title: Vitamin A has anti-oligomerization effects on amyloid-β in vitro.
abstract: Inhibition of amyloid-β (Aβ) aggregation is an attractive therapeutic strategy for treatment of Alzheimer's disease (AD). We previously reported that vitamin A and β-carotene inhibit fibrillation of Aβ40 and Aβ42 (Ono et al, 2004, Exp Neurol). In this study, we firstly examined the effects of vitamin A (retinoic acid, retinol, and retinal), β-carotene, vitamin B2, vitamin B6, vitamin C, vitamin E, coenzyme Q10, and α-lipoic acid on oligomerization of Aβ40 and Aβ42 in vitro; vitamin A and β-carotene dose-dependently inhibited oligomerization of Aβ40 and Aβ42. Furthermore, retinoic acid decreased cellular toxicity by inhibition of Aβ42 oligomerization. Second, we analyzed how vitamin A inhibits Aβ aggregation by using fluorescence spectroscopy and thioflavin T assay with two Aβ fragments, Aβ1-16 and Aβ25-35. A fluorescence peak of retinoic acid was greatly restrained in the presence of Aβ25-35, and retinoic acid inhibited aggregation of Aβ25-35, but not of Aβ1-16, which suggest the specific binding of retinoic acid to the C-terminal portion of Aβ. Thus, vitamin A and β-carotene might be key molecules for prevention of AD.
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Takasaki
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yoshiike
authors.forename: Mie
authors.initials: M
authors.lastname: Hirohata
authors.forename: Tokuhei
authors.initials: T
authors.lastname: Ikeda
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Morinaga
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takashima
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D001704:Biopolymers / Q000037:antagonists & inhibitors / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014801:Vitamin A / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D001704:Biopolymers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D014801:Vitamin A