Identification of 5-Methoxyflavone as a Novel DNA Polymerase-Beta Inhibitor and Neuroprotective Agent against Beta-Amyloid Toxicity (381 views)
J Nat Prod (ISSN: 0163-3864), 2015; 78(11): 2704-2711.
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Paper type: Journal Article,
Impact factor: 3.662, 5-year impact factor: 3.644
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84948823181&doi=10.1021%2facs.jnatprod.5b00621&partnerID=40&md5=5888f4cb204268bac659d6e8042fab6f
Keywords: 5 Methoxyflavone, Amyloid Beta Protein[1-42], Cyclin A2, Dna Directed Dna Polymerase Beta, Flavone Derivative, Neuroprotective Agent, Nucleotidyltransferase Inhibitor, Oleanolic Acid, Unclassified Drug, Zalcitabine, 5-Methoxyflavone, Enzyme Inhibitor, Apoptosis, Article, Cell Cycle G2 Phase, Cell Cycle Progression, Cell Cycle S Phase, Cell Viability, Conformational Transition, Controlled Study, Dna Replication, Embryo, Enzyme Inhibition, Human, Human Cell, Hydrogen Bond, Hydrophobicity, In Vitro Study, Molecular Docking, Mouse, Nerve Cell Culture, Nerve Cell Necrosis, Nonhuman, Protein Expression, Alzheimer Disease, Antagonists And Inhibitors, Cell Death, Cell Division, Chemical Structure, Chemistry, Drug Effects, Metabolism, Parkinson Disease, Pathology, Molecular Structure,
Affiliations:
*** IBB - CNR ***
Department of Biomedical and Biotechnological Sciences, Catania, Italy
Department of Drug Sciences, University of Catania, Catania, Italy
Institute of Biostructure and Bioimaging, National Research Council (CNR), Catania, Italy
References:
Not available.
J Nat Prod (ISSN: 0163-3864), 2015; 78(11): 2704-2711.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 3.662, 5-year impact factor: 3.644
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84948823181&doi=10.1021%2facs.jnatprod.5b00621&partnerID=40&md5=5888f4cb204268bac659d6e8042fab6f
Keywords: 5 Methoxyflavone, Amyloid Beta Protein[1-42], Cyclin A2, Dna Directed Dna Polymerase Beta, Flavone Derivative, Neuroprotective Agent, Nucleotidyltransferase Inhibitor, Oleanolic Acid, Unclassified Drug, Zalcitabine, 5-Methoxyflavone, Enzyme Inhibitor, Apoptosis, Article, Cell Cycle G2 Phase, Cell Cycle Progression, Cell Cycle S Phase, Cell Viability, Conformational Transition, Controlled Study, Dna Replication, Embryo, Enzyme Inhibition, Human, Human Cell, Hydrogen Bond, Hydrophobicity, In Vitro Study, Molecular Docking, Mouse, Nerve Cell Culture, Nerve Cell Necrosis, Nonhuman, Protein Expression, Alzheimer Disease, Antagonists And Inhibitors, Cell Death, Cell Division, Chemical Structure, Chemistry, Drug Effects, Metabolism, Parkinson Disease, Pathology, Molecular Structure,
Affiliations:
*** IBB - CNR ***
Department of Biomedical and Biotechnological Sciences, Catania, Italy
Department of Drug Sciences, University of Catania, Catania, Italy
Institute of Biostructure and Bioimaging, National Research Council (CNR), Catania, Italy
References:
Not available.
Identification of 5-Methoxyflavone as a Novel DNA Polymerase-Beta Inhibitor and Neuroprotective Agent against Beta-Amyloid Toxicity
Cell-cycle reactivation is a core feature of degenerating neurons in Alzheimer's disease (AD) and Parkinson's disease (PD). A variety of stressors, including β-amyloid (Aβ) in the case of AD, can force neurons to leave quiescence and to initiate an ectopic DNA replication process, leading to neuronal death rather than division. As the primary polymerase (pol) involved in neuronal DNA replication, DNA pol-β contributes to neuronal death, and DNA pol-β inhibitors may prove to be effective neuroprotective agents. Currently, specific and highly active DNA pol-β inhibitors are lacking. Nine putative DNA pol-β inhibitors were identified in silico by querying the ZINC database, containing more than 35 million purchasable compounds. Following pharmacological evaluation, only 5-methoxyflavone (1) was validated as an inhibitor of DNA pol-β activity. Cultured primary neurons are a useful model to investigate the neuroprotective effects of potential DNA pol-β inhibitors, since these neurons undergo DNA replication and death when treated with Aβ. Consistent with the inhibition of DNA pol-β, 5-methoxyflavone (1) reduced the number of S-phase neurons and the ensuing apoptotic death triggered by Aβ. 5-Methoxyflavone (1) is the first flavonoid compound able to halt neurodegeneration via a definite molecular mechanism rather than through general antioxidant and anti-inflammatory properties. © 2015 The American Chemical Society and American Society of Pharmacognosy.
