Keywords: Clioquinol, Copper, Cyclodipeptides, Drug Repurposing, Metallostasis, Metformin, Neurodegenerative Diseases, Chelating Agent, Cyclopeptide, Central Nervous System Agents, Alzheimer Disease, Drug Repositioning, Human, Neuroprotection, Nonhuman, Review, Chemistry, Pharmacology, Drug Therapy,
Affiliations: *** IBB - CNR ***
National Research Council of Italy - Department of Biomedical Sciences Catania. Italy.,
Institute of Biostructure and Bioimaging, National Council of Research, Via Gaifami, Catania, 18-95125, Italy
Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche, Catania, Italy.,
References: Frausto Da Silva, J.J., Williams, R.J., (2001) Biolog. Chem. Elem., , (2nd ed.), 2nd e
Luk, E., Jensen, L.T., Culotta, V.C., The many highways for intracellular trafficking of metals (2003) J. Biol. Inorg. Chem., 8 (8), pp. 803-809
Tomasello, M.F., Sinopoli, A., Pappalardo, G., On the environmental factors affecting the structural and cytotoxic properties of IAPP peptides (2015) J. Diabetes Res., 2015, pp. 1-15
Ayton, S., Lei, P., Bush, A.I., Metallostasis in Alzheimer’s disease (2013) Free Radic. Biol. Med., 62, pp. 76-89
Tisato, F., Marzano, C., Porchia, M., Pellei, M., Santini, C., Copper in diseases and treatments, and copper-based anticancer strategies (2010) Med. Res. Rev., 30 (4), pp. 708-749
Keen, C.L., Hanna, L.A., Lanoue, L., Uriu-Adams, J.Y., Rucker, R.B., Clegg, M.S., Developmental consequences of trace mineral deficiencies in rodents: Acute and long-term effects (2003) J. Nutr., 133 (5), pp. 1477S-1480S
Tamano, H., Takeda, A., Is interaction of amyloid β - peptides with metals involved in cognitive activity? (2015) Metallomics, 7 (8), pp. 1205-1212
Damante, C.A., Osz, K., Nagy, Z., Pappalardo, G., Grasso, G., Impellizzeri, G., Rizzarelli, E., Sóvágó, I., The metal loading ability of beta-amyloid N-terminus: A combined potentiometric and spectroscopic study of copper(II) complexes with beta-amyloid(1-16), its short or mutated peptide fragments, and its polyethylene glycol (PEG)-ylated analogue (2008) Inorg. Chem., 47 (20), pp. 9669-9683
Kozlowski, H., Luczkowski, M., Remelli, M., Valensin, D., Copper, zinc and iron in neurodegenerative diseases (Alzheimer’s, Parkinson’s and prion diseases) (2012) Coord. Chem. Rev., 256 (19-20), pp. 2129-2141
Lutsenko, S., Copper trafficking to the secretory pathway (2016) Metallomics, 8 (9), pp. 840-852
Greenough, M.A., Ramírez Munoz, A., Bush, A.I., Opazo, C.M., Metallo-pathways to Alzheimer’s disease: Lessons from genetic disorders of copper trafficking (2016) Metallomics, 8 (9), pp. 831-839
Greenough, M.A., Camakaris, J., Bush, A.I., Metal dy-shomeostasis and oxidative stress in Alzheimer’s disease (2013) Neurochem. Int., 62 (5), pp. 540-555
Porter, M.R., Kochi, A., Karty, J.A., Lim, M.H., Zaleski, J.M., Chelation-induced diradical formation as an approach to modulation of the amyloid-β aggregation pathway (2015) Chem. Sci. (Camb.), 6, pp. 1018-1026
He, G., Luo, W., Li, P., Remmers, C., Netzer, W.J., Hendrick, J., Bettayeb, K., Greengard, P., Gamma-secretase activating protein is a therapeutic target for Alzheimer’s disease (2010) Nature, 467 (7311), pp. 95-98
Gardner, L.E., White, J.D., Eimerbrink, M.J., Boehm, G.W., Chumley, M.J., Imatinib methanesulfonate reduces hyperphosphorylation of tau following repeated peripheral exposure to lipopolysaccharide (2016) Neuroscience, 331, pp. 72-77
Alvarez, A.R., Klein, A., Castro, J., Cancino, G.I., Amigo, J., Mosqueira, M., Vargas, L.M., Zanlungo, S., Imatinib therapy blocks cerebellar apoptosis and improves neurological symptoms in a mouse model of niemann-pick type c disease (2008) FASEB J., 22 (10), pp. 3617-3627
Nam, K.N., Mounier, A., Fitz, N.F., Wolfe, C., Schug, J., Lefterov, I., Koldamova, R., RXR controlled regulatory networks identified in mouse brain counteract deleterious effects of aβ oligomers (2016) Sci. Rep., 6, p. 24048
