PSEN2 Gene

The PSEN2 gene (PSEN2 stands for "presenilin 2") is a protein-coding gene located on chromosome 1q42.13. Two alternatively spliced transcript variants encoding different isoforms of PSEN2 have been identified.

In AD patients with a hereditary form of the disease, associations with mutations in the presenilin proteins (PSEN1 or PSEN2) or the amyloid precursor protein (APP) are detectable. These mutations lead to increased production of the longer form of amyloid-beta (the main component of amyloid deposits in AD brains). Presenilins are thought to regulate APP processing through their action on gamma-secretase, an enzyme that cleaves APP. Presenilins are involved in Notch receptor cleavage, so they either directly regulate gamma-secretase activity or act as protease enzymes themselves.

Diseases associated with PSEN2 include.

• Alzheimer's disease 4 (OMIM: 606889)
• dilated cardiomyopathy (ICD10CM:I42.0; OMIM:613697)
• acne inversa (see also acne inversa familial)

The gamma-secretase is a multi-subunit internal protease that cleaves within the transmembrane domain of its substrates. It is involved in the processing of Notch. The protease is an integral membrane protein and consists of four proteins:

• Presenilin
• Nicastrin
• APH-1 and
• PEN-2.

1. Lanoiselée HM et al (2017) APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS Med 14:e1002270.
2. Nomura T (2020) Hidradenitis Suppurativa as a Potential Subtype of Autoinflammatory Keratinization Disease. Front Immunol11:847.
3. Pink AE et al (2012) Mutations in the gamma-secretase genes NCSTN, PSENEN, and PSEN1 underlie rare forms of hidradenitis suppurativa (acne inversa). J Invest Dermatol 132: 2459-2461.
4. Vural S et al. (2021) Investigation of gamma secretase gene complex mutations in German population with hidradenitis suppurativa designate a complex polygenic heritage. J Eur Acad Dermatol Venereol 35:1386-1392 .