Cell-cycle reactivation is a core feature of degenerating neurons in Alzheimer's disease (AD) and Parkinson's disease (PD). A variety of stressors, including β-amyloid (Aβ) in the case of AD, can force neurons to leave quiescence and to initiate an ectopic DNA replication process, leading to neuronal death rather than division. As the primary polymerase (pol) involved in neuronal DNA replication, DNA pol-β contributes to neuronal death, and DNA pol-β inhibitors may prove to be effective neuroprotective agents. Currently, specific and highly active DNA pol-β inhibitors are lacking. Nine putative DNA pol-β inhibitors were identified in silico by querying the ZINC database, containing more than 35 million purchasable compounds. Following pharmacological evaluation, only 5-methoxyflavone (1) was validated as an inhibitor of DNA pol-β activity. Cultured primary neurons are a useful model to investigate the neuroprotective effects of potential DNA pol-β inhibitors, since these neurons undergo DNA replication and death when treated with Aβ. Consistent with the inhibition of DNA pol-β, 5-methoxyflavone (1) reduced the number of S-phase neurons and the ensuing apoptotic death triggered by Aβ. 5-Methoxyflavone (1) is the first flavonoid compound able to halt neurodegeneration via a definite molecular mechanism rather than through general antioxidant and anti-inflammatory properties. © 2015 The American Chemical Society and American Society of Pharmacognosy.
Identification of 5-Methoxyflavone as a Novel DNA Polymerase-Beta Inhibitor and Neuroprotective Agent against Beta-Amyloid Toxicity
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Identification of 5-Methoxyflavone as a Novel DNA Polymerase-Beta Inhibitor and Neuroprotective Agent against Beta-Amyloid Toxicity
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Neurobiology Of Disease (ISSN: 0969-9961), 2008 May; 30(2): 234-242.
Impact Factor: 4.852
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Copani A, Guccione S, Giurato L, Caraci F, Calafiore M, Sortino MA
* The cell cycle molecules behind neurodegeneration in Alzheimer's disease: Perspectives for drug development (546 views)
Curr Med Chem (ISSN: 0929-8673, 1875-533x, 1875-533xelectronic), 2008; 15(24): 2420-2432.
Impact Factor: 4.823
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Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Stella AM
* Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity (1221 views)
Nature Reviews Neuroscience (ISSN: 1471-0048), 2007 Oct; 8(10): 766-775.
Impact Factor: 24.52
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Copani A, Caraci F, Hoozemans J, Calafiore M, Sortino M, Nicoletti F
* The nature of the cell cycle in neurons: Focus on a "non-canonical" pathway of DNA replication causally related to death (721 views)
Bba-Gen Subjects (ISSN: 0925-4439, 0006-3002, 1570-9639), 2007 Apr; 1772(4): 409-412.
Impact Factor: 3.078
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Copani A, Hoozemans JJM, Caraci F, Calafiore M, Van Haastert ES, Veerhuis R, Rozemuller AJM, Aronica E, Sortino MA, Nicoletti F
* Dna Polymerase-Beta Is Expressed Early In Neurons Of Alzheimer'S Disease Brain And Is Loaded Into Dna Replication Forks In Neurons Challenged With Beta-Amyloid (654 views)
J Neurosci (ISSN: 0270-6474, 0361-803x, 1529-2401), 2006; 26(43): 10949-10957.
Impact Factor: 2.117
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Calafiore M, Battaglia G, Zappal A, Trovato-Salinaro E, Caraci F, Caruso M, Vancheri C, Sortino MA, Nicoletti F, Copani A
* Progenitor cells from the adult mouse brain acquire a neuronal phenotype in response to β-amyloid (876 views)
Neurobiol Aging (ISSN: 0197-4580, 1558-1497electronic, 0197-4580linking), 2006; 27(4): 606-613.
Impact Factor: 5.599
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Marrazzo A, Caraci F, Salinaro ET, Su TP, Copani A, Ronsisvalle G
* Neuroprotective effects of sigma-1 receptor agonists against beta-amyloid-induced toxicity (700 views)
Neuroreport (ISSN: 0959-4965), 2005 Sep 1; 16(11): 1223-1226.
Impact Factor: 1.995
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Calabrese V, Colombrita C, Guagliano E, Sapienza M, Ravagna A, Cardile V, Scapagnini G, Santoro AM, Mangiameli A, Butterfield DA, Giuffrida Stella AM, Rizzarelli E
* Protective effect of carnosine during nitrosative stress in astroglial cell cultures (886 views)
Neurochemical Research (ISSN: 0364-3190, 1573-6903), 2005 Jun; 30(6-7): 797-807.
Impact Factor: 2.187
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Filippo C, Mariangela C, Giuseppina F, Pier Luigi C, Angelo B, Marco C, Giuseppe B, Paolo B, Ferdinando N, Agata C, Maria Angela S
* Nicergoline, a drug used for age-dependent cognitive impairment, protects cultured neurons against β-amyloid toxicity (909 views)
Brain Res (ISSN: 0006-8993), 2005; 1047(1): 30-37.
Impact Factor: 2.296
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Wiesehan K, Buder K, Linke RP, Patt S, Stoldt M, Unger E, Schmitt B, Bucci E, Willbold D
* Selection of D-amino-acid peptides that bind to Alzheimer's disease amyloid peptide Aβ1-42 by mirror image phage display (880 views)
Chembiochem (ISSN: 1439-4227, 1439-7633, 1439-7633electronic), 2003; 4(8): 748-753.
Impact Factor: 3.992
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29 Records (29 excluding Abstracts).
Total impact factor: 128.666 (128.666 excluding Abstracts).
Total 5 year impact factor: 124.465 (124.465 excluding Abstracts).
Total impact factor: 128.666 (128.666 excluding Abstracts).
Total 5 year impact factor: 124.465 (124.465 excluding Abstracts).
381 views. Last view on Thursday 12 September 2024, 4:00:29
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