Riancho, J., Berciano, M.T., Berciano, J., Lafarga, M., Relaunching an old drug: The potential role of bexarotene in neurodegenerative diseases (2016) J. Neurol., 263 (1), pp. 177-178
Bar-Am, O., Amit, T., Youdim, M.B., Weinreb, O., Neuroprotective and neurorestorative potential of propargylamine derivatives in ageing: Focus on mitochondrial targets (2016) J. Neural Transm. (Vienna), 123 (2), pp. 125-135
Olanow, C.W., Rascol, O., Hauser, R., Feigin, P.D., Jankovic, J., Lang, A., Langston, W., Tolosa, E., A double-blind, delayed-start trial of rasagiline in Parkinson’s disease (2009) N. Engl. J. Med., 361 (13), pp. 1268-1278
Liu, W., Lang, M., Youdim, M.B., Amit, T., Sun, Y., Zhang, Z., Wang, Y., Weinreb, O., Design, synthesis and evaluation of novel dual monoamine-cholinesterase inhibitors as potential treatment for Alzheimer’s disease (2016) Neuropharmacology, 109, pp. 376-385
Oliveri, V., Vecchio, G., 8-hydroxyquinolines in medicinal chemistry: A structural perspective (2016) Eur. J. Med. Chem., 120, pp. 252-274
Stoilova, T., Colombo, L., Forloni, G., Tagliavini, F., Salmona, M., A new face for old antibiotics: Tetracyclines in treatment of amyloidoses (2013) J. Med. Chem., 56 (15), pp. 5987-6006
Santa-Cecília, F.V., Socias, B., Ouidja, M.O., Sepulveda-Diaz, J.E., Acuña, L., Silva, R.L., Michel, P.P., Raisman-Vozari, R., Doxycycline suppresses microglial activation by inhibiting the p38 MAPK and NF-kB signaling pathways (2016) Neurotox. Res., 29 (4), pp. 447-459
Domercq, M., Matute, C., Neuroprotection by tetracyclines (2004) Trends Pharmacol. Sci., 25 (12), pp. 609-612
Lenzi, J., Pagani, F., De Santis, R., Limatola, C., Bozzoni, I., Di Angelantonio, S., Rosa, A., Differentiation of control and ALS mutant human iPSCs into functional skeletal muscle cells, a tool for the study of neuromuscolar diseases (2016) Stem Cell Res. (Amst.), 17 (1), pp. 140-147
Budni, J., Garcez, M.L., De Medeiros, J., Cassaro, E., Bellettini-Santos, T., Mina, F., Quevedo, J., The anti-inflammatory role of minocycline in Alzheimer´s disease (2016) Curr. Alzheimer Res., 13 (12), pp. 1319-1329
Van Eldik, L.J., Carrillo, M.C., Cole, P.E., Feuerbach, D., Greenberg, B.D., Hendrix, J.A., Kennedy, M., Bales, K., The roles of inflammation and immune mechanisms in Alzheimer’s disease (2016) Alzheimers Dement (NY), 2 (2), pp. 99-109
De Virgilio, A., Greco, A., Fabbrini, G., Inghilleri, M., Rizzo, M.I., Gallo, A., Conte, M., De Vincentiis, M., Parkinson’s disease: Autoimmunity and neuroinflammation (2016) Autoimmun. Rev., 15 (10), pp. 1005-1011
Olson, K.E., Gendelman, H.E., Immunomodulation as a neuroprotective and therapeutic strategy for Parkinson’s disease (2016) Curr. Opin. Pharmacol., 26, pp. 87-95
Möller, T., Bard, F., Bhattacharya, A., Biber, K., Campbell, B., Dale, E., Eder, C., Boddeke, H.W., Critical data-based re-evaluation of minocycline as a putative specific microglia inhibitor (2016) Glia, 64 (10), pp. 1788-1794
Caccamo, D., Pisani, L.R., Mazzocchetti, P., Ientile, R., Calabresi, P., Pisani, F., Costa, C., Neuroprotection as a potential therapeutic perspective in neurodegenerative diseases: Focus on antiepileptic drugs (2016) Neurochem. Res., 41 (1-2), pp. 340-352
Deardorff, W.J., Grossberg, G.T., Targeting neuroinflammation in Alzheimer’s disease: Evidence for NSAIDs and novel therapeutics (2017) Expert Rev. Neurother., 17 (1), pp. 17-32
Lee, Y.-I., Kang, H., Ha, Y.W., Chang, K.-Y., Cho, S.-C., Song, S.O., Kim, H., Shin, J.-H., Diaminodiphenyl sulfone-induced parkin ameliorates age-dependent dopaminergic neuronal loss (2016) Neurobiol. Aging, 41, pp. 1-10
Diack, A.B., Alibhai, J.D., Barron, R., Bradford, B., Piccardo, P., Manson, J.C., Insights into mechanisms of chronic neurodegeneration (2016) Int. J. Mol. Sci., 17 (1), p. E82
Chiang, M.-C., Nicol, C.J., Cheng, Y.-C., Lin, K.-H., Yen, C.H., Lin, C.-H., Rosiglitazone activation of PPARγ-dependent pathways is neuroprotective in human neural stem cells against amyloid-beta-induced mitochondrial dysfunction and oxidative stress (2016) Neurobiol. Aging, 40, pp. 181-190
