Vitamin A potently destabilizes preformed alpha-synuclein fibrils in vitro: implications for Lewy body diseases.
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.
Ono
Kenjiro
K
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Yamada
Masahito
M
D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D052160:Benzothiazoles; D003067:Coenzymes; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009454:Neurofibrils / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism*; D013844:Thiazoles; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D014801:Vitamin A / Q000737:chemistry* / Q000494:pharmacology; D014815:Vitamins / Q000737:chemistry / Q000494:pharmacology; D051844:alpha-Synuclein / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D019207:beta Carotene / Q000737:chemistry / Q000494:pharmacology
D000975:Antioxidants; D052160:Benzothiazoles; D003067:Coenzymes; D018696:Neuroprotective Agents; D013844:Thiazoles; D014815:Vitamins; D051844:alpha-Synuclein; D019207:beta Carotene; D014801:Vitamin A; D014451:Ubiquinone; C009462:thioflavin T; C024989:coenzyme Q10