1424-6376)}, year={2006}, fullvolume={250}, volume={250}, pages={24--37}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33744470562&partnerID=40&md5=736f517cf4e92d098c00f595b4211328}, abstract={Starting from a yeast phenotypic screening performed on 21 chemically different substances we described the discovery of two small molecules as GCN5 inhibitors. The 2-methyl-3-carbethoxyquinoline 9 and its 2-desmethyl analogue 18 were able to significantly reduce the yeast cell growth, thus miming the effect of GCN5 deletion mutant. Tested to evaluate their effect on GCN5-dependent transcription of the HIS3 gene, 9 and 18 showed high inhibitory activity of gene transcription, more evident in activated conditions. Compound 9 was also able to reduce the acetylation levels of H3 and, to a lesser extent, H4 in yeast at 0.6 mM. In human leukemia U937 cells, at 1 mM concentration 9 showed 27% apoptosis induction, while 18 had just a little effect in the same conditions. Further studies on 9 and 18 will be performed to deepen their effects on GCN5-related phenomena.}, keywords={Acetylation, Chromatin Remodelling, Gcn5, Yeast, }, references={Davie, J.R., (1998) Curr. Opin. Genet. Dev., 8, p. 17 Kouzarides, T., (1999) Curr. Opin. Genet. Dev., 9, p. 40 Strahl, B.D., Allis, C.D., (2000) Nature, 403, p. 41 Pazin, M.J., Kadonaga, J.T., (1997) Cell, 89, p. 325 Glass, C.K., Rosenfeld, M.G., (2000) Genes Dev., 14, p. 121 Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F., Richmond, T.J., (1998) Nature, 389, p. 251 Urnov, F.D., Wolffe, A., (2000) Emerg. Ther. Targets, 4, p. 665 Fischle, W., Wang, Y., Allis, C.D., (2003) Curr. Opin. Cell Biol., 15, p. 172 Akey, C.W., Luger, K., (2003) Curr. Opin. Struc. Biol., 13, p. 6 Roth, S.Y., Denu, J.M., Allis, C.D., (2001) Annu. Rev. Biochem., 70, p. 81 Sterner, D.E., Berger, S.L., (2000) Microbiol. Mol. Biol. Rev., 64, p. 435 Marmorstein, R., (2001) J. Mol. Biol., 311, p. 433 Schiltz, R.L., Mizzen, C.A., Vassilev, A., Cook, R.G., Allis, C.D., Nakatani, Y., (1999) J. Biol. Chem., 274, p. 1189 Lau, O.D., Courtney, A.D., Vassilev, A., Marzilli, L.A., Cotter, R.J., Nakatani, Y., Cole, P.A., (2000) J. Biol. Chem., 275, p. 21953 Grant, P.A., Duggan, L., Cote, J., Roberts, S.M., Brownell, J.E., Candau, R., Ohba, R., Workman, J.L., (1997) Genes Dev., 11, p. 1640 Grant, P.A., Eberharter, A., John, S., Cook, R.G., Turner, B.M., Workman, J.L., (1999) J. Biol. Chem., 274, p. 5895 Mai, A., Massa, S., Rotili, D., Cerbara, I., Valente, S., Pezzi, R., Simeoni, S., Ragno, R., (2005) Med. Res. Rev., 25, p. 261 Minucci, S., Pelicci, P.G., (2006) Nat. Rev. Cancer, 6, p. 38 Muraoka, M., Konishi, M., Kikuchi-Yanoshita, R., Tanaka, K., Shitara, N., Chong, J.M., Iwama, T., Miyaki, M., (1996) Oncogene, 12, p. 1565 Sakakura, C., Hagiwara, A., Yasuoka, R., Fujita, Y., Nakanishi, M., Masuda, K., Kimura, A., Yamagishi, H., (2000) Int. J. Cancer, 89, p. 217 Puri, P.L., Sartorelli, V., Yang, X.J., Hamamori, Y., Ogryzko, V.V., Howard, B.H., Kedes, L., Levrero, M., (1997) Mol. Cell, 1, p. 35 Lehrmann, H., Pritchard, L.L., Harel-Bellan, A., (2002) Adv. Cancer Res., 86, p. 41 Zheng, Y., Thompson, P.R., Cebrat, M., Wang, L., Devlin, M.K., Alani, R.M., Cole, P.A., (2004) Methods Enzymol., 376, p. 188 Lau, O.D., Kundu, T.K., Soccio, R.E., Ait-Si-Ali, S., Khalil, E.M., Vassilev, A., Wolffe, A.P., Cole, P.A., (2000) Mol. Cell, 5, p. 589 