BACE-1 is an aspartic protease and an integral membrane protein. It is the major β secretase, and together with the γ secretase, is responsible for generating the amyloid β peptide (Aβ) from the amyloid precursor protein (APP). Because Aβ is a major component of amyloid plaques, BACE-1 has been implicated in the onset and/or progression of Alzheimer's disease. High levels of BACE-1 activity are sufficient to elicit neurodegeneration and neurological decline in indicating that inhibiting BACE-1 may block not only Aβ-dependent but also Aβ-independent pahtogenic mechanisms. In addition to APP, BACE-1 also cleaves APP-like proteins 1 and 2, the cell adhesion protein P-selectin glycoprotein ligand-1 and β-galactoside α2,6-sialyltransferase, implying that BACE-1 may have additional functions involving the ectodomain shedding of membrane proteins. The purified rmBACE-1 corresponds to the ectodomain with the activity described above.
