The development of preventives and therapeutics for Alzheimer's disease that inhibit the formation of β-amyloid fibrils (fAβ), as well as destabilize preformed fAβ

Neuritic plaques composed mainly of amyloid beta-protein (AD) in the brain are an early and invariant neuropathological feature of Alzheimer's disease (AD). The current search for anti-AD drugs is mainly focused on modification of the process of AD deposition in the brain. In this article, the recent development of the molecules that inhibit the formation of beta-amyloid fibrils (fA beta), as well as destabilize preformed fA beta is reviewed. Recently, various compounds such as curcumin, nicotine and wine-related polyphenols have been reported to inhibit the formation, extension of fA beta, as well as destabilize preformed fA beta at pH 7.5 at 37 degrees C in vitro. In cell culture experiments, destabilized fA beta were suggested to be less toxic than intact fA beta. In transgenic mice model study, some coumpounds such as curcumin and nicotine have also been reported to reduce plaque burden in vivo. Although the mechanisms by which these compounds inhibit fA beta formation from AD, and destabilize preformed fA beta are still unclear, they could be key molecules for the development of preventives and therapeutics for AD.