A family of peptidases involved in processing of membrane-bound precursor molecules. α-Secretase (ADAM10, EC 184.108.40.206, 748 aa) cleaves amyloid precursor protein (APP) to produce the soluble nonamyloidogenic product sAPPα; this prevents the formation of amyloid (beta peptide. It also has TNF-convertase activity. (Beta-Secretase (BACE-1, beta-site APP cleaving enzyme 1, EC 220.127.116.11, 501 aa) is an integral membrane aspartic peptidase that generates the N-terminus of the β-amyloid protein from APP. Further cleavage is then carried out by γ-secretase, a multiprotein complex responsible for the intramembranous cleavage of the amyloid precursor protein (APP) and other type I transmembrane proteins such as notch and E-cadherin. There are four components, presenilin, nicastrin, APH-1, and PEN-2, all of which are required for activity; a fifth component, CD147, seems to have a regulatory role. Mutations in presenilin are a risk factor for Alzheimer's disease.
Subjects: Medicine and Health — Chemistry.