Recent developments of structure based β-secretase inhibitors for Alzheimer's disease

The amyloid-beta (AD) peptide is the principal components of the senile plaques found in the brains of patients with Alzheimer's disease (AD). The poorly soluble 40-42 amino acid peptide, formed from the cleavage of the AD precursor protein (APP) by two proteases, is believed to play a central role in the pathogenesis of AD. beta-Secretase (memapsin 2, BACEI), a membrane-anchored aspartic protease, is responsible for the initial step of APP cleavage leading to the generation of AD. Identification and structural determination of beta-secretase have established it to be a primary drug target for AD therapy and stimulated active studies on the inhibitors of this protease. Here we review more recent developments in the design and testing of structure-based beta-secretase inhibitors.