Psen2

Summary

Gene Symbol: Psen2
Description: presenilin 2
Alias: ALG-3, Ad4h, Alg3, PS-2, PS2, Psnl2, STM2, presenilin-2
Species: mouse
Products:     Psen2

Top Publications

  1. Steiner H, Winkler E, Edbauer D, Prokop S, Basset G, Yamasaki A, et al. PEN-2 is an integral component of the gamma-secretase complex required for coordinated expression of presenilin and nicastrin. J Biol Chem. 2002;277:39062-5 pubmed
    ..Here we identify PEN-2 as a critical component of PS1/gamma-secretase and PS2/gamma-secretase complexes. Strikingly, in the absence of PS1 and PS1/PS2, PEN-2 levels are strongly reduced...
  2. Wang R, Tang P, Wang P, Boissy R, Zheng H. Regulation of tyrosinase trafficking and processing by presenilins: partial loss of function by familial Alzheimer's disease mutation. Proc Natl Acad Sci U S A. 2006;103:353-8 pubmed
    ..Our results identify Tyr and related proteins as physiological substrates of PS and link gamma-secretase activity with intracellular protein transport. ..
  3. Lee S, Hwang D, Kim Y, Lee J, Shin I, Oh K, et al. PS2 mutation increases neuronal cell vulnerability to neurotoxicants through activation of caspase-3 by enhancing of ryanodine receptor-mediated calcium release. FASEB J. 2006;20:151-3 pubmed
  4. Chen Q, Nakajima A, Choi S, Xiong X, Sisodia S, Tang Y. Adult neurogenesis is functionally associated with AD-like neurodegeneration. Neurobiol Dis. 2008;29:316-26 pubmed
    ..Therefore, to enhance endogenous neurogenesis at early stages of neurodegeneration may be a valuable strategy to delay neurodegenerative progress. ..
  5. Zhang C, Wu B, Beglopoulos V, Wines Samuelson M, Zhang D, Dragatsis I, et al. Presenilins are essential for regulating neurotransmitter release. Nature. 2009;460:632-6 pubmed publisher
  6. 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...
  7. Thinakaran G, Borchelt D, Lee M, Slunt H, Spitzer L, Kim G, et al. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron. 1996;17:181-90 pubmed
    ..of early-onset cases of familial Alzheimer's disease (FAD) are linked to mutations in two related genes, PS1 and PS2, located on chromosome 14 and 1, respectively...
  8. Ong C, Sedy J, Murphy K, Kopan R. Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisition. PLoS ONE. 2008;3:e2823 pubmed publisher
    ..The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation. ..
  9. Hilton M, Tu X, Wu X, Bai S, Zhao H, Kobayashi T, et al. Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat Med. 2008;14:306-14 pubmed publisher
    ..Thus, mesenchymal progenitors may be expanded in vitro by activating the Notch pathway, whereas bone formation in vivo may be enhanced by transiently suppressing this pathway. ..

