Gene Symbol: PSEN2
Description: presenilin 2
Alias: AD3L, AD4, CMD1V, PS2, STM2, presenilin-2, AD3LP, AD5, Alzheimer disease 4, E5-1, PS-2, STM-2
Species: human
Products:     PSEN2

Top Publications

  1. Zhang W, Han S, McKeel D, Goate A, Wu J. Interaction of presenilins with the filamin family of actin-binding proteins. J Neurosci. 1998;18:914-22 pubmed
    Mutations in presenilin genes PS1 and PS2 account for approximately 50% of early-onset familial Alzheimer's disease (FAD)...
  2. Kang D, Yoon I, Repetto E, Busse T, Yermian N, Ie L, et al. Presenilins mediate phosphatidylinositol 3-kinase/AKT and ERK activation via select signaling receptors. Selectivity of PS2 in platelet-derived growth factor signaling. J Biol Chem. 2005;280:31537-47 pubmed
    The Alzheimer's disease-linked genes, PS1 and PS2, are required for intramembrane proteolysis of multiple type I proteins, including Notch and amyloid precursor protein...
  3. Duff K, Eckman C, Zehr C, Yu X, Prada C, Perez Tur J, et al. Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature. 1996;383:710-3 pubmed
    Mutations in the genes encoding amyloid-beta precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) are known to cause early-onset, autosomal dominant Alzheimer's disease...
  4. De Strooper B. Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO Rep. 2007;8:141-6 pubmed
    ..In this review, I evaluate the implications of this model for the amyloid-cascade hypothesis and for the efficacy of presenilin/gamma-secretase as a drug target. ..
  5. Kim T, Pettingell W, Jung Y, Kovacs D, Tanzi R. Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease. Science. 1997;277:373-6 pubmed
    ..familial Alzheimer's disease (FAD) are caused by mutations in the genes encoding the presenilin 1 (PS1) and PS2 proteins, both of which undergo regulated endoproteolytic processing...
  6. Jayadev S, Leverenz J, Steinbart E, Stahl J, Klunk W, Yu C, et al. Alzheimer's disease phenotypes and genotypes associated with mutations in presenilin 2. Brain. 2010;133:1143-54 pubmed publisher
    Mutations in presenilin 2 are rare causes of early onset familial Alzheimer's disease. Eighteen presenilin 2 mutations have been reported, although not all have been confirmed pathogenic...
  7. Buxbaum J, Choi E, Luo Y, Lilliehook C, Crowley A, Merriam D, et al. Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment. Nat Med. 1998;4:1177-81 pubmed
    ..Alzheimer disease (AD) cases are caused by mutations in the highly related genes presenilin 1 (PS1) and presenilin 2 (PS2)...
  8. Cruts M, Van Broeckhoven C. Presenilin mutations in Alzheimer's disease. Hum Mutat. 1998;11:183-90 pubmed
    ..In vivo and in vitro studies have linked PS mutations to amyloid deposition, an early pathological event in AD brains. ..
  9. Rogaev E, Sherrington R, Rogaeva E, Levesque G, Ikeda M, Liang Y, et al. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature. 1995;376:775-8 pubmed
    ..Our results also indicate that still other AD susceptibility genes exist. ..

More Information


  1. Mastrangelo P, Mathews P, Chishti M, Schmidt S, Gu Y, Yang J, et al. Dissociated phenotypes in presenilin transgenic mice define functionally distinct gamma-secretases. Proc Natl Acad Sci U S A. 2005;102:8972-7 pubmed
    ..of amyloid-beta precursor protein (APP) and Notch, and familial Alzheimer's disease (FAD) mutations in PS1 or PS2 genes shift APP cleavage from production of amyloid-beta (Abeta) 40 peptide to greater production of Abeta42...
  2. Wolfe M. When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO Rep. 2007;8:136-40 pubmed
    ..In this review, a unifying hypothesis is presented that puts forward a biochemical mechanism by which slower less-efficient forms of the protease can result in a greater proportion of 42-residue Abeta. ..
  3. Tomaino C, Bernardi L, Anfossi M, Costanzo A, Ferrise F, Gallo M, et al. Presenilin 2 Ser130Leu mutation in a case of late-onset "sporadic" Alzheimer's disease. J Neurol. 2007;254:391-3 pubmed
  4. Scacchi R, Gambina G, Moretto G, Corbo R. A mutation screening by DHPLC of PSEN1 and APP genes reveals no significant variation associated with the sporadic late-onset form of Alzheimer's disease. Neurosci Lett. 2007;418:282-5 pubmed
    ..been reportedly caused by mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), or presenilin-2 (PSEN2) genes, whereas the genetic component for the sporadic form is less clear...
