High resolution

Module 12: Figure APP processing

Processing of amyloid precursor protein (APP) by the γ-secretase complex.

APP is cleaved first by BACE to release sAPPβ leaving behind the CTFβ, which is the precursor that is cleaved by the γ-secretase complex. The enzymic component of this complex is presenilin, which has two fragments: the N-terminal fragment (NTF) that has six transmembrane (TM) domains and the C-terminal fragment (CTF) that has two TMs. TM 6 and 7 have intramembrane aspartate (D) residues that are part of the catalytic mechanism that cuts CTFβ in the middle of its intramembrane region to release β-amyloid (Aβ) to one side and APP intracellular domain (AICD) to the other side. The AICD together with various associated factors functions to activate gene transcription (for further details see Module 12: Figure amyloid cascade hypothesis).