Amyloid precursor protein secretase

Secretases are enzymes that 'snip' pieces off a longer protein that is embedded in the cell membrane. Secretases are enzymes that 'snip' pieces off a longer protein that is embedded in the cell membrane. Among other roles in the cell, secretases act on the amyloid precursor protein (APP) to cleave the protein into three fragments. Sequential cleavage by β-secretase (BACE) and γ-secretase produces the amyloid-β peptide fragment that aggregates into clumps called 'plaques' in the brains of Alzheimer's disease patients. If α-secretase acts on APP first instead of BACE, no amyloid-β is formed because α-secretase recognizes a target protein sequence closer to the cell surface than BACE. The non-pathogenic middle fragment formed by an α/γ cleavage sequence is called P3. The structure of the three secretases varies widely.