| PSEN2 - Presenilin 2
Type: Intramembrane aspartyl protease / catalytic γ-secretase complex subunit
Function: PSEN2 is a catalytic component of the γ-secretase complex, together with nicastrin, APH1, and PEN2. The complex performs intramembrane proteolysis of multiple substrates including amyloid precursor protein (APP) and Notch receptors. γ-Secretase cleavage of APP generates amyloid-β peptides including Aβ40 and Aβ42. PSEN2 also participates in endolysosomal, calcium, mitochondrial, and cellular signaling functions.
Alzheimer's Disease: ↕ Altered function. Pathogenic PSEN2 mutations cause rare autosomal-dominant familial Alzheimer's disease by altering γ-secretase processing of APP. Many disease-associated mutations increase the relative production of aggregation-prone Aβ42, producing an increased Aβ42/Aβ40 ratio. The primary Alzheimer's mechanism therefore reflects altered PSEN2/γ-secretase activity rather than a consistent increase or decrease in PSEN2 expression.
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