Peptidases, proteases and amyloid beta-peptide catabolism

The formation of senile plaques containing amyloid beta peptides (Abeta peptides) as a major constituent plays a significant role in development of Alzheimer's disease. The concentration of Abeta peptides in the brain is determined by a combination of their rate of synthesis and their rate of clearance. Considerable effort has been expended in producing inhibitors of the beta and gamma secretases involved in the synthesis of the Abeta peptides. More recently interest in the mechanism of clearance of the Abeta peptides has emerged, as promoting Abeta peptide clearance represents an alternative therapeutic approach. It now appears that cleavage of Abeta peptide by peptidases and proteases represents the major mechanism of clearance. This review describes those peptidases and proteases implicated in Abeta peptide clearance, the evidence that these enzymes function in vivo, and how they may represent new therapeutic targets.