Document Detail


Vitamin A potently destabilizes preformed alpha-synuclein fibrils in vitro: implications for Lewy body diseases.
MedLine Citation:
PMID:  17169566     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Alpha-synuclein (alphaS) is the major component of the filamentous inclusions that constitute defining characteristics of Lewy body diseases (LBD) and multiple system atrophy (MSA). Clinically, antioxidant vitamins, such as vitamin E and the vitamin-like substance coenzyme Q10, have been used in the treatment of LBD with some efficacy. Using fluorescence spectroscopy with thioflavin S, electron microscopy and atomic force microscopy, here we examined the effects of ten antioxidant vitamins and vitamin-like substances, vitamin A (retinol, retinal and retinoic acid), beta-carotene, vitamins B2, B6, C, E, coenzyme Q10 and alpha-lipoic acid, on the formation of alphaS fibrils (falphaS) and on preformed falphaS. Among them, vitamin A, beta-carotene and coenzyme Q10 dose-dependently inhibited the formation of falphaS. Moreover, they also dose-dependently destabilized preformed falphaS. With such potent anti-fibrillogenic as well as fibril-destabilizing activities, these compounds could be useful in the treatment and prevention of LBD and MSA.
Authors:
Kenjiro Ono; Masahito Yamada
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-12-12
Journal Detail:
Title:  Neurobiology of disease     Volume:  25     ISSN:  0969-9961     ISO Abbreviation:  Neurobiol. Dis.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-26     Completed Date:  2007-04-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9500169     Medline TA:  Neurobiol Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  446-54     Citation Subset:  IM    
Affiliation:
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antioxidants / chemistry,  pharmacology
Coenzymes
Humans
Lewy Body Disease / metabolism*
Microscopy, Atomic Force
Microscopy, Electron
Microscopy, Fluorescence
Neurofibrils / drug effects*,  metabolism,  ultrastructure
Neuroprotective Agents / chemistry*,  pharmacology
Parkinson Disease / metabolism*
Thiazoles
Ubiquinone / analogs & derivatives,  chemistry,  pharmacology
Vitamin A / chemistry*,  pharmacology
Vitamins / chemistry,  pharmacology
alpha-Synuclein / chemistry,  drug effects*,  metabolism
beta Carotene / chemistry,  pharmacology
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Coenzymes; 0/Neuroprotective Agents; 0/Thiazoles; 0/Vitamins; 0/alpha-Synuclein; 11103-57-4/Vitamin A; 1339-63-5/Ubiquinone; 2390-54-7/thioflavin T; 303-98-0/coenzyme Q10; 7235-40-7/beta Carotene

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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