Normando, E.M., Davis, B.M., De Groef, L., Nizari, S., Turner, L.A., Ravindran, N., Pahlitzsch, M., Cordeiro, M.F., The retina as an early biomarker of neurodegeneration in a rotenone-induced model of Parkinson’s disease: Evidence for a neuroprotective effect of rosiglitazone in the eye and brain (2016) Acta Neuropathol. Commun., 4 (1), p. 86
Díaz-Alonso, J., Paraíso-Luna, J., Navarrete, C., Del Río, C., Cantarero, I., Palomares, B., Aguareles, J., Muñoz, E., VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of huntington’s disease (2016) Sci. Rep., 6, p. 29789
Corona, J.C., Duchen, M.R., PPARγ as a therapeutic target to rescue mitochondrial function in neurological disease (2016) Free Radic. Biol. Med., 100, pp. 153-163
Hansen, H.H., Fabricius, K., Barkholt, P., Kongsbak-Wismann, P., Schlumberger, C., Jelsing, J., Terwel, D., Vrang, N., Long-term treatment with liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has no effect on β -amyloid plaque load in two transgenic APP/PS1 mouse models of Alzheimer’s disease (2016) PLoS One, 11 (7), p. e0158205
Qi, L., Ke, L., Liu, X., Liao, L., Ke, S., Liu, X., Wang, Y., Liu, L., Subcutaneous administration of liraglutide ameliorates learning and memory impairment by modulating tau hyperphosphorylation via the glycogen synthase kinase-3β pathway in an amyloid β protein induced Alzheimer disease mouse model (2016) Eur. J. Pharmacol., 783, pp. 23-32
Olmos-Alonso, A., Schetters, S.T., Sri, S., Askew, K., Mancuso, R., Vargas-Caballero, M., Holscher, C., Gomez-Nicola, D., Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology (2016) Brain, 139, pp. 891-907
Ji, C., Xue, G.-F., Lijun, C., Feng, P., Li, D., Li, L., Li, G., Hölscher, C., A novel dual GLP-1 and GIP receptor agonist is neuroprotective in the MPTP mouse model of Parkinson’s disease by increasing expression of BNDF (2016) Brain Res., 1634, pp. 1-11
Fedele, E., Ricciarelli, R., Rebosio, C., Glucagon-like peptide 1, neuroprotection and neurodegenerative disorders (2016) J. Biomol. Res. Ther., 5, p. e151
Kamble, M., Gupta, R., Rehan, H.S., Gupta, L.K., Neurobehavioral effects of liraglutide and sitagliptin in experimental models (2016) Eur. J. Pharmacol., 774, pp. 64-70
Giudetti, A.M., Romano, A., Lavecchia, A.M., Gaetani, S., The role of brain cholesterol and its oxidized products in Alzheimer’s disease (2016) Curr. Alzheimer Res., 13 (2), pp. 198-205
Leduc, V., Théroux, L., Dea, D., Dufour, R., Poirier, J., Effects of rs3846662 variants on HMGCR mRNA and protein levels and on markers of Alzheimer’s disease pathology (2016) J. Mol. Neurosci., 58 (1), pp. 109-119
Ostrowski, S.M., Johnson, K., Siefert, M., Shank, S., Sironi, L., Wolozin, B., Landreth, G.E., Ziady, A.G., Simvas-tatin inhibits protein isoprenylation in the brain (2016) Neuroscience, 329, pp. 264-274
Lin, K.-D., Yang, C.-Y., Lee, M.-Y., Ho, S.-C., Liu, C.-K., Shin, S.-J., Statin therapy prevents the onset of Parkinson disease in patients with diabetes (2016) Ann. Neurol., 80 (4), pp. 532-540
Shalaby, S.Y., Louis, E.D., Statin use and its association with essential tremor and Parkinson’s disease (2016) Neuroepide-Miology, 47 (1), pp. 11-17
Saavedra, J.M., Evidence to consider angiotensin II receptor blockers for the treatment of early Alzheimer’s disease (2016) Cell. Mol. Neurobiol., 36 (2), pp. 259-279
Ashby, E.L., Miners, J.S., Kehoe, P.G., Love, S., Effects of hypertension and anti-hypertensive treatment on amyloid-β (Aβ) plaque load and aβ-synthesizing and aβ-degrading enzymes in frontal cortex (2016) J. Alzheimer’S Dis., 50 (4), pp. 1191-1203
Zhang, H., Tong, R., Bai, L., Shi, J., Ouyang, L., Emerging targets and new small molecule therapies in Parkinson’s disease treatment (2016) Bioorg. Med. Chem., 24 (7), pp. 1419-1430
