Alpha-lipoic acid exhibits anti-amyloidogenicity for beta-amyloid fibrils in vitro.
Inhibition of the formation of beta-amyloid fibrils (fAbeta), as well as the destabilization of preformed fAbeta in the CNS would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of alpha-lipoic acid (LA) and the metabolic product of LA, dihydrolipoic acid (DHLA), on the formation, extension, and destabilization of fAbeta at pH 7.5 at 37 degrees C in vitro. LA and DHLA dose-dependently inhibited fAbeta formation from amyloid beta-protein, as well as their extension. Moreover, they destabilized preformed fAbetas. LA and DHLA could be key molecules for the development of therapeutics for AD.
Ono
Kenjiro
K
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Hirohata
Mie
M
Yamada
Masahito
M
D000682:Amyloid / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure*; D052160:Benzothiazoles; D009637:Masoprocol / Q000494:pharmacology; D008854:Microscopy, Electron; D012293:Rifampin / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013752:Tetracycline / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D008063:Thioctic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D013844:Thiazoles; C009462:thioflavin T; D008063:Thioctic Acid; D009637:Masoprocol; C015144:dihydrolipoic acid; D013752:Tetracycline; D012293:Rifampin