Peptide corresponding to amino acids 485 to 501 of human BACE (1)
Accumulation of the amyloid-b (Ab) plaque in the cerebral cortex is a critical event in the pathogenesis of Alzheimer’s disease. Ab peptide is generated by proteolytic cleavage of the b-amyloid protein precursor (APP) at b-and g-sites by two proteases. APP is first cleaved by b-secretase, producing a soluble derivative of the protein and a membrane anchored 99-amino acid carboxy-terminal fragment (C99). The C99 fragment serves as substrate for g-secretase to generate the 4kD amyloid-b peptide, which is deposited in the brains of all suffers of Alzheimer’s disease. The long-sought b-secretase was recently identified by several groups independently and designated beta-site APP cleaving enzyme (BACE) and aspartyl protease 2 (Asp2) (1-4). BACE/Asp2 is a novel transmembrane aspartic protease and colocalizes with APP.