Tsuruoka, Y., Takahashi, M., Suzuki, M., Sato, K., Shirayama, Y., Utility of the neurobehavioral cognitive status examination (COGNISTAT) in differentiating between depressive states in late-life depression and late-onset Alzheimer’s disease: A preliminary study (2016) Ann. Gen. Psychiatry, 15, p. 3
Broen, M.P., Leentjens, A.F., Köhler, S., Kuijf, M.L., McDonald, W.M., Richard, I.H., Trajectories of recovery in depressed Parkinson’s disease patients treated with paroxet-ine or venlafaxine (2016) Parkinsonism Relat. Disord., 23, pp. 80-85
Jellinger, K.A., Recent advances in multiple system atrophy (2016) J. Neurol. Neuromed., 1, pp. 6-17
Calvo-Rodríguez, M., García-Durillo, M., Villalobos, C., Núñez, L., Aging enables Ca2+ overload and apoptosis induced by amyloid-β oligomers in rat hippocampal neurons: Neuroprotection by non-steroidal anti-inflammatory drugs and r-flurbiprofen in aging neurons (2016) J. Alzheimers Dis., 54 (1), pp. 207-221
Park, S.A., Chevallier, N., Tejwani, K., Hung, M.M., Maruyama, H., Golde, T.E., Koo, E.H., Deficiency in either COX-1 or COX-2 genes does not affect amyloid beta protein burden in amyloid precursor protein transgenic mice (2016) Biochem. Biophys. Res. Commun., 478 (1), pp. 286-292
Zerovnik, E., Kopitar Jerala, N., Recent developments in treating Alzheimer’s disease (2016) J. Alzheimer’S Dis. Park., 6 (2)
Villa, V., Thellung, S., Corsaro, A., Novelli, F., Tasso, B., Colucci-D’Amato, L., Gatta, E., Florio, T., Celecoxib inhibits prion protein 90-231-mediated proinflammatory responses in microglial cells (2016) Mol. Neurobiol., 53 (1), pp. 57-72
Hauser, R., Dzyngel, B., Bilbault, T., Shill, H., Argo, A., Efficacy of sublingual apomorphine (APL-130277) for the treatment of OFF episodes in patients with Parkinson’s disease (P2.335) (2016) Neurology, 86 (16), pp. P2-P335
Yin, Y.W., Chang, F.C., Mahant, N., Fung, V.S., Tsui, D., Aldaajani, Z., Adam, R., Hely, M., 2. Antecollis associated with Parkinson’s disease improved following apomorphine therapy (2016) Clin. Neurophysiol., 127 (3), pp. e10-e11
Yan, R., Fan, Q., Zhou, J., Vassar, R., Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer’s disease (2016) Neurosci. Biobehav. Rev., 65, pp. 326-340
Ji, L., Zhao, X., Lu, W., Zhang, Q., Hua, Z., Intracellular aβ and its pathological role in Alzheimer’s disease: Lessons from cellular to animal models (2016) Curr. Alzheimer Res., 13 (6), pp. 621-630
Tartaglione, A.M., Armida, M., Potenza, R.L., Pezzola, A., Popoli, P., Calamandrei, G., Aberrant self-grooming as early marker of motor dysfunction in a rat model of huntington’s disease (2016) Behav. Brain Res., 313, pp. 53-57
Scannell, J.W., Blanckley, A., Boldon, H., Warrington, B., Diagnosing the decline in pharmaceutical r&D efficiency (2012) Nat. Rev. Drug Discov., 11 (3), pp. 191-200
Ashburn, T.T., Thor, K.B., Drug repositioning: Identifying and developing new uses for existing drugs (2004) Nat. Rev. Drug Discov., 3 (8), pp. 673-683
Strittmatter, S.M., Overcoming drug development bottlenecks with repurposing: Old drugs learn new tricks (2014) Nat. Med., 20 (6), pp. 590-591
Shineman, D.W., Alam, J., Anderson, M., Black, S.E., Carman, A.J., Cummings, J.L., Dacks, P.A., Fillit, H.M., Overcoming obstacles to repurposing for neurodegenerative disease (2014) Ann. Clin. Transl. Neurol., 1 (7), pp. 512-518
Arrowsmith, J., Miller, P., Trial watch: Phase II and phase III attrition rates 2011-2012 (2013) Nat. Rev. Drug Discov., 12 (8), p. 569
DiMasi, J.A., Feldman, L., Seckler, A., Wilson, A., Trends in risks associated with new drug development: Success rates for investigational drugs (2010) Clin. Pharmacol. Ther., 87 (3), pp. 272-277
Lanza, V., D’Agata, R., Iacono, G., Bellia, F., Spoto, G., Vecchio, G., Cyclam glycoconjugates as lectin ligands and protective agents of metal-induced amyloid aggregation (2015) J. Inorg. Biochem., 153, pp. 377-382