More Information

Publications77

  1. Steiner H, Duff K, Capell A, Romig H, Grim M, Lincoln S, et al. A loss of function mutation of presenilin-2 interferes with amyloid beta-peptide production and notch signaling. J Biol Chem. 1999;274:28669-73 pubmed
    ..Although Alzheimer's disease-associated mutations in the homologous presenilin (PS2) gene elevate amyloid beta-peptide (Abeta42) production like PS1 mutations, here we demonstrate that a gene ..
  2. Rocher Ros V, Marco S, Mao J, Gines S, Metzger D, Chambon P, et al. Presenilin modulates EGFR signaling and cell transformation by regulating the ubiquitin ligase Fbw7. Oncogene. 2010;29:2950-61 pubmed publisher
    ..These findings establish a novel role for PS on epidermal growth and transformation by reciprocally regulating the EGFR and Notch signaling pathways through Fbw7. ..
  3. Frånberg J, Svensson A, Winblad B, Karlstrom H, Frykman S. Minor contribution of presenilin 2 for ?-secretase activity in mouse embryonic fibroblasts and adult mouse brain. Biochem Biophys Res Commun. 2011;404:564-8 pubmed publisher
    ..PS and Aph-1 exist as different homologs (PS1/PS2 and Aph-1a/Aph-1b, respectively), which generates a variation in complex composition...
  4. Pan Y, Liu Z, Shen J, Kopan R. Notch1 and 2 cooperate in limb ectoderm to receive an early Jagged2 signal regulating interdigital apoptosis. Dev Biol. 2005;286:472-82 pubmed
    ..Thus, Notch signaling plays a non-autonomous role in digit septation. ..
  5. Huppert S, Ilagan M, De Strooper B, Kopan R. Analysis of Notch function in presomitic mesoderm suggests a gamma-secretase-independent role for presenilins in somite differentiation. Dev Cell. 2005;8:677-88 pubmed
    ..These data clarify multiple roles for Notch signaling during segmentation and suggest that the earliest stages of somitogenesis are regulated by both Notch-dependent and Notch-independent functions of presenilin. ..
  6. Pan Y, Lin M, Tian X, Cheng H, Gridley T, Shen J, et al. gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis. Dev Cell. 2004;7:731-43 pubmed
  7. Beglopoulos V, Sun X, Saura C, Lemere C, Kim R, Shen J. Reduced beta-amyloid production and increased inflammatory responses in presenilin conditional knock-out mice. J Biol Chem. 2004;279:46907-14 pubmed
  8. Jiang X, Zhang D, Shi J, Chen Y, Zhang P, Mei B. Increased inflammatory response both in brain and in periphery in presenilin 1 and presenilin 2 conditional double knock-out mice. J Alzheimers Dis. 2009;18:515-23 pubmed publisher
  9. Qyang Y, Chambers S, Wang P, Xia X, Chen X, Goodell M, et al. Myeloproliferative disease in mice with reduced presenilin gene dosage: effect of gamma-secretase blockage. Biochemistry. 2004;43:5352-9 pubmed
    Mammalian presenilins (PS) consist of two highly homologous proteins, PS1 and PS2. Because of their indispensable activity in the gamma-secretase cleavage of amyloid precursor protein to generate Abeta peptides, inhibition of PS gamma-..
  10. Zhang H, Sun S, Herreman A, De Strooper B, Bezprozvanny I. Role of presenilins in neuronal calcium homeostasis. J Neurosci. 2010;30:8566-80 pubmed publisher
    ..experiments with primary neuronal cultures from conditional presenilin double-knock-out mice (PS1(dTAG/dTAG), PS2(-/-)) and from triple-transgenic AD mice (KI-PS1(M146V), Thy1-APP(KM670/671NL), Thy1-tau(P301L))...
  11. Han W, Ji T, Wang L, Yan L, Wang H, Luo Z, et al. Abnormalities in periodontal and salivary tissues in conditional presenilin 1 and presenilin 2 double knockout mice. Mol Cell Biochem. 2011;347:13-20 pubmed publisher
    We used forebrain-specific conditional presenilin 1 (PS1) and presenilin 2 (PS2) double knockout mice (dKO mice), which exhibit neurodegenerative disease-like symptoms, including inflammation of the brain and periphery, to investigate ..
  12. Chen F, Hasegawa H, Schmitt Ulms G, Kawarai T, Bohm C, Katayama T, et al. TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity. Nature. 2006;440:1208-12 pubmed
    The presenilin proteins (PS1 and PS2) and their interacting partners nicastrin, aph-1 (refs 4, 5) and pen-2 (ref...
  13. Green K, Demuro A, Akbari Y, Hitt B, Smith I, Parker I, et al. SERCA pump activity is physiologically regulated by presenilin and regulates amyloid beta production. J Cell Biol. 2008;181:1107-16 pubmed publisher
    ..We show that SERCA activity is diminished in fibroblasts lacking both PS1 and PS2 genes, despite elevated SERCA2b steady-state levels, and we show that presenilins and SERCA physically interact...
  14. Kashiwa A, Yoshida H, Lee S, Paladino T, Liu Y, Chen Q, et al. Isolation and characterization of novel presenilin binding protein. J Neurochem. 2000;75:109-16 pubmed
    ..immunohistochemical studies and cell fractionation analysis show that PBP redistributes from cytoplasm to membranes in the presence of PS. In addition, PBP is deficient in the soluble fraction of sporadic AD brains. ..
  15. Donoviel D, Hadjantonakis A, Ikeda M, Zheng H, Hyslop P, Bernstein A. Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev. 1999;13:2801-10 pubmed
    ..There are two highly homologous presenilin genes in mammals, presenilin 1 (PS1) and presenilin 2 (PS2). In mice, inactivation of PS1 leads to developmental defects that culminate in a perinatal lethality...
