Presenilin-1 (PSEN1 (also commonly abbreviated as PS-1))

Presenilin‑1 is a multi-pass transmembrane protein encoded by the *PSEN1* gene. It serves as the **catalytic core** of the gamma-secretase complex, which is responsible for cleaving various type I transmembrane proteins, most notably amyloid precursor protein (APP). This cleavage generates amyloid beta peptides; accumulation and aggregation of these peptides are central features in Alzheimer's disease pathology. Mutations in *PSEN1* can lead to increased production of longer forms of amyloid beta that aggregate more readily, causing early-onset familial Alzheimer's disease. Presenilin‑1 also plays roles outside neurodegeneration—certain mutations have been linked to hidradenitis suppurativa via altered Notch signaling and impaired skin follicle function. Structurally, presenilin‑1 has nine transmembrane domains and undergoes endoproteolytic processing into N-terminal and C-terminal fragments that form an active heterodimer within cells[1][3].

Other names

PSEN1PS-1presenilin 1 protein

Inhibition or modulation of gamma-secretase activity to reduce amyloid beta production