Anti-amyloidogenic effects of antioxidants: implications for the prevention and therapeutics of Alzheimer's disease.
Alzheimer's disease (AD) is one of the most common dementing disorders and has profound medical and social consequences. The initiating molecular event is unknown, and its pathophysiology is highly complex. However, free radical injury appears to be a fundamental process contributing to the neuronal death seen in this disorder, and many studies using surrogate markers of oxidative damage have provided evidence supporting this hypothesis. Various compounds with antioxidant ability attenuated the oxidative stress induced by amyloid beta-protein (Abeta) in studies done in vitro and in vivo. Moreover, various antioxidants have been reported to inhibit the formation and extension of beta-amyloid fibrils (fAbeta), as well as to destabilize preformed fAbeta in vitro. In cell culture experiments, destabilized fAbeta were suggested to be less toxic than intact fAbeta. In transgenic mice model studies, some antioxidant compounds reduced plaque burden in vivo. In this article, we review the recent advances in the research on the antioxidants that inhibit the formation of fAbeta, as well as destabilize preformed fAbeta. Although the mechanisms by which these compounds inhibit fAbeta formation from Abeta, and destabilize preformed fAbeta are still unclear, they could be key molecules for the development of preventives and therapeutics for AD.
Ono
Kenjiro
K
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Hamaguchi
Tsuyoshi
T
Naiki
Hironobu
H
Yamada
Masahito
M
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D020836:Protein Structure, Quaternary
D016229:Amyloid beta-Peptides; D000975:Antioxidants