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

Alpha-synuclein (αS) 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 tre...

Full description

Bibliographic Details
Main Authors: Kenjiro Ono, Masahito Yamada
Format: Article
Language:English
Published: Elsevier 2007-02-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996106002737
_version_ 1818414513273176064
author Kenjiro Ono
Masahito Yamada
author_facet Kenjiro Ono
Masahito Yamada
author_sort Kenjiro Ono
collection DOAJ
description Alpha-synuclein (αS) 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), β-carotene, vitamins B2, B6, C, E, coenzyme Q10 and α-lipoic acid, on the formation of αS fibrils (fαS) and on preformed fαS. Among them, vitamin A, β-carotene and coenzyme Q10 dose-dependently inhibited the formation of fαS. Moreover, they also dose-dependently destabilized preformed fαS. 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.
first_indexed 2024-12-14T11:20:17Z
format Article
id doaj.art-9c4650891a884fca8848d934c71b84ea
institution Directory Open Access Journal
issn 1095-953X
language English
last_indexed 2024-12-14T11:20:17Z
publishDate 2007-02-01
publisher Elsevier
record_format Article
series Neurobiology of Disease
spelling doaj.art-9c4650891a884fca8848d934c71b84ea2022-12-21T23:03:46ZengElsevierNeurobiology of Disease1095-953X2007-02-01252446454Vitamin A potently destabilizes preformed α-synuclein fibrils in vitro: Implications for Lewy body diseasesKenjiro Ono0Masahito Yamada1Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, JapanCorresponding author. Fax: +81 76 234 4253.; Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, JapanAlpha-synuclein (αS) 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), β-carotene, vitamins B2, B6, C, E, coenzyme Q10 and α-lipoic acid, on the formation of αS fibrils (fαS) and on preformed fαS. Among them, vitamin A, β-carotene and coenzyme Q10 dose-dependently inhibited the formation of fαS. Moreover, they also dose-dependently destabilized preformed fαS. 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.http://www.sciencedirect.com/science/article/pii/S0969996106002737Vitamin AElectron microscopyAtomic force microscopyLewy body diseasesα-Synuclein fibrilsThioflavin S
spellingShingle Kenjiro Ono
Masahito Yamada
Vitamin A potently destabilizes preformed α-synuclein fibrils in vitro: Implications for Lewy body diseases
Neurobiology of Disease
Vitamin A
Electron microscopy
Atomic force microscopy
Lewy body diseases
α-Synuclein fibrils
Thioflavin S
title Vitamin A potently destabilizes preformed α-synuclein fibrils in vitro: Implications for Lewy body diseases
title_full Vitamin A potently destabilizes preformed α-synuclein fibrils in vitro: Implications for Lewy body diseases
title_fullStr Vitamin A potently destabilizes preformed α-synuclein fibrils in vitro: Implications for Lewy body diseases
title_full_unstemmed Vitamin A potently destabilizes preformed α-synuclein fibrils in vitro: Implications for Lewy body diseases
title_short Vitamin A potently destabilizes preformed α-synuclein fibrils in vitro: Implications for Lewy body diseases
title_sort vitamin a potently destabilizes preformed α synuclein fibrils in vitro implications for lewy body diseases
topic Vitamin A
Electron microscopy
Atomic force microscopy
Lewy body diseases
α-Synuclein fibrils
Thioflavin S
url http://www.sciencedirect.com/science/article/pii/S0969996106002737
work_keys_str_mv AT kenjiroono vitaminapotentlydestabilizespreformedasynucleinfibrilsinvitroimplicationsforlewybodydiseases
AT masahitoyamada vitaminapotentlydestabilizespreformedasynucleinfibrilsinvitroimplicationsforlewybodydiseases