Vitamin A potently destabilizes preformed α-synuclein fibrils in vitro:: Implications for Lewy body diseases

Alpha-synuclein (alpha S) 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 alpha S fibrils (f alpha S) and on preformed f alpha S. Among them, vitamin A, beta-carotene and coenzyme Q10 dose-dependently inhibited the formation of f alpha S. Moreover, they also dose-dependently destabilized preformed f alpha S. 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. (c) 2006 Elsevier Inc. All rights reserved.