BACE1 in Alzheimer's disease.Clin Chim Acta. 2012 Dec 24; 414:171-8.CC
Targeting BACE1 (β-site APP cleaving enzyme 1 or β-secretase) is the focus of Alzheimer's disease (AD) research because this aspartyl protease is involved in the abnormal production of β amyloid plaques (Aβ), the hallmark of its pathophysiology. Evidence suggests that there is a strong connection between AD and BACE1. As such, strategies to inhibit Aβ formation in the brain should prove beneficial for AD treatment. Aβ, the product of the large type1 trans-membrane protein amyloid precursor protein (APP), is produced in a two-step proteolytic process initiated by BACE1 (β-secretase) and followed by γ-secretase. Due to its apparent rate limiting function, BACE1 appears to be a prime target to prevent Aβ generation in AD. Following its discovery, the BACE1 has been cloned, its structure solved, novel physiologic substrates discovered and numerous inhibitors developed. This review focuses on elucidating the role of BACE1 to facilitate drug development in the treatment of AD.