Vitamin A exhibits potent antiamyloidogenic and fibril-destabilizing effects in vitro.
Cerebral deposition of amyloid beta-peptide (Abeta) in the brain is an invariant feature of Alzheimer disease (AD). Plasma or cerebrospinal fluid concentrations of antioxidant vitamins and carotenoids, such as vitamins A, C, E, and beta-carotene, have been reported to be lower in AD patients, and these vitamins clinically have been demonstrated to slow the progression of dementia. In this study, we used fluorescence spectroscopy with thioflavin T (ThT) and electron microscopy to examine the effects of vitamin A (retinol, retinal, and retinoic acid), beta-carotene, and vitamins B2, B6, C, and E on the formation, extension, and destabilization of beta-amyloid fibrils (fAbeta) in vitro. Among them, vitamin A and beta-carotene dose-dependently inhibited formation of fAbeta from fresh Abeta, as well as their extension. Moreover, they dose-dependently destabilized preformed fAbetas. The overall activity of the molecules examined was in the order of retinol = retinal > beta-carotene > retinoic acid. Although the exact mechanisms are still unclear, vitamins A and beta-carotene could be key molecules for the prevention and therapy of AD.
Ono
Kenjiro
K
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Yoshiike
Yuji
Y
Takashima
Akihiko
A
Hasegawa
Kazuhiro
K
Naiki
Hironobu
H
Yamada
Masahito
M
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000975:Antioxidants / Q000494:pharmacology; D052160:Benzothiazoles; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008854:Microscopy, Electron; D015394:Molecular Structure; D009454:Neurofibrils / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D012172:Retinaldehyde / Q000494:pharmacology; D013844:Thiazoles; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*; D019207:beta Carotene / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D052160:Benzothiazoles; D013844:Thiazoles; D014815:Vitamins; D019207:beta Carotene; D014801:Vitamin A; C009462:thioflavin T; D014212:Tretinoin; D012172:Retinaldehyde