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γ-Secretase is a protease complex, which catalyzes the final of two subsequent cleavages of the β-amyloid precursor protein (APP) to release the amyloid-β peptide (Aβ) implicated in Alzheimer’s disease (AD) pathogenesis. In human cells, six γ-secretase complexes exist, which are composed of either presenilin (PS) 1 or 2, the catalytic subunit, nicastrin, PEN-2, and either APH-1a (as S or L splice...
Presenilin (PS) proteins facilitate endoproteolysis of selected type I transmembrane proteins such as the Alzheimer's disease (AD) associated β-Amyloid precursor protein (βAPP) and Notch. βAPP is cleaved within its transmembrane domain by an aspartyl protease activity termed γ-secretase, which may be identical with PS1 and PS2. Notch also undergoes a PS-dependent intramembraneous proteolysis. A similar...
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