| Presenilin-2 (PS2) | |
|---|---|
| Gene | PSEN2 |
| UniProt | O00287 |
| PDB | 4HO6, 5E2Z |
| Mol. Weight | 50 kDa (full-length), ~20 kDa (C-terminal fragment) |
| Localization | Endoplasmic reticulum, Golgi apparatus, mitochondria |
| Family | Presenilin family, aspartyl proteases |
| Diseases | Alzheimer's Disease, Familial Alzheimer's Disease |
Presenilin 2 (Ps2) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Presenilin-2 (PS2) is a multipass transmembrane aspartyl protease that plays a critical role in γ-secretase complex formation and amyloid precursor protein (APP) processing[1]. Along with presenilin-1 (PS1), PS2 is responsible for generating amyloid-β (Aβ) peptides, the primary constituents of amyloid plaques in Alzheimer's disease[2].
Presenilin-2 is a ~467 amino acid protein with:
The active enzyme requires assembly into the γ-secretase complex with three other subunits:
Presenilin-2, as part of the γ-secretase complex, catalyzes the intramembranous proteolysis of:
APP → α-secretase → sAPPα + C83 → γ-secretase → Aβ40
APP → β-secretase → sAPPβ + C99 → γ-secretase → Aβ42/Aβ43
PS2 tends to produce longer Aβ peptides (Aβ42, Aβ43) compared to PS1.
Over 40 PSEN2 mutations are linked to familial Alzheimer's disease (FAD):
[1]: Wolfe MS. The gamma-secretase complex: membrane-embedded proteolytic ensemble. J Neurochem. 2016;139 Suppl 2:39-52. PMID:26821143
[2]: Haass C, Selkoe DJ. Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide. Cell. 1993;73(6):1055-1058. PMID:8101482
[3]: Ryman NR, Lamb BT. Presenilin-2: more than an epsilon-cleaving protease. Mol Neurodegener. 2015;10(Suppl 1):S7. PMID:25925283
The study of Presenilin 2 (Ps2) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.