Lanza, V., Bellia, F., D’Agata, R., Grasso, G., Rizzarelli, E., Vecchio, G., New glycoside derivatives of carnosine and analogs resistant to carnosinase hydrolysis: Synthesis and characterization of their copper(II) complexes (2011) J. Inorg. Biochem., 105 (2), pp. 181-188
Tabbì, G., Magrì, A., Giuffrida, A., Lanza, V., Pappalardo, G., Naletova, I., Nicoletti, V.G., Rizzarelli, E., Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion and protective ability against metal induced cell toxicity (2015) J. Inorg. Biochem., 142, pp. 39-46
Bush, A.I., Tanzi, R.E., Therapeutics for Alzheimer’s disease based on the metal hypothesis (2008) Neurotherapeutics, 5 (3), pp. 421-432
Prachayasittikul, V., Prachayasittikul, S., Ruchirawat, S., Prachayasittikul, V., 8-hydroxyquinolines: A review of their metal chelating properties and medicinal applications (2013) Drug Des. Devel. Ther., 7, pp. 1157-1178
Cherdtrakulkiat, R., Boonpangrak, S., Sinthupoom, N., Prachayasittikul, S., Ruchirawat, S., Prachayasittikul, V., Derivatives (halogen, nitro and amino) of 8-hydroxyquinoline with highly potent antimicrobial and antioxidant activities (2016) Biochem Biophys Rep, 6, pp. 135-141
Kumar, N., Knopman, D.S., SMON, clioquinol, and copper (2005) Postgrad. Med. J., 81 (954), p. 227
Arbiser, J.L., Kraeft, S.K., Van Leeuwen, R., Hurwitz, S.J., Selig, M., Dickersin, G.R., Flint, A., Chen, L.B., Clioquinol-zinc chelate: A candidate causative agent of subacute myelo-optic neuropathy (1998) Mol. Med., 4 (10), pp. 665-670
Mamoli, B., Thaler, A., Heilig, P., Siakos, G., Subacute myelo-optic-neuropathy (S.M.O.N.) following treatment with clioquinol (1975) J. Neurol., 209 (2), pp. 139-147
Chen, D., Cui, Q.C., Yang, H., Barrea, R.A., Sarkar, F.H., Sheng, S., Yan, B., Dou, Q.P., Clioquinol, a therapeutic agent for Alzheimer’s disease, has proteasome-inhibitory, androgen receptor-suppressing, apoptosis-inducing, and antitumor activities in human prostate cancer cells and xenografts (2007) Cancer Res., 67 (4), pp. 1636-1644
Ding, W.-Q., Liu, B., Vaught, J.L., Yamauchi, H., Lind, S.E., Anticancer activity of the antibiotic clioquinol (2005) Cancer Res., 65 (8), pp. 3389-3395
He, M., Luo, M., Liu, Q., Chen, J., Li, K., Zheng, M., Weng, Y., Liu, A., Combination treatment with fasudil and clioquinol produces synergistic anti-tumor effects in U87 glioblastoma cells by activating apoptosis and autophagy (2016) J. Neurooncol., 127 (2), pp. 261-270
Milardi, D., Arnesano, F., Grasso, G., Magrì, A., Tabbì, G., Scintilla, S., Natile, G., Rizzarelli, E., Ubiquitin stability and the Lys63-linked polyubiquitination site are compromised on copper binding (2007) Angew. Chem. Int. Ed. Engl., 46 (42), pp. 7993-7995
Arena, G., Fattorusso, R., Grasso, G., Grasso, G.I., Isernia, C., Malgieri, G., Milardi, D., Rizzarelli, E., Zinc(II) complexes of ubiquitin: Speciation, affinity and binding features (2011) Chemistry, 17 (41), pp. 11596-11603
Santoro, A.M., Monaco, I., Attanasio, F., Lanza, V., Pappalardo, G., Tomasello, M.F., Cunsolo, A., Milardi, D., Copper(II) ions affect the gating dynamics of the 20S proteasome: A molecular and in cell study (2016) Sci. Rep., 6, p. 33444
Mao, X., Schimmer, A.D., The toxicology of clioquinol (2008) Toxicol. Lett., 182 (1-3), pp. 1-6
Arena, G., Bellia, F., Frasca, G., Grasso, G., Lanza, V., Rizzarelli, E., Tabbì, G., Milardi, D., Inorganic stressors of ubiquitin (2013) Inorg. Chem., 52 (16), pp. 9567-9573
Bondiolotti, G., Sala, M., Pollera, C., Gervasoni, M., Puricelli, M., Ponti, W., Bareggi, S.R., Pharmacokinetics and distribution of clioquinol in golden hamsters (2007) J. Pharm. Pharmacol., 59 (3), pp. 387-393
Prati, F., Bergamini, C., Fato, R., Soukup, O., Korabecny, J., Andrisano, V., Bartolini, M., Bolognesi, M.L., Novel 8-hydroxyquinoline derivatives as multitarget compounds for the treatment of Alzheimer’s disease (2016) ChemMedChem, 11 (12), pp. 1284-1295