Balasubramanyam, K., Swaminathan, V., Ranganathan, A., Kundu, T.K., (2003) J. Biol. Chem., 278, p. 19134 Biel, M., Kretsovali, A., Karatzali, E., Papamatheakis, J., Giannis, A., (2004) Angew. Chem. Int. Ed., 43, p. 3974 Stimson, L., Rowlands, M.G., Newbatt, Y.M., Smith, N.F., Raynaud, F.I., Rogers, P., Bavetsias, V., Aherne, G.W., (2005) Mol. Cancer Ther., 4, p. 1521 Massa, S., Mai, A., Sbardella, G., Esposito, M., Ragno, R., Loidl, P., Brosch, G., (2001) J. Med. Chem., 44, p. 2069 Ragno, R., Mai, A., Massa, S., Cerbara, I., Valente, S., Bottoni, P., Scatena, R., Brosch, G., (2004) J. Med. Chem., 47, p. 1351 Warrell Jr., R.P., Frankel, S.R., Miller Jr., W.H., Scheinberg, D.A., Itri, L.M., Hittelman, W.N., Vyas, R., Jakubowski, A.N., (1991) Engl. J. Med., 324, p. 1385 Han, J.W., Ahn, S.H., Park, S.H., Wang, S.Y., Bae, G.U., Seo, D.W., Known, H.K., Lee, H.W., (2000) Cancer Res., 60, p. 6068 Shute, R.E., Dunlap, B., Rich, D.H., (1987) J. Med. Chem., 30, p. 71 Ornaghi, P., Rotili, D., Sbardella, G., Mai, A., Filetici, P., (2005) Biochem. Pharmacol., 70, p. 911 Diana, G.D., McKinlay, M.A., Otto, M.J., Akullian, V., Oglesby, C., (1985) J. Med. Chem., 28, p. 1906 Ladner, D.W., (1986) Synthetic Commun., 16, p. 157 Ech-Chahad, A., Minassi, A., Berton, L., Appendino, G., (2005) Tetrahedron Lett., 46, p. 5113 Mori, K., Koseki, K., (1988) Tetrahedron, 44, p. 6013 Nyoung Kim, J., Mi Chung, Y., Jin Im, Y., (2002) Tetrahedron Lett., 43, p. 6209 Ma, Z., Hano, Y., Nomura, T., Chen, Y., (2004) Bioorg. Med. Chem. Lett., 14, p. 1193 Asao, N., Nogami, T., Lee, S., Yamamoto, Y., (2003) J. Amer. Chem. Soc., 125, p. 10921 Howe, L.A., Auston, D., Grant, P., John, S., Cook, R.G., Workman, J.L., Pillus, L., (2001) Genes Dev., 15, p. 3144}, document_type={Journal Article, }, affiliation={Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Universit degli Studi di Roma La Sapienza, P. le A. Moro 5, 00185 Roma, Italy Dipartimento di Genetica e Biologia Molecolare, Universit degli Studi di Roma La Sapienza, P. le A. Moro 5, 00185 Roma, Italy Dipartimento di Scienze Farmaceutiche, Universit degli Studi di Salerno, via Ponte Don Melillo, 84084 Fisciano (SA), Italy Dipartimento di Patologia Generale, Seconda Universit degli Studi di Napoli, vico L. De Crecchio 7, 80138 Napoli, Italy Centro di Oncogenomica AIRC, CEINGE Biotecnologia Avanzata, Napoli, Italy Istituto di Biologia e Patologia Molecolari CNR, Dip. Genetica e Biologia Molecolare, Universit degli Studi di Roma La Sapienza, P. le A. Moro 5, 00185 Roma, Italy}, ibbaffiliation={1}, } @article{IBB_ID_11319, author={Paesano N, Marzocco S, Vicidomini C, Saturnino C, Autore G, De Martino G, Sbardella G}, title={Synthesis and biological evaluation of 3-benzyl-1-methyl- and 1-methyl-3-phenyl-isothioureas as potential inhibitors of iNOS}, date={2005 Feb 1}, journal={Bioorganic & Medicinal Chemistry Letters (ISSN: 0960-894x)}, year={2005}, fullvolume={399}, volume={399}, pages={539--543}, url={}, abstract={Novel benzyl- and phenyl-isothioureidic derivatives have been synthesised and evaluated as inhibitors of nitric oxide synthesis. induced in lipopolysaccharide (LPS)-activated J774.A1 macrophage cell line. The most potent iNOS inhibitor resulting was 1-methyl-3-phenyl-S-methyl isothiourea 5I. (C) 2004 Elsevier Ltd. All rights reserved.