  5. Shirotani K, Tomioka M, Kremmer E, Haass C, Steiner H. Pathological activity of familial Alzheimer's disease-associated mutant presenilin can be executed by six different gamma-secretase complexes. Neurobiol Dis. 2007;27:102-7 pubmed
    ..complexes are active in APP processing and that all combinations of APH-1 variants with either FAD mutant PS1 or PS2 support pathogenic Abeta(42) production...
  6. Shinozaki K, Maruyama K, Kume H, Tomita T, Saido T, Iwatsubo T, et al. The presenilin 2 loop domain interacts with the mu-calpain C-terminal region. Int J Mol Med. 1998;1:797-9 pubmed
    b>Presenilin 2 (PS2) is a gene responsible for the early-onset familial Alzheimer's disease (AD). PS2 mutations are considered to be closely related to the pathogenesis of AD...
  7. Vito P, Wolozin B, Ganjei J, Iwasaki K, Lacana E, D ADAMIO L. Requirement of the familial Alzheimer's disease gene PS2 for apoptosis. Opposing effect of ALG-3. J Biol Chem. 1996;271:31025-8 pubmed
    ALG-3, a truncated mouse homologue of the chromosome 1 familial Alzheimer's disease gene PS2, rescues T hybridoma 3DO cells from T-cell receptor-induced apoptosis by inhibiting Fas ligand induction and Fas signaling...
  8. Tomita T, Maruyama K, Saido T, Kume H, Shinozaki K, Tokuhiro S, et al. The presenilin 2 mutation (N141I) linked to familial Alzheimer disease (Volga German families) increases the secretion of amyloid beta protein ending at the 42nd (or 43rd) residue. Proc Natl Acad Sci U S A. 1997;94:2025-30 pubmed the pathogenetic mechanisms of early-onset familial Alzheimer disease (FAD), we expressed cDNAs for wild-type PS2 and PS2 with the Volga German (N141I) mutation in cultured cells and then examined the metabolism of the ..
  9. Loetscher H, Deuschle U, Brockhaus M, Reinhardt D, Nelboeck P, Mous J, et al. Presenilins are processed by caspase-type proteases. J Biol Chem. 1997;272:20655-9 pubmed
    Presenilin 1 (PS1) and presenilin 2 (PS2) are endoproteolytically processed in vivo and in cell transfectants to yield 27-35-kDa N-terminal and 15-24-kDa C-terminal fragments...
  10. Li J, Xu M, Zhou H, Ma J, Potter H. Alzheimer presenilins in the nuclear membrane, interphase kinetochores, and centrosomes suggest a role in chromosome segregation. Cell. 1997;90:917-27 pubmed
    ..We discuss a pathogenic pathway for familial Alzheimer's disease in which defective presenilin function causes chromosome missegregation during mitosis, resulting in apoptosis and/or trisomy 21 mosaicism. ..
  11. Walter J, Capell A, Grunberg J, Pesold B, Schindzielorz A, Prior R, et al. The Alzheimer's disease-associated presenilins are differentially phosphorylated proteins located predominantly within the endoplasmic reticulum. Mol Med. 1996;2:673-91 pubmed
    ..Selective phosphorylation of PS-2 proteins within the acidic domain missing in PS-1 indicates differences in the biological functions and regulation of the two highly homologous proteins. ..
  12. Marcon G, di Fede G, Giaccone G, Rossi G, Giovagnoli A, Maccagnano E, et al. A novel Italian presenilin 2 gene mutation with prevalent behavioral phenotype. J Alzheimers Dis. 2009;16:509-11 pubmed publisher
    ..far, more than 160 mutations in the Presenilin 1 gene (PSEN1) and approximately 10 mutations in the homologous Presenilin 2 gene (PSEN2) have been identified...
  13. Liu B, Wang L, Shen L, Shen M, Guo X, Wang T, et al. RNAi-mediated inhibition of presenilin 2 inhibits glioma cell growth and invasion and is involved in the regulation of Nrg1/ErbB signaling. Neuro Oncol. 2012;14:994-1006 pubmed publisher
    ..In this study, we found that the protein expression of presenilin 2 (PS2) was significantly increased in glioma tissues, at least partially because of promoter demethylation...
  14. Levy Lahad E, Wijsman E, Nemens E, Anderson L, Goddard K, Weber J, et al. A familial Alzheimer's disease locus on chromosome 1. Science. 1995;269:970-3 pubmed
    ..A 112-base pair allele of D1S479 co-segregated with the disease in five of seven families, which is consistent with a common genetic founder. This study demonstrates the presence of an AD locus on chromosome 1q31-42. ..
  15. Arango D, Cruts M, Torres O, Backhovens H, Serrano M, Villareal E, et al. Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia. Am J Med Genet. 2001;103:138-43 pubmed
    Nearly all mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid beta precursor protein (APP) genes lead to early-onset Alzheimer disease (EOAD, onset age at or before 65 years)...
  16. Wolozin B, Iwasaki K, Vito P, Ganjei J, Lacana E, Sunderland T, et al. Participation of presenilin 2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation. Science. 1996;274:1710-3 pubmed
    Overexpression of the familial Alzheimer's disease gene Presenilin 2 (PS2) in nerve growth factor-differentiated PC12 cells increased apoptosis induced by trophic factor withdrawal or beta-amyloid...
  17. To M, Gokgoz N, Doyle T, Donoviel D, Knight J, Hyslop P, et al. Functional characterization of novel presenilin-2 variants identified in human breast cancers. Oncogene. 2006;25:3557-64 pubmed
    ..Nonetheless, these results collectively suggest that the novel PS-2 alleles described here, especially R71W, affect PS-2 function and may potentially confer a moderate risk of susceptibility to breast cancer. ..
  18. Kovacs D, Fausett H, Page K, Kim T, Moir R, Merriam D, et al. Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells. Nat Med. 1996;2:224-9 pubmed
    ..These two novel genes, presenilin 1 (PS1) and presenilin 2 (PS2) are members of an evolutionarily conserved gene family...
  19. Stabler S, Ostrowski L, Janicki S, Monteiro M. A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein. J Cell Biol. 1999;145:1277-92 pubmed
    ..We report here the identification of a calcium-binding protein, calmyrin, that interacts preferentially with presenilin 2 (PS2)...
  20. Cruts M, van Duijn C, Backhovens H, Van den Broeck M, Wehnert A, Serneels S, et al. Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease. Hum Mol Genet. 1998;7:43-51 pubmed
    ..Further, polymorphisms were detected in the promoter and the 5'-non-coding region of PS -1 and in intronic and exonic sequences of PS -2 that will be useful in genetic association studies. ..
  21. Bergen A, Kaing S, ten Brink J, Gorgels T, Janssen S. Gene expression and functional annotation of human choroid plexus epithelium failure in Alzheimer's disease. BMC Genomics. 2015;16:956 pubmed publisher
    ..Remarkably, the expression of a number of genes known to be involved in AD, such as APP, PSEN1, PSEN2, TTR and CLU is moderate to high and remains stable in both healthy and affected CPE...
  22. Pineda G, Shen Z, de Albuquerque C, Reynoso E, Chen J, Tu C, et al. Proteomics studies of the interactome of RNA polymerase II C-terminal repeated domain. BMC Res Notes. 2015;8:616 pubmed publisher
    ..We also showed that the CID from four mammalian proteins interacted with pS2-phosphorylated but not pY1pS2-doubly phosphorylated CTD-peptides...
  23. Qin X, Wang Y, Paudel H. Inhibition of Early Growth Response 1 in the Hippocampus Alleviates Neuropathology and Improves Cognition in an Alzheimer Model with Plaques and Tangles. Am J Pathol. 2017;187:1828-1847 pubmed publisher
    ..precursor protein (APP) metabolites (secreted APP?, C99, A?40, and A?42) but has no effect on presenilin 1 and presenilin 2. In hippocampal primary neurons, Egr-1 binds to BACE-1 and p35 promoters, enhances tau phosphorylation, ..
  24. Hernandez Zimbron L, Perez Hernández M, Torres Romero A, Gorostieta Salas E, Gonzalez Salinas R, Gulias Cañizo R, et al. Markers of Alzheimer's Disease in Primary Visual Cortex in Normal Aging in Mice. Biomed Res Int. 2017;2017:3706018 pubmed publisher
    ..These results provide a comprehensive framework for the role of A?42 in visual loss due to inflammation present with aging and offer some clues for fruitful avenues for the study of healthy aging...
  25. Delabio R, Rasmussen L, Mizumoto I, Viani G, Chen E, Villares J, et al. PSEN1 and PSEN2 gene expression in Alzheimer's disease brain: a new approach. J Alzheimers Dis. 2014;42:757-60 pubmed publisher
    Presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes encode the major component of y-secretase, which is responsible for sequential proteolytic cleavages of amyloid precursor proteins and the subsequent formation of amyloid-? peptides...
  26. Pack Chung E, Meyers M, Pettingell W, Moir R, Brownawell A, Cheng I, et al. Presenilin 2 interacts with sorcin, a modulator of the ryanodine receptor. J Biol Chem. 2000;275:14440-5 pubmed
    ..We report here the molecular interaction of the large hydrophilic loop region of presenilin 2 (PS2) with sorcin, a penta-EF-hand Ca(2+)-binding protein that serves as a modulator of the ryanodine receptor ..
  27. Li L, Santarsiero B, Bouvier M. Structure of the Adenovirus Type 4 (Species E) E3-19K/HLA-A2 Complex Reveals Species-Specific Features in MHC Class I Recognition. J Immunol. 2016;197:1399-407 pubmed publisher
    ..We report the x-ray crystal structure of the Ad type 4 (Ad4) E3-19K of species E bound to HLA-A2 at 2.64-Å resolution...
  28. Guimarães V, Rodríguez Castellón E, Algarra M, Rocha F, Bobos I. Influence of pH, layer charge location and crystal thickness distribution on U(VI) sorption onto heterogeneous dioctahedral smectite. J Hazard Mater. 2016;317:246-258 pubmed publisher
    The UO2(2+) adsorption on smectite (samples BA1, PS2 and PS3) with a heterogeneous structure was investigated at pH 4 (I=0.02M) and pH 6 (I=0...
  29. Parra Damas A, Rubió Ferrarons L, Shen J, Saura C. CRTC1 mediates preferential transcription at neuronal activity-regulated CRE/TATA promoters. Sci Rep. 2017;7:18004 pubmed publisher
    ..These results indicate that neuronal activity induces a preferential binding of CRTC1 to the transcriptional complex in CRE/TATA-containing promoters to engage activity-dependent transcription in neurons. ..
  30. Mirinics Z, Calafat J, Udby L, Lovelock J, Kjeldsen L, Rothermund K, et al. Identification of the presenilins in hematopoietic cells with localization of presenilin 1 to neutrophil and platelet granules. Blood Cells Mol Dis. 2002;28:28-38 pubmed
    Most cases of familial Alzheimer disease (AD) are caused by mutations in presenilin 1 (PS1) and presenilin 2 (PS2)...
  31. Hayama T, Murakami K, Watanabe T, Maeda R, Kamata M, Kondo S. Single administration of a novel γ-secretase modulator ameliorates cognitive dysfunction in aged C57BL/6J mice. Brain Res. 2016;1633:52-61 pubmed publisher
    Mutations in presenilin 1 (PS1) and presenilin 2 (PS2) are known to cause early onset of Alzheimer's disease (AD)...
  32. Vinogradov E, Aubry A, Logan S. Structural characterization of wall and lipidated polysaccharides from Clostridium perfringens ATCC 13124. Carbohydr Res. 2017;448:88-94 pubmed publisher
    ..The minor polysaccharide PS2 had a linear regular structure with a -4-α-Rha-3-β-Gal-4-β-GalNAc3PCho- repeating unit, where PCho ..
  33. Thonberg H, Chiang H, Lilius L, Forsell C, Lindström A, Johansson C, et al. Identification and description of three families with familial Alzheimer disease that segregate variants in the SORL1 gene. Acta Neuropathol Commun. 2017;5:43 pubmed publisher
    ..Mutations in one of the three genes: amyloid beta precursor protein (APP), presenilin 1 (PSEN1) or presenilin 2 (PSEN2) can be disease causing...
  34. Zatti G, Ghidoni R, Barbiero L, Binetti G, Pozzan T, Fasolato C, et al. The presenilin 2 M239I mutation associated with familial Alzheimer's disease reduces Ca2+ release from intracellular stores. Neurobiol Dis. 2004;15:269-78 pubmed
    ..We here show, for the first time, the effect of the recently described PS2 FAD-associated M239I mutation on two major parameters of intracellular Ca(2+) homeostasis: the Ca(2+) storing ..
  35. Li G, Bekris L, Leong L, Steinbart E, Shofer J, Crane P, et al. TOMM40 intron 6 poly-T length, age at onset, and neuropathology of AD in individuals with APOE ε3/ε3. Alzheimers Dement. 2013;9:554-61 pubmed publisher
    ..Thirty-two presenilin 1 (PSEN1) mutation carriers with AD, 27 presenilin 2 (PSEN2) mutation carriers with AD, 59 participants with late-onset AD (LOAD), and 168 autopsied subjects from a ..
  36. Biederer T, Cao X, Sudhof T, Liu X. Regulation of APP-dependent transcription complexes by Mint/X11s: differential functions of Mint isoforms. J Neurosci. 2002;22:7340-51 pubmed
    ..In view of their biochemical similarity, the functional differences among Mints are unexpected, suggesting that Mints 1 and 2 have a brain-specific function related to APP that is not executed by the ubiquitous Mint 3. ..
  37. Bak M, Das Gupta S, Wahler J, Lee H, Li X, Lee M, et al. Inhibitory Effects of γ- and δ-Tocopherols on Estrogen-Stimulated Breast Cancer In Vitro and In Vivo. Cancer Prev Res (Phila). 2017;10:188-197 pubmed publisher
    ..expression of cell proliferation-related genes such as cyclin D1 and c-Myc, and estrogen-related genes such as TFF/pS2, cathepsin D, and progesterone receptor in estrogen-stimulated MCF-7 cells in vitro Further, γ- and δ-..
  38. Fraering P, Ye W, Strub J, Dolios G, LaVoie M, Ostaszewski B, et al. Purification and characterization of the human gamma-secretase complex. Biochemistry. 2004;43:9774-89 pubmed
  39. Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, et al. Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature. 2000;407:48-54 pubmed
    Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2. Suppression of nicastrin expression in Caenorhabditis elegans embryos induces a subset of notch/glp-1 phenotypes similar to ..
  40. Rosenberg R, Lambracht Washington D, Yu G, Xia W. Genomics of Alzheimer Disease: A Review. JAMA Neurol. 2016;73:867-74 pubmed publisher
    ..A translational result of genomic research has been A?-reducing therapies including DNA A?42 vaccination as a promising approach to delay or prevent this disease. ..
  41. Kuzminov F, Gorbunov M. Energy dissipation pathways in Photosystem 2 of the diatom, Phaeodactylum tricornutum, under high-light conditions. Photosynth Res. 2016;127:219-35 pubmed publisher
    ..we quantify NPQ-induced alterations in light-harvesting processes and photochemical reactions in Photosystem 2 (PS2) in the pennate diatom Phaeodactylum tricornutum...
  42. Cruchaga C, Haller G, Chakraverty S, Mayo K, Vallania F, Mitra R, et al. Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families. PLoS ONE. 2012;7:e31039 pubmed publisher
    Pathogenic mutations in APP, PSEN1, PSEN2, MAPT and GRN have previously been linked to familial early onset forms of dementia...
  43. Khati P, Chaudhary P, Gangola S, Bhatt P, Sharma A. Nanochitosan supports growth of Zea mays and also maintains soil health following growth. 3 Biotech. 2017;7:81 pubmed publisher
    ..present study evaluated the effect of nanochitosan in combination with plant growth promoting rhizobacteria (PGPR), PS2 and PS10 on maize growth. The PGPR were earlier recognized as Bacillus spp. on the basis of 16S rDNA sequencing...
  44. Schulz J, Annaert W, Vandekerckhove J, Zimmermann P, De Strooper B, David G. Syndecan 3 intramembrane proteolysis is presenilin/gamma-secretase-dependent and modulates cytosolic signaling. J Biol Chem. 2003;278:48651-7 pubmed
    ..The cleavage is mediated by presenilin/gamma-secretase complex and negatively regulates the plasma membrane targeting of the transcriptional cofactor CASK. ..
  45. Manabe T, Ohe K, Katayama T, Matsuzaki S, Yanagita T, Okuda H, et al. HMGA1a: sequence-specific RNA-binding factor causing sporadic Alzheimer's disease-linked exon skipping of presenilin-2 pre-mRNA. Genes Cells. 2007;12:1179-91 pubmed
    Aberrant exon 5 skipping of presenilin-2 (PS2) pre-mRNA produces a deleterious protein isoform PS2V, which is almost exclusively observed in the brains of sporadic Alzheimer's disease patients...
  46. Nikisch G, Hertel A, Kiessling B, Wagner T, Krasz D, Hofmann E, et al. Three-year follow-up of a patient with early-onset Alzheimer's disease with presenilin-2 N141I mutation - case report and review of the literature. Eur J Med Res. 2008;13:579-84 pubmed
    ..associated with mutations in 3 different genes: the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes...
  47. Alves da Costa C, Mattson M, Ancolio K, Checler F. The C-terminal fragment of presenilin 2 triggers p53-mediated staurosporine-induced apoptosis, a function independent of the presenilinase-derived N-terminal counterpart. J Biol Chem. 2003;278:12064-9 pubmed
    ..We show first that overexpression of the presenilinase-derived maturation product of presenilin 2 (CTF-PS2) increases Abeta recovery, the production of which is almost abolished by a caspase 3 inhibitor and ..
  48. Hwang C, Park M, Choi M, Choi J, Oh K, Hwang D, et al. Acceleration of amyloidogenesis and memory impairment by estrogen deficiency through NF-κB dependent beta-secretase activation in presenilin 2 mutant mice. Brain Behav Immun. 2016;53:113-122 pubmed publisher
    ..Senile plaques composed of β-amyloid (Aβ) are a pathological hallmark of Alzheimer's disease. Presenilin 2 (PS2) mutations increase Aβ generation in the brains of AD patients...
  49. Lara P, Moon J, Hesketh P, Redman M, Williamson S, Akerley W, et al. SWOG S0709: Randomized Phase II Trial of Erlotinib versus Erlotinib Plus Carboplatin/Paclitaxel in Patients with Advanced Non-Small Cell Lung Cancer and Impaired Performance Status as Selected by a Serum Proteomics Assay. J Thorac Oncol. 2016;11:420-5 pubmed publisher
    ..with advanced-stage non-small cell lung cancer (NSCLC) and borderline performance status (performance status 2 [PS2]) are often excluded from clinical trials and platinum-based therapy...
  50. Savchenko T, Yanykin D, Khorobrykh A, Terentyev V, Klimov V, Dehesh K. The hydroperoxide lyase branch of the oxylipin pathway protects against photoinhibition of photosynthesis. Planta. 2017;245:1179-1192 pubmed publisher
    ..enhanced adaptability in response to high light treatment as evidenced by lower rate constant of photosystem 2 (PS2) photoinhibition and higher rate constant of PS2 recovery after photoinhibition...
  51. El Kadmiri N, Zaid N, Zaid Y, Tadevosyan A, Hachem A, Dube M, et al. Novel presenilin mutations within Moroccan patients with Early-Onset Alzheimer's Disease. Neuroscience. 2014;269:215-22 pubmed publisher
    ..Genetically, AD is caused by a mutation in one of at least 3 genes: presenilin 1 (PS1), presenilin 2 (PS2) and the amyloid precursor protein (APP)...
  52. Hoogenboom M, Campbell D, Béraud E, Dezeeuw K, Ferrier Pagès C. Effects of light, food availability and temperature stress on the function of photosystem II and photosystem I of coral symbionts. PLoS ONE. 2012;7:e30167 pubmed publisher
    ..Our results show that PS1 function is comparatively robust against temperature stress in both species, whereas PS2 and whole chain electron transport are susceptible to temperature stress...
  53. McGeer P, Kawamata T, McGeer E. Localization and possible functions of presenilins in brain. Rev Neurosci. 1998;9:1-15 pubmed
    ..The functions of the presenilins are not yet known, but available evidence points to pyramidal neurons as the most logical site for pathological change in AD. ..
  54. Kimberly W, Xia W, Rahmati T, Wolfe M, Selkoe D. The transmembrane aspartates in presenilin 1 and 2 are obligatory for gamma-secretase activity and amyloid beta-protein generation. J Biol Chem. 2000;275:3173-8 pubmed
    ..b>Presenilin 2 (PS2) shares substantial sequence and possibly functional homology with PS1...
  55. Jeon A, Böhm C, Chen F, Huo H, Ruan X, Ren C, et al. Interactome analyses of mature γ-secretase complexes reveal distinct molecular environments of presenilin (PS) paralogs and preferential binding of signal peptide peptidase to PS2. J Biol Chem. 2013;288:15352-66 pubmed publisher
    ..Another intramembrane protease, signal peptide peptidase, predominantly co-purified with PS2-containing γ-secretase complexes and was observed to influence Aβ production.
  56. Moussavi Nik S, Wilson L, Newman M, Croft K, Mori T, Musgrave I, et al. The BACE1-PSEN-A?PP regulatory axis has an ancient role in response to low oxygen/oxidative stress. J Alzheimers Dis. 2012;28:515-30 pubmed publisher
    ..We observe that the zebrafish AD-related genes bace1, psen1, psen2, appa, and appb all show increased mRNA levels under hypoxia...
  57. Walker E, Martinez M, Brunkan A, Goate A. Presenilin 2 familial Alzheimer's disease mutations result in partial loss of function and dramatic changes in Abeta 42/40 ratios. J Neurochem. 2005;92:294-301 pubmed
    ..disproportionately to amyloid beta (Abeta) peptide generation from beta-amyloid precursor protein (APP), whereas PS2 plays a more minor role...
  58. Ford D, Monteiro M. Studies of the role of ubiquitination in the interaction of ubiquilin with the loop and carboxyl terminal regions of presenilin-2. Biochemistry. 2007;46:8827-37 pubmed
    ..In the present study, we examined whether ubiquitination of presenilin-2 (PS2) is required for interaction with ubiquilin-1 by mutating lysine residues that may be targets for ubiquitination in ..
  59. Yu C, Marchani E, Nikisch G, Muller U, Nolte D, Hertel A, et al. The N141I mutation in PSEN2: implications for the quintessential case of Alzheimer disease. Arch Neurol. 2010;67:631-3 pubmed publisher
    ..The families from Fulda, Germany, and the American Volga German families with EOAD share the same N141I PSEN2 mutation on an identical haplotypic background...
  60. Brunello L, Zampese E, Florean C, Pozzan T, Pizzo P, Fasolato C. Presenilin-2 dampens intracellular Ca2+ stores by increasing Ca2+ leakage and reducing Ca2+ uptake. J Cell Mol Med. 2009;13:3358-69 pubmed publisher
    We have previously shown that familial Alzheimer's disease mutants of presenilin-2 (PS2) and, to a lesser extent, of presenilin-1 (PS1) lower the Ca(2+) concentration of intracellular stores...
  61. Jiao B, Tang B, Liu X, Xu J, Wang Y, Zhou L, et al. Mutational analysis in early-onset familial Alzheimer's disease in Mainland China. Neurobiol Aging. 2014;35:1957.e1-6 pubmed publisher
    Mutations of 3 causative genes, namely presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP), have been identified as the major causes of early-onset familial Alzheimer's disease (EOFAD)...
  62. Finckh U, Müller Thomsen T, Mann U, Eggers C, Marksteiner J, Meins W, et al. High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. Am J Hum Genet. 2000;66:110-7 pubmed
    ..Mutations in the genes encoding the presenilins (PS1 and PS2) and amyloid precursor protein (APP) are associated with FAD, whereas mutations in the prion protein (PrP) gene are ..
  63. Piscopo P, Manfredi A, Malvezzi Campeggi L, Crestini A, Spadoni O, Cherchi R, et al. Genetic study of Sardinian patients with Alzheimer's disease. Neurosci Lett. 2006;398:124-8 pubmed
    ..of genes involved in AD, such as the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2)...
  64. Capell A, Beher D, Prokop S, Steiner H, Kaether C, Shearman M, et al. Gamma-secretase complex assembly within the early secretory pathway. J Biol Chem. 2005;280:6471-8 pubmed
  65. Tanaka S, Nagashima H. Establishment of an Alzheimer's disease model with latent herpesvirus infection using PS2 and Tg2576 double transgenic mice. Exp Anim. 2017;: pubmed publisher
    ..We crossbred female PS2 mice with male Tg2576 hemi mice and chose PS2Tg2576 mice...
  66. Jamal S, Goyal S, Shanker A, Grover A. Computational Screening and Exploration of Disease-Associated Genes in Alzheimer's Disease. J Cell Biochem. 2017;118:1471-1479 pubmed publisher
    ..Various genes have been known to be involved which are APOE, PSEN1, PSEN2, and APP among others...
  67. Bronfman F. Metalloproteases and gamma-secretase: new membrane partners regulating p75 neurotrophin receptor signaling?. J Neurochem. 2007;103 Suppl 1:91-100 pubmed
    ..In this review, we argue that both sheddases and gamma-secretase are key membrane components regulating p75-mediated signaling transduction; therefore, further attention should be paid to their roles as p75 signaling regulators. ..
  68. Gallo M, Tomaino C, Puccio G, Frangipane F, Curcio S, Bernardi L, et al. Novel MAPT Val75Ala mutation and PSEN2 Arg62Hys in two siblings with frontotemporal dementia. Neurol Sci. 2010;31:65-70 pubmed publisher
    ..Moreover, the novel mutation identified merits further functional studies that would contribute to the unravelling of such a complex field. ..
  69. Sloan C, Shen L, West J, Wishart H, Flashman L, Rabin L, et al. Genetic pathway-based hierarchical clustering analysis of older adults with cognitive complaints and amnestic mild cognitive impairment using clinical and neuroimaging phenotypes. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:1060-9 pubmed publisher cluster are ABCB1, APBA1, BACE1, BACE2, BCL2, BCL2L1, CASP7, CHAT, CST3, DRD3, DRD5, IL6, LRP1, NAT1, and PSEN2. The greater associations with morphology endpoints suggests that changes in brain structure can be influenced by ..
  70. Annaert W, Esselens C, Baert V, Boeve C, Snellings G, Cupers P, et al. Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins. Neuron. 2001;32:579-89 pubmed
    The carboxyl terminus of presenilin 1 and 2 (PS1 and PS2) binds to the neuron-specific cell adhesion molecule telencephalin (TLN) in the brain...
  71. Fassler M, Li X, Kaether C. Polar transmembrane-based amino acids in presenilin 1 are involved in endoplasmic reticulum localization, Pen2 protein binding, and ?-secretase complex stabilization. J Biol Chem. 2011;286:38390-6 pubmed publisher
    ..Intriguingly, a charged aspartate in TMD4 is critical for ?-secretase activity, most likely by stabilizing the newly formed complex. ..
  72. Muchnik C, Olivar N, Dalmasso M, Azurmendi P, Liberczuk C, Morelli L, et al. Identification of PSEN2 mutation p.N141I in Argentine pedigrees with early-onset familial Alzheimer's disease. Neurobiol Aging. 2015;36:2674-7.e1 pubmed publisher
    b>Presenilin 2 gene (PSEN2) mutations account for <5% of all early-onset familial Alzheimer's disease (EOFAD) cases and only 13 have strong evidence for pathogenicity. We aimed to investigate the presence of PSEN2 mutation p...
  73. Shi Z, Wang Y, Liu S, Liu M, Liu S, Zhou Y, et al. Clinical and neuroimaging characterization of Chinese dementia patients with PSEN1 and PSEN2 mutations. Dement Geriatr Cogn Disord. 2015;39:32-40 pubmed publisher
    ..Mutations in 3 genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset AD...
  74. Roszak J, Smok Pieniążek A, Domeradzka Gajda K, Grobelny J, Tomaszewska E, Ranoszek Soliwoda K, et al. Inhibitory effect of silver nanoparticles on proliferation of estrogen-dependent MCF-7/BUS human breast cancer cells induced by butyl paraben or di-n-butyl phthalate. Toxicol Appl Pharmacol. 2017;337:12-21 pubmed publisher
    ..AgNPs also decreased transcription of the estrogen-responsive pS2 and progesterone receptor (PGR) genes but modulated expression neither of ER? nor ER? in MCF-7/BUS cells exposed to ..
  75. Kalachaveedu M, Raghavan D, Telapolu S, Kuruvilla S, Kedike B. Phytoestrogenic effect of Inula racemosa Hook f - A cardioprotective root drug in traditional medicine. J Ethnopharmacol. 2018;210:408-416 pubmed publisher
    ..RT-PCR analysis evaluated the mRNA expression of pS2 in these cells post exposure to ALT, IALT and SG...
  76. Ham S, Kim T, Lee S, Tang Y, Im H. MicroRNA Profiling in Aging Brain of PSEN1/PSEN2 Double Knockout Mice. Mol Neurobiol. 2018;55:5232-5242 pubmed publisher
    ..On the basis of bioinformatics databases, 30 hippocampal microRNAs and their putative targets of PSEN1/PSEN2 double knockout mice were included in 28 pathways such as the wnt signaling pathway and ubiquitin-mediated ..
  77. Taniguchi Y, Karlstrom H, Lundkvist J, Mizutani T, Otaka A, Vestling M, et al. Notch receptor cleavage depends on but is not directly executed by presenilins. Proc Natl Acad Sci U S A. 2002;99:4014-9 pubmed
    ..We conclude from these experiments that presenilins are critically required for Notch intracellular cleavage but are not themselves directly mediating the cleavage. ..
  78. Yang X, Dinuka Abeydeera N, Liu F, Egli M. Origins of the enhanced affinity of RNA-protein interactions triggered by RNA phosphorodithioate backbone modification. Chem Commun (Camb). 2017;53:10508-10511 pubmed publisher
    ..protein and its cognate RNA hairpin was used to evaluate changes in affinity as a result of phosphorodithioate (PS2) replacing phosphate by biolayer interferometry (BLI)...
  79. Perkins M, Louw du Toit R, Africander D. A comparative characterization of estrogens used in hormone therapy via estrogen receptor (ER)-? and -?. J Steroid Biochem Mol Biol. 2017;174:27-39 pubmed publisher
    ..Although E2 and E3 were equally efficacious and potent on the endogenous ERE-containing pS2 promoter in the MCF-7 BUS breast cancer cell line co-expressing ER? and ER?, E1 was less efficacious and ..
  80. Pérez Moreno J, Espina Zambrano A, García Calderón C, Estrada B. Kon-tiki enhances PS2 integrin adhesion and localizes its ligand, Thrombospondin, in the myotendinous junction. J Cell Sci. 2017;130:950-962 pubmed publisher
    ..conserved transmembrane Drosophila proteoglycan Kon-tiki (Kon, also known as Perdido) interacts with the ?PS2?PS integrin (?PS2 is encoded by inflated and ?PS by myospheroid) to mediate muscle-tendon adhesion...
  81. Sai X, Kawamura Y, Kokame K, Yamaguchi H, Shiraishi H, Suzuki R, et al. Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein. J Biol Chem. 2002;277:12915-20 pubmed
    ..We found that Herp interacts with both PS1 and PS2. Thus, Herp regulates PS-mediated Abeta generation, possibly through its binding to PS...
  82. Signorini S, Ghidoni R, Barbiero L, Benussi L, Binetti G. Prevalence of pathogenic mutations in an Italian clinical series of patients with familial dementia. Curr Alzheimer Res. 2004;1:215-8 pubmed
    ..identified which, when mutated, cause Familial Alzheimer disease (FAD): the presenilin-1 (PS1), the presenilin-2 (PS2) and the amyloid precursor protein (APP) genes...
  83. Beher D, Fricker M, Nadin A, Clarke E, Wrigley J, Li Y, et al. In vitro characterization of the presenilin-dependent gamma-secretase complex using a novel affinity ligand. Biochemistry. 2003;42:8133-42 pubmed
    ..This was also reflected by a co-distribution of both enzyme activities in subcellular fractions enriched for trans-Golgi network membranes. ..
  84. Finckh U, Kuschel C, Anagnostouli M, Patsouris E, Pantes G, Gatzonis S, et al. Novel mutations and repeated findings of mutations in familial Alzheimer disease. Neurogenetics. 2005;6:85-9 pubmed
    ..patients with a history of suspected familial Alzheimer disease (FAD) were screened for mutations in PSEN1, PSEN2, and APP, the known FAD genes encoding the presenilins (PS1 and PS2) and the amyloid precursor protein (APP)...
  85. Marambaud P, Alves Da Costa C, Ancolio K, Checler F. Alzheimer's disease-linked mutation of presenilin 2 (N141I-PS2) drastically lowers APPalpha secretion: control by the proteasome. Biochem Biophys Res Commun. 1998;252:134-8 pubmed
    ..disease (FAD) are due to inherited mutations located on two homologous proteins, presenilins 1 and 2 (PS1 and PS2) encoded by chromosomes 14 and 1, respectively...