Kawada, H., Kador, P.F., Orally bioavailable metal chelators and radical scavengers: Multifunctional antioxidants for the coadjutant treatment of neurodegenerative diseases (2015) J. Med. Chem., 58 (22), pp. 8796-8805
Kaur, D., Yantiri, F., Rajagopalan, S., Kumar, J., Mo, J.Q., Boonplueang, R., Viswanath, V., Andersen, J.K., Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: A novel therapy for Parkinson’s disease (2003) Neuron, 37 (6), pp. 899-909
Nguyen, T., Hamby, A., Massa, S.M., Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates pathology in a huntington’s disease mouse model (2005) Proc. Natl. Acad. Sci. USA, 102 (33), pp. 11840-11845
Jones, M.R., Dyrager, C., Hoarau, M., Korshavn, K.J., Lim, M.H., Ramamoorthy, A., Storr, T., Multifunctional quinoline-triazole derivatives as potential modulators of amyloid-β peptide aggregation (2016) J. Inorg. Biochem., 158, pp. 131-138
Oliveri, V., Grasso, G.I., Bellia, F., Attanasio, F., Viale, M., Vecchio, G., Soluble sugar-based quinoline derivatives as new antioxidant modulators of metal-induced amyloid aggregation (2015) Inorg. Chem., 54 (6), pp. 2591-2602
Oliveri, V., Bellia, F., Vecchio, G., Cyclodextrin 3-functionalized with 8-hydroxyquinoline as an antioxidant inhibitor of metal-induced amyloid aggregation (2015) Chem-PlusChem, 80 (4), pp. 762-770
Barnham, K.J., Cappai, R., Beyreuther, K., Masters, C.L., Hill, A.F., Delineating common molecular mechanisms in Alzheimer’s and prion diseases (2006) Trends Biochem. Sci., 31 (8), pp. 465-472
Pollera, C., Lucchini, B., Formentin, E., Bareggi, S., Poli, G., Ponti, W., Evaluation of anti-prionic activity of clioquinol in an in vivo model (Mesocricetus auratus) (2005) Vet. Res. Commun., 29, pp. 253-255
Robert, A., Liu, Y., Nguyen, M., Meunier, B., Regulation of copper and iron homeostasis by metal chelators: A possible chemotherapy for Alzheimer’s disease (2015) Acc. Chem. Res., 48 (5), pp. 1332-1339
Bilder, G.E., (2016) Human Biological Aging: From Macromolecules to Organ Systems, , John Wiley & Sons
Gu, X., Chen, H., Gao, X., Nanotherapeutic strategies for the treatment of Alzheimer’s disease (2015) Ther. Deliv., 6 (2), pp. 177-195
Filiz, G., Price, K.A., Caragounis, A., Du, T., Crouch, P.J., White, A.R., The role of metals in modulating metalloprote-ase activity in the AD brain (2008) Eur. Biophys. J., 37 (3), pp. 315-321
Bush, A.I., Drug development based on the metals hypothesis of Alzheimer’s disease (2008) J. Alzheimers Dis., 15 (2), pp. 223-240
Adlard, P.A., Cherny, R.A., Finkelstein, D.I., Gautier, E., Robb, E., Cortes, M., Volitakis, I., Bush, A.I., Rapid restoration of cognition in Alzheimer’s transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial abeta (2008) Neuron, 59 (1), pp. 43-55
Adlard, P.A., Bica, L., White, A.R., Nurjono, M., Filiz, G., Crouch, P.J., Donnelly, P.S., Bush, A.I., Metal ionophore treatment restores dendritic spine density and synaptic protein levels in a mouse model of Alzheimer’s disease (2011) PLoS One, 6 (3), p. e17669
Crouch, P.J., Savva, M.S., Hung, L.W., Donnelly, P.S., Mot, A.I., Parker, S.J., Greenough, M.A., White, A.R., The Alzheimer’s therapeutic PBT2 promotes amyloid-β degradation and GSK3 phosphorylation via a metal chaperone activity (2011) J. Neurochem., 119 (1), pp. 220-230
Cherny, R.A., Ayton, S., Finkelstein, D.I., Bush, A.I., McColl, G., Massa, S.M., PBT2 reduces toxicity in a c. Ele-gans model of polyQ aggregation and extends lifespan, reduces striatal atrophy and improves motor performance in the r6/2 mouse model of huntington’s disease (2012) J. Hunting-Tons Dis., 1 (2), pp. 211-219
Johanssen, T., Suphantarida, N., Donnelly, P.S., Liu, X.M., Petrou, S., Hill, A.F., Barnham, K.J., PBT2 inhibits glutamate-induced excitotoxicity in neurons through metal-mediated preconditioning (2015) Neurobiol. Dis., 81, pp. 176-185
Safety, tolerability, and efficacy of PBT2 in huntington’s disease:Phase, a. Safety, tolerability, and efficacy of PBT2 in huntington’s disease: A phase 2, randomised, double-blind, placebo-controlled trial (2015) Lancet Neurol., 14 (1), pp. 39-47
