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 β-protein (Aβ) in studies done in vitro and in vivo. Moreover, various antioxidants have been reported to inhibit the formation and extension of β-amyloid fibrils (fAβ), as well as to destabilize preformed fAβ in vitro. In cell culture experiments, destabilized fAβ were suggested to be less toxic than intact fAβ. In transgenic mice model studies, some antioxidant coumpounds reduced plaque burden in vivo. In this article, we review the recent advances in the research on the antioxidants that inhibit the formation of fAβ, as well as destabilize preformed fAβ. Although the mechanisms by which these compounds inhibit fAβ formation from Aβ, and destabilize preformed fAβ are still unclear, they could be key molecules for the development of preventives and therapeutics for AD.