Novel modulators of amyloid-β precursor protein processing21.pdfVIP

Journal of Neurochemistry, 2007, 100, 314–323 doi:10.1111/j.1471-4159.2006.04215.x MINI-REVIEW Novel modulators of amyloid- b precursor protein processing Bor Luen Tang* and Yih Cherng Liou *Department of Biochemistry, Yong Loo Lin School of Medicine and Department of Biological Sciences, National University of Singapore, Singapore Abstract Nogo-B interact with the b-secretase BACE1. Phosphorylated Proteolytic processing of the amyloid precursor protein APP is a Pin1 substrate, which binds to its phosphor-Thr668- (APP) is modulated by the action of enzymes a-, b- and Pro motif. These interactions by and large resulted in a c-secretases, with the latter two mediating the amyloidogenic reduction of Ab generation both in vitro and in vivo. Inhibition production of amyloid-b (Ab). Cellular modulators of APP of Rho and Rho-kinase (ROCK) activity may underlie the processing are well known from studies of genetic mutations ability of non-steroidal anti-inflammatory drugs and statins to (such as those found in APP and presenilins) or polymor- reduce Ab production, a feat which could also be achieved by phisms (such as the apolipoprotein E4 e-allele) that predis- Rac1 inhibition. Detailed understanding of the underlying poses an individual to early or late-onset Alzheimer’s disease. mechanisms of action of these novel modulators of APP In recent years, several classes of molecule with modulating processing, as well as insights into the molecular neur