The β-secretase enzyme BACE1: A biochemical enigma for Alzheimer's disease.

Beta site amyloid precursor protein cleaving enzyme 1 (BACE1) is a rational target in Alzheimer's disease (AD) drug development due to its role in amyloidogenic cleavage of Amyloid precursor protein (APP) in generating Amyloid β (Aβ). This β-secretase cleaves not only Amyloid precursor protein (APP) and its homologues but also small series of substrate including neuregulin and β subunit of voltage gated sodium channel that play a very important role in the development and normal function of the brain. Moreover, BACE1 is modulated at the post translational level by several factors that are associated with both physiological and pathological functions. Since the discovery of BACE1 over a decade ago, medicinal chemistry and pharmacokinetics of BACE1 small molecule inhibitors have proven challenging for the treatment of Alzheimer's disease.