Preemptive treatment for Alzheimer disease by regulation of secretase activities

Taisuke Tomita

Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo

β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) and γ-secretase are proteolytic enzymes required for the production of the amyloid-β peptide (Aβ), which is associated with Alzheimer disease (AD). These enzymes have emerged as a prime molecular target for reducing the brain Aβ levels. Recently, several BACE1 inhibitors have been developed in clinical trials to test the efficacy in AD patients and individuals with prodromal AD. This review summarizes the current status of the development of secretase inhibitors/modulators and the evaluation of their therapeutic potential against AD.

Address correspondence to Dr. Taisuke Tomita, Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo(7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan)