Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Two alternative transcripts of PSEN2 have been identified.
In melanocytic cells PSEN2 gene expression may be regulated by MITF.
^Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res.21 (6): 665–676. doi:10.1111/j.1755-148X.2008.00505.x. PMID19067971.
^Passer BJ, Pellegrini L, Vito P, Ganjei JK, D'Adamio L (August 1999). "Interaction of Alzheimer's presenilin-1 and presenilin-2 with Bcl-X(L). A potential role in modulating the threshold of cell death". J. Biol. Chem.274 (34): 24007–13. PMID10446169.
^Shinozaki K, Maruyama K, Kume H, Tomita T, Saido TC, Iwatsubo T et al. (May 1998). "The presenilin 2 loop domain interacts with the mu-calpain C-terminal region". Int. J. Mol. Med.1 (5): 797–9. PMID9852298.
^Buxbaum JD, Choi EK, Luo Y, Lilliehook C, Crowley AC, Merriam DE et al. (October 1998). "Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment". Nat. Med.4 (10): 1177–81. doi:10.1038/2673. PMID9771752.
^Choi EK, Zaidi NF, Miller JS, Crowley AC, Merriam DE, Lilliehook C et al. (June 2001). "Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2". J. Biol. Chem.276 (22): 19197–204. doi:10.1074/jbc.M008597200. PMID11278424.
^Tanahashi H, Tabira T (September 2000). "Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein". Hum. Mol. Genet.9 (15): 2281–9. PMID11001931.
^Morohashi Y, Hatano N, Ohya S, Takikawa R, Watabiki T, Takasugi N et al. (April 2002). "Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4". J. Biol. Chem.277 (17): 14965–75. doi:10.1074/jbc.M200897200. PMID11847232.
^Lee SF, Shah S, Li H, Yu C, Han W, Yu G (November 2002). "Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch". J. Biol. Chem.277 (47): 45013–9. doi:10.1074/jbc.M208164200. PMID12297508.
^Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A et al. (September 2000). "Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing". Nature407 (6800): 48–54. doi:10.1038/35024009. PMID10993067.
da Costa CA (2006). "Recent insights on the pro-apoptotic phenotype elicited by presenilin 2 and its caspase and presenilinase-derived fragments". Current Alzheimer research2 (5): 507–514. doi:10.2174/156720505774932278. PMID16375654.