BACE Inhibition as a Therapeutic Strategy for Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease and the most common cause of dementia. One of the characteristic hallmarks of AD brains upon post-mortem examination is the presence of amyloid plaques containing aggregates of the neurotoxic amyloid-β peptide Aβ. This peptide is produced from the amyloid precursor protein (APP) by proteolytic cleavage, firstly by BACE1 (β-site amyloid precursor protein cleaving enzyme 1 or β-secretase) and subsequently by γ-secretase. After Phase III, clinical trials of a γ-secretase inhibitor were abandoned due to adverse secondary effects, the focus has shifted to BACE1 as a key drug target in AD. Numerous BACE inhibitors ha..