Document Detail


Antioxidant compounds have potent anti-fibrillogenic and fibril-destabilizing effects for alpha-synuclein fibrils in vitro.
MedLine Citation:
PMID:  16524383     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aggregation of alpha-synuclein (alphaS) in the brain has been implicated as a critical step in the development of Lewy body diseases (LBD) and multiple system atrophy (MSA). Various antioxidants not only inhibit the formation of beta-amyloid fibrils (fAbeta), but also destabilize preformed fAb in vitro. Using fluorescence spectroscopy with thioflavin S and electron microscopy, here we examined the effects of the antioxidants nordihydroguaiaretic acid, curcumin, rosmarinic acid, ferulic acid, wine-related polyphenols [tannic acid, myricetin, kaempferol (+)-catechin and (-)-epicatechin], docosahexaenoic acid, eicosapentaenoic acid, rifampicin and tetracycline on the formation of alphaS fibrils (falphaS) and on preformed falphaS. All molecules, except for docosahexaenoic acid and eicosapentaenoic acid, dose-dependently inhibited the formation of falphaS. Moreover, these molecules dose-dependently destabilized preformed falphaS. The overall activity of the molecules examined was in the order of: tannic acid=nordihydroguaiaretic acid=curcumin=rosmarinic acid=myricetin>kaempferol=ferulic acid>(+)-catechin=(-)-epicatechin>rifampicin=tetracycline. These compounds with anti-fibrillogenic as well as antioxidant activities could be key molecules for the development of preventives and therapeutics for LBD and MSA as well as Alzheimer's disease.
Authors:
Kenjiro Ono; Masahito Yamada
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-08
Journal Detail:
Title:  Journal of neurochemistry     Volume:  97     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-16     Completed Date:  2006-05-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  105-15     Citation Subset:  IM    
Affiliation:
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
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MeSH Terms
Descriptor/Qualifier:
Aged
Antioxidants / chemistry*,  pharmacology
Cerebrospinal Fluid / chemistry*
Dose-Response Relationship, Drug
Female
Humans
Lewy Body Disease / cerebrospinal fluid*
Male
Microscopy, Electron, Transmission
Molecular Structure
Neurofibrillary Tangles / chemistry*,  drug effects,  ultrastructure
Plant Extracts / chemistry,  pharmacology
Spectrometry, Fluorescence
alpha-Synuclein / chemistry*,  drug effects,  metabolism
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Plant Extracts; 0/alpha-Synuclein

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