Sanz, C.M., Hanaire, H., Vellas, B.J., Sinclair, A.J., Andrieu, S., Diabetes mellitus as a modulator of functional impairment and decline in Alzheimer’s disease. The real.FR cohort (2012) Diabet. Med., 29 (4), pp. 541-548
Stewart, R., Liolitsa, D., Type 2 diabetes mellitus, cognitive impairment and dementia (1999) Diabet. Med., 16 (2), pp. 93-112
Li, L., Hölscher, C., Common pathological processes in Alzheimer disease and type 2 diabetes: A review (2007) Brain Res. Brain Res. Rev., 56 (2), pp. 384-402
Liu, Y., Liu, F., Grundke-Iqbal, I., Iqbal, K., Gong, C.-X., Deficient brain insulin signalling pathway in Alzheimer’s disease and diabetes (2011) J. Pathol., 225 (1), pp. 54-62
Khan, A.R., Awan, F.R., Metals in the pathogenesis of type 2 diabetes (2014) J. Diabetes Metab. Disord., 13 (1), p. 16
Kandimalla, R., Thirumala, V., Reddy, P.H., Is Alzheimer’s disease a type 3 diabetes? a critical appraisal (2017) Biochim. Biophys. Acta, 1863 (5), pp. 1078-1089
Kroner, Z., The relationship between Alzheimer’s disease and diabetes: Type 3 diabetes? (2009) Altern. Med. Rev., 14 (4), pp. 373-379
Yarchoan, M., Arnold, S.E., Repurposing diabetes drugs for brain insulin resistance in Alzheimer disease (2014) Diabetes, 63 (7), pp. 2253-2261
Logie, L., Harthill, J., Patel, K., Bacon, S., Hamilton, D.L., Macrae, K., McDougall, G., Rena, G., Cellular responses to the metal-binding properties of metformin (2012) Diabetes, 61 (6), pp. 1423-1433
Rena, G., Pearson, E.R., Sakamoto, K., Molecular mechanism of action of metformin: Old or new insights? (2013) Diabe-Tologia, 56 (9), pp. 1898-1906
Viollet, B., Guigas, B., Sanz Garcia, N., Leclerc, J., Foretz, M., Andreelli, F., Cellular and molecular mechanisms of metformin: An overview (2012) Clin. Sci., 122 (6), pp. 253-270
Hawley, S.A., Ross, F.A., Chevtzoff, C., Green, K.A., Evans, A., Fogarty, S., Towler, M.C., Hardie, D.G., Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation (2010) Cell Metab., 11 (6), pp. 554-565
Gupta, A., Bisht, B., Dey, C.S., Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer’s-like changes (2011) Neuropharmacology, 60 (6), pp. 910-920
Wang, J., Gallagher, D., DeVito, L.M., Cancino, G.I., Tsui, D., He, L., Keller, G.M., Miller, F.D., Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation (2012) Cell Stem Cell, 11 (1), pp. 23-35
Barini, E., Antico, O., Zhao, Y., Asta, F., Tucci, V., Catelani, T., Marotta, R., Gasparini, L., Metformin promotes tau aggregation and exacerbates abnormal behavior in a mouse model of tauopathy (2016) Mol. Neurodegener., 11, p. 16
Chen, Y., Zhou, K., Wang, R., Liu, Y., Kwak, Y.-D., Ma, T., Thompson, R.C., Liao, F.-F., Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer’s amyloid peptides via up-regulating BACE1 transcription (2009) Proc. Natl. Acad. Sci. USA, 106 (10), pp. 3907-3912
Ray, P., Complex compounds of biguanides and guanylureas with metallic elements (1961) Chem. Rev., 61 (4), pp. 313-359
Doşa, M.D., Hangan, L.-T., Crauciuc, E., Galeş, C., Nechifor, M., Influence of therapy with metformin on the concentration of certain divalent cations in patients with non-insulin-dependent diabetes mellitus (2011) Biol. Trace Elem. Res., 142 (1), pp. 36-46
Repiščák, P., Erhardt, S., Rena, G., Paterson, M.J., Bio-molecular mode of action of metformin in relation to its copper binding properties (2014) Biochemistry, 53 (4), pp. 787-795
Arena, G., Pappalardo, G., Sovago, I., Rizzarelli, E., Copper(II) interaction with amyloid-β: Affinity and speciation (2012) Coord. Chem. Rev., 256 (1-2), pp. 3-12
Grasso, G., Pietropaolo, A., Spoto, G., Pappalardo, G., Tundo, G.R., Ciaccio, C., Coletta, M., Rizzarelli, E., Copper(I) and copper(II) inhibit aβ peptides proteolysis by insulin-degrading enzyme differently: Implications for metallostasis alteration in Alzheimer’s disease (2011) Chemistry, 17 (9), pp. 2752-2762
