Proteolytic cleavage of the amyloid protein from the amyloid protein precursor (APP) by APP secretases is a key event in Alzheimer's disease (AD) pathogenesis. α-Secretases cleave APP within the amyloid sequences, whereas β- and γ-secretases cleave on the N- and C-terminal ends respectively. The transmembrane aspartyl protease BACE has been identified as β-secretase and several proteases (ADAM-10, TACE, PC7) may be α-secretases. A number of studies have suggested that presenilins could be γ-secretases, although this remains to be demonstrated conclusively. Inhibition of β- and γ-secretase, or stimulation of α-secretase, is a rational strategy for therapeutic intervention in AD.
