The development of preventives and therapeutics for Alzheimer's disease that inhibit the formation of beta-amyloid fibrils (fAbeta), as well as destabilize preformed fAbeta.
Neuritic plaques composed mainly of amyloid beta-protein (Abeta) 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 Abeta deposition in the brain. In this article, the recent development of the molecules that inhibit the formation of beta-amyloid fibrils (fAbeta), as well as destabilize preformed fAbeta is reviewed. Recently, various compounds such as curcumin, nicotine and wine-related polyphenols have been reported to inhibit the formation, extension of fAbeta, as well as destabilize preformed fAbeta at pH 7.5 at 37 degrees C in vitro. In cell culture experiments, destabilized fAbeta were suggested to be less toxic than intact fAbeta. 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 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 & Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Naiki
Hironobu
H
Yamada
Masahito
M
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011487:Protein Conformation / Q000187:drug effects
D016229:Amyloid beta-Peptides