Martins, M.B., Carvalho, I., Diketopiperazines: Biological activity and synthesis (2007) Tetrahedron, 63 (40), pp. 9923-9932
McCleland, K., Milne, P.J., Lucieto, F.R., Frost, C., Brauns, S.C., Van De Venter, M., Du Plessis, J., Dyason, K., An investigation into the biological activity of the selected histidine-containing diketopiperazines cyclo(His-phe) and cyclo(His-tyr) (2004) J. Pharm. Pharmacol., 56 (9), pp. 1143-1153
Jain, H.D., Zhang, C., Zhou, S., Zhou, H., Ma, J., Liu, X., Liao, X., Cook, J.M., Synthesis and structure-activity relationship studies on tryprostatin a, an inhibitor of breast cancer resistance protein (2008) Bioorg. Med. Chem., 16 (8), pp. 4626-4651
Sanz-Cervera, J.F., Stocking, E.M., Usui, T., Osada, H., Williams, R.M., Synthesis and evaluation of microtubule assembly inhibition and cytotoxicity of prenylated derivatives of cyclo-L-trp-L-pro (2000) Bioorg. Med. Chem., 8 (10), pp. 2407-2415
Borthwick, A.D., 2,5-diketopiperazines: Synthesis, reactions, medicinal chemistry, and bioactive natural products (2012) Chem. Rev., 112 (7), pp. 3641-3716
Daugan, A., Grondin, P., Ruault, C., Le Monnier De Gouville, A.-C., Coste, H., Linget, J.M., Kirilovsky, J., Labaudinière, R., The discovery of tadalafil: A novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dione analogues (2003) J. Med. Chem., 46 (21), pp. 4533-4542
Borthwick, A.D., Liddle, J., The design of orally bioavailable 2, 5-diketopiperazine oxytocin antagonists: From concept to clinical candidate for premature labor (2011) Med. Res. Rev., 31 (4), pp. 576-604
Nicholson, B., Lloyd, G.K., Miller, B.R., Palladino, M.A., Kiso, Y., Hayashi, Y., Neuteboom, S.T., NPI-2358 is a tu-bulin-depolymerizing agent: In-vitro evidence for activity as a tumor vascular-disrupting agent (2006) Anticancer Drugs, 17 (1), pp. 25-31
Maeda, K., Mitsuya, H., Development of therapeutics for AIDS: Structure-based molecular targeting (2007) Tuberculosis (Edinb.), 87, pp. S31-S34
Miyamura, S., Ogasawara, N., Otsuka, H., Niwayama, S., Tanaka, H., Antibiotic no. 5879, a new water-soluble antibiotic against gram-negative bacteria (1972) J. Antibiot., 25 (10), pp. 610-612
Teixidó, M., Zurita, E., Malakoutikhah, M., Tarragó, T., Giralt, E., Diketopiperazines as a tool for the study of transport across the blood-brain barrier (BBB) and their potential use as BBB-shuttles (2007) J. Am. Chem. Soc., 129 (38), pp. 11802-11813
Bellezza, I., Peirce, M.J., Minelli, A., Cyclic dipeptides: From bugs to brain (2014) Trends Mol. Med., 20 (10), pp. 551-558
Cornacchia, C., Cacciatore, I., Baldassarre, L., Mollica, A., Feliciani, F., Pinnen, F., 2,5-diketopiperazines as neuroprotective agents (2012) Mini Rev. Med. Chem., 12 (1), pp. 2-12
Adlard, P.A., Bush, A.I., Metals and Alzheimer’s disease (2006) J. Alzheimers Dis., 10 (2-3), pp. 145-163
Arena, G., Impellizzeri, G., Maccarrone, G., Pappalardo, G., Rizzarelli, E., Co-ordination properties of cyclopeptides. Formation and stability of zinc(II) and copper(II) complexes of histidine-containing cyclopeptides, or imidazole (1994) J. Chem. Soc., Dalton Trans., pp. 1227-1230
Arena, G., Bonomo, R.P., Impellizzeri, G., Izatt, R.M., Lamb, J.D., Rizzarelli, E., Coordination properties of cyclopeptides. Formation, stability, and structure of proton and copper(II) complexes of cyclo-(l-histidyl-l-histidyl) in aqueous solution (1987) Inorg. Chem., 26 (6), pp. 795-800
Czapor, H., Bielińska, S., Kamysz, W., Szyrwiel, Ł., Brasuń, J., The cyclopeptides with the multi-his motif as ligands for copper(II) (2011) J. Inorg. Biochem., 105 (2), pp. 297-302
Walter, R., Hoffman, P.L., Flexner, J.B., Flexner, L.B., Neurohypophyseal hormones, analogs, and fragments: Their effect on puromycin-induced amnesia (1975) Proc. Natl. Acad. Sci. USA, 72 (10), pp. 4180-4184
Repurposing of Copper(II)-chelating Drugs for the Treatment of Neurodegenerative Diseases