}, keywords={Inos, Isothioureas, Nitric Oxide, 1 Methyl 3 Phenylisothiourea, 3 Benzyl 1 Methylisothiourea, Lipopolysaccharide, Nitric Oxide Synthase Inhibitor, Pseudothiourea Derivative, Unclassified Drug, Animal Cell, Article, Cell Line, Controlled Study, Drug Synthesis, Evaluation, Macrophage, Mouse, Nonhuman, Dose-Response Relationship, Enzyme Inhibitors, Mice, Nitric Oxide Synthase Type Ii, Structure-Activity Relationship, }, references={Alderton, W.K., Cooper, C.E., Knowles, R.G., (2001) Biochem. J., 357, pp. 593-61 Boughton-Smith, N.K., Tinker, A.C., (1998) IDrugs, 1, pp. 321-333 Cochran, F.R., Selph, J., Sherman, P., (1996) Med. Res. Rev., 16, pp. 547-563 Cheshire, D.R., (2001) IDrugs, 4, pp. 795-803 Salvemini, D., Wang, Z.-Q., Wyatt, P.S., Bourdon, D.M., Marino, M.H., Manning, P.T., Currie, M.G., (1996) Br. J. Pharmacol., 118, pp. 829-838 Moore, W.M., Webber, R.K., Jerome, G.M., Tjoeng, F.S., Misko, T.P., Currie, M.G., (1994) J. Med. Chem., 37, pp. 3886-3888 Hansel, T.T., Kharotinov, S.A., Donelly, L.A., Erin, E.M., Currie, M.G., Moore, W.M., Manning, P.T., Barnes, P.J., (2003) FASEB J., 17, pp. 1298-1300 Young, R.J., Beams, R.M., Carter, K., Clark, H.A.R., Coe, D.M., Chambers, C.L., Davies, P.I., Knowles, G., (2000) Bioorg. Med. Chem. Lett., 10, pp. 597-600 Olken, N.M., Rusche, K.M., Richards, M.K., Marletta, M.A., (1991) Biochem. Biophys. Res. Commun., 177, pp. 828-833 Furfine, E.S., Harmon, M.F., Paith, J.E., Garvey, E.P., (1993) Biochemistry, 32, pp. 8512-8517 Ruetten, H., Thiemermann, C., (2000) Nitric Oxide and Septic Shock in Nitric Oxide, pp. 747-757. , L.J. Ignarro Academic San Diego Nussler, A.K., Billiar, T.A., (1993) J. Leukocyte Biol., 54, p. 171 Corbett, J.A., Tilton, R.G., Chang, K., Hasan, K.S., Ido, Y., Wang, J.L., Sweetland, M.A., McDaniel, M.L., (1992) Diabetes, 41, p. 552 Joly, G.A., Ayres, M., Chelly, F., Kilbourn, R.G., (1994) Biochem. Biophys. Res. Commun., 199, p. 147 Nakane, M., Klinghofer, V., Kuk, J.E., Donnelly, J.L., Budzik, G.P., Pollock, J.S., Basha, F., Carter, G.E., (1995) Mol. Pharmacol., 47, p. 831 Garvey, E.P., Oplinger, J.A., Tanoury, G.J., Sherman, P.A., Fowler, M., Marshall, S., Harmon, M.F., Furfine, E.S., (1994) J. Biol. Chem., 269, p. 26669 Shankaran, K., Donnelly, K.L., Shah, S.K., Humes, J.L., Pacholok, S., Green, B.G., Grant, S.K., MacCoss, M., (1997) Bioorg. Med. Chem. Lett., 7, p. 2887 Hagmann, W.K., Caldwell, C.G., Chen, P., Durette, P., Esser, C.K., Lanza, T.J., Kopka, I.E., Wong, K.K., (2000) Bioorg. Med. Chem. Lett., 10, p. 1975 Ueda, S., Terauchi, H., Yano, A., Ido, M., Matsumoto, M., Kawasaki, M., (2004) Bioorg. Med. Chem. Lett., 14, p. 313 Saturnino, C., D'Auria, M., Paesano, N., Saponiero, D., Cioffi, G., Buonerba, M., De Martino, G., (2003) Farmaco, 58, pp. 823-828 Saturnino, C., Buonerba, M., Paesano, N., Lancelot, J.-C., De Martino, G., (2003) Farmaco, 58, pp. 819-822 noteOlszanecki, R., Marcinkiewicz, J., (2004) Amino Acids, 27, pp. 29-35 Marzocco, S., Piacente, S., Pizza, C., Oleszek, W., Stochmal, A., Pinto, A., Sorrentino, R., Autore, G., (2004) Life Sci., 75, pp. 1491-1501 Green, L.C., Wagner, D.A., Glogowski, J., Skipper, P.L., Wishnok, J.J., Tannebaum, S.R., (1982) Anal. Biochem., 126, pp. 131-138 noteUR - http://www.scopus.com/inward/record.url?eid=2-s2.0-12444284865&partnerID=40&md5=a153b6ca183394427bbf06d94476cdc6}, document_type={Journal Article, }, affiliation={Dipto. di Scienze Farmaceutiche, Univ. degli Studi di Salerno, via Ponte Don Melillo, 84084 Fisciano, Salerno, Italy}, ibbaffiliation={1}, }