| PSEN1 — Presenilin 1 | |
|---|---|
| Symbol | PSEN1 |
| Full Name | Presenilin 1 |
| Chromosome | 14q24.3 |
| NCBI Gene | 5663 |
| Ensembl | ENSG00000118445 |
| OMIM | 104311 |
| UniProt | P49768 |
| Diseases | Alzheimer's Disease |
| Expression | Brain (neurons), heart, kidney |
| Key Mutations | |
| M146V, L286V, PSEN1dE9, A246E, H163R, L173P, C410Y | |
Psen1 — Presenilin 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
PSEN1 (Presenilin 1) is a critical gene on chromosome 14q24.3 encoding the presenilin-1 protein, the catalytic core of the gamma-secretase complex [1]. Mutations in PSEN1 are the most common cause of autosomal dominant familial Alzheimer's disease (FAD), accounting for up to 50% of cases [2]. Presenilin-1 is essential for amyloid precursor protein (APP) processing and the generation of amyloid-beta (Aβ) peptides, making it central to Alzheimer's disease pathogenesis.
Presenilin-1 (467 amino acids, ~52 kDa) is the enzymatic core of a multimeric complex:
PSEN1 is an aspartyl protease that:
Gamma-secretase cleaves numerous transmembrane proteins:
PSEN1 mutations alter APP processing:
Aβ Aggregation:
Other Effects:
PSEN1 mutations show:
Non-steroidal anti-inflammatory drugs (NSAIDs):
Gamma-secretase inhibitors:
The study of Psen1 — Presenilin 1 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.
[1] Wolfe MS. Secretase targets for Alzheimer's disease: gamma-secretase inhibitors and modulators. Biochim Biophys Acta. 2004;1690(1):67-74. PMID:14670631
[2] Ryman DC, Aisen PS, Bird TD, et al. Symptomatic, genetic, animal model, and biomarker studies in familial Alzheimer's disease. Alzheimers Dement. 2014;10(3):426-438. PMID:24331360
[3] Bentahir M, Nyabi O, Verhamme J, et al. Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms. J Neurochem. 2006;96(3):732-742. PMID:16405402
[4] De Strooper B, Saftig P, Craessaerts K, et al. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature. 1998;391(6665):387-390. PMID:9450751
[5] Haass C, Steiner H. Alzheimer disease gamma-secretase: a complex story of GxGD-type aspartic proteases. Cell. 2002;111(5):601-604. PMID:12438411
[6] Shen J, Kelleher RJ 3rd. The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism. Proc Natl Acad Sci U S A. 2007;104(2):403-409. PMID:17197420
[7] Kelleher RJ 3rd, Shen J. Genetics and disease: presenilin-1 and gamma-secretase. Cell. 2017;169(5):791-793. PMID:28575665