Amyloid precursor protein (APP(18-770)) is processed by one of two distinct proteolytic pathways; the non-amyloidogenic pathway where alpha-secretase cleaves APP at the cell surface within the A-beta domain, liberating APPs-alpha and the amyloidogenic pathway, where beta-secretase followed by gamma-secretase cleavages results in peptides which are the main fibril-forming peptides implicated in Alzheimer's disease. In the first step of the amyloidogenic pathway, the endosomal membrane protein beta-secretase 1 (BACE1) catalyses the cleavage of APP(18-770) within the ectodomain and liberates a soluble proteolytic fragment, termed soluble APP-beta (APPs-beta, APP(18-671)) and C99 (APP(672-770) (Baranello et al. 2015, Andrew et al. 2016). APP processing can occur in several endocytic and secretory pathways. For simplicity, the endosome has been chosen in this event.
Padmaraju, V, Lahiri, DK, Chopra, N, Sambamurti, K, Baranello, RJ, Pappolla, MA, Greig, NH, Bharani, KL
beta-aspartyl-peptidase activity of BACE1 [endosome membrane]
© 2023 Reactome
