title: Resveratrol inhibits beta-amyloid oligomeric cytotoxicity but does not prevent oligomer formation.
abstract: Beta-amyloid (Abeta) aggregation has been strongly associated with the neurodegenerative pathology and a cascade of harmful event rated to Alzheimer's disease (AD). Inhibition of Abeta assembly, destabilization of preformed Abeta aggregates and attenuation of the cytotoxicity of Abeta oligomers and fibrils could be valuable therapeutics of patients with AD. Recent studies suggested that moderate consumption of red wine and intake of dietary polyphenols, such as resveratrol, may benefit AD phenotypes in animal models and reduce the relative risk for AD clinical dementia. To understand the mechanism of this neuroprotection, we studied the effects of resveratrol, an active ingredient of polyphenols in wine and many plants, on the polymerization of Abeta42 monomer, the destabilization of Abeta42 fibril and the cell toxicity of Abeta42 in vitro using fluorescence spectroscopic analysis with thioflavin T (ThT), transmission electron microscope (TEM), circular dichroism (CD) and MTT assay. The results showed that resveratrol could dose-dependently inhibit Abeta42 fibril formation and cytotoxicity but could not prevent Abeta42 oligomerization. The studies by Western-blot, dot-blot and ELISA confirmed that the addition of resveratrol resulted in numerous Abeta42 oligomer formation. In conjunction with the concept that Abeta oligomers are linked to Abeta toxicity, we speculate that aside from potential antioxidant activities, resveratrol may directly bind to Abeta42, interfere in Abeta42 aggregation, change the Abeta42 oligomer conformation and attenuate Abeta42 oligomeric cytotoxicity.
authors.affiliation: Tsinghua University School of Medicine, Haidian District, Beijing 100084, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Wang
authors.forename: Shi-gao
authors.initials: SG
authors.lastname: Yang
authors.forename: Yu-jiong
authors.initials: YJ
authors.lastname: Wang
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Xue-ting
authors.initials: XT
authors.lastname: Du
authors.forename: Xiao-xia
authors.initials: XX
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.forename: Rui-tian
authors.initials: RT
authors.lastname: Liu
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism* / Q000633:toxicity / Q000648:ultrastructure; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D052160:Benzothiazoles; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism / Q000379:methods; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008968:Molecular Conformation; D015394:Molecular Structure; D009447:Neuroblastoma / Q000473:pathology; D010446:Peptide Fragments / Q000633:toxicity; D020836:Protein Structure, Quaternary; D000077185:Resveratrol; D013050:Spectrometry, Fluorescence / Q000379:methods; D013267:Stilbenes / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D052160:Benzothiazoles; D010446:Peptide Fragments; D013267:Stilbenes; D013778:Tetrazolium Salts; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); C009462:thioflavin T; C022616:thiazolyl blue; D000077185:Resveratrol