  16. Price D, Tanzi R, Borchelt D, Sisodia S. Alzheimer's disease: genetic studies and transgenic models. Annu Rev Genet. 1998;32:461-93 pubmed
  17. Tabuchi K, Chen G, Sudhof T, Shen J. Conditional forebrain inactivation of nicastrin causes progressive memory impairment and age-related neurodegeneration. J Neurosci. 2009;29:7290-301 pubmed publisher
  18. Laky K, Fowlkes B. Presenilins regulate alphabeta T cell development by modulating TCR signaling. J Exp Med. 2007;204:2115-29 pubmed
  19. De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, Annaert W, et al. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature. 1998;391:387-90 pubmed
    ..Our results indicate that mutations in PS1 that manifest clinically cause a gain of function and that inhibition of PS1 activity is a potential target for anti-amyloidogenic therapy in Alzheimer's disease. ..
  20. Hébert S, Serneels L, Dejaegere T, Horré K, Dabrowski M, Baert V, et al. Coordinated and widespread expression of gamma-secretase in vivo: evidence for size and molecular heterogeneity. Neurobiol Dis. 2004;17:260-72 pubmed
    ..In conclusion, our results suggest that gamma-secretase is a heterogeneous family of protein complexes widely expressed in the adult organism. ..
  21. Dong S, Li C, Wu P, Tsien J, Hu Y. Environment enrichment rescues the neurodegenerative phenotypes in presenilins-deficient mice. Eur J Neurosci. 2007;26:101-12 pubmed
    ..Furthermore, the beneficial effects of EE may be associated with the inhibition of the expression of immunity and inflammation-related genes in the brain. ..
  22. Saura C, Choi S, Beglopoulos V, Malkani S, Zhang D, Shankaranarayana Rao B, et al. Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron. 2004;42:23-36 pubmed
    ..These results define essential roles and molecular targets of presenilins in synaptic plasticity, learning and memory, and neuronal survival in the adult cerebral cortex. ..
  23. Ghidoni R, Paterlini A, Benussi L, Binetti G. Presenilin 2 is secreted in mouse primary neurons: a release enhanced by apoptosis. Mech Ageing Dev. 2007;128:350-3 pubmed
    Presenilin 1 (PS1) and presenilin 2 (PS2) are homologous transmembrane proteins genetically associated with Alzheimer disease...
  24. Saxena M, Schroeter E, Mumm J, Kopan R. Murine notch homologs (N1-4) undergo presenilin-dependent proteolysis. J Biol Chem. 2001;276:40268-73 pubmed
    ..Despite a high degree of structural homology and the presenilin-dependent activity of truncated Notch proteins, the extent that this reflects functional redundancy is unknown. ..
  25. Takeda T, Asahi M, Yamaguchi O, Hikoso S, Nakayama H, Kusakari Y, et al. Presenilin 2 regulates the systolic function of heart by modulating Ca2+ signaling. FASEB J. 2005;19:2069-71 pubmed
    Genetic studies of families with familial Alzheimer's disease have implicated presenilin 2 (PS2) in the pathogenesis of this disease. PS2 is ubiquitously expressed in various tissues including hearts...
  26. Yagi T, Giallourakis C, Mohanty S, Scheidig C, Shen J, Zheng H, et al. Defective signal transduction in B lymphocytes lacking presenilin proteins. Proc Natl Acad Sci U S A. 2008;105:979-84 pubmed publisher
    ..predictions, we analyzed mice carrying a conditional allele of PS1 and a germ line-inactivating allele of PS2, together with Cre site-specific recombinase expression under the influence of CD19 control sequences...
  27. Hass M, Yankner B. A {gamma}-secretase-independent mechanism of signal transduction by the amyloid precursor protein. J Biol Chem. 2005;280:36895-904 pubmed
    ..Thus, APP may signal to the nucleus by a gamma-secretase-independent mechanism that involves membrane sequestration and phosphorylation of Tip60. ..
  28. Lai M, Chen E, Crouthamel M, DiMuzio Mower J, Xu M, Huang Q, et al. Presenilin-1 and presenilin-2 exhibit distinct yet overlapping gamma-secretase activities. J Biol Chem. 2003;278:22475-81 pubmed
    Presenilin-1 (PS1) and presenilin 2 (PS2) are proposed to be transmembrane aspartyl proteases that cleave amyloid precursor protein and Notch...
  29. 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...
  30. Ezratty E, Stokes N, Chai S, Shah A, Williams S, Fuchs E. A role for the primary cilium in Notch signaling and epidermal differentiation during skin development. Cell. 2011;145:1129-41 pubmed publisher
    ..These findings unveil temporally and spatially distinct functions for primary cilia at the nexus of signaling, proliferation, and differentiation. ..
  31. Wong P, Zheng H, Chen H, Becher M, Sirinathsinghji D, Trumbauer M, et al. Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm. Nature. 1997;387:288-92 pubmed
    ..dominant inheritance of mutations in genes encoding the amyloid precursor protein, presenilin 1 (PS1) and presenilin 2 (PS2). Mutations in PS1 are linked to about 25% of cases of early-onset familial Alzheimer's disease...
  32. Feng R, Wang H, Wang J, Shrom D, Zeng X, Tsien J. Forebrain degeneration and ventricle enlargement caused by double knockout of Alzheimer's presenilin-1 and presenilin-2. Proc Natl Acad Sci U S A. 2004;101:8162-7 pubmed
    ..Thus, our study demonstrates that presenilins are essential for the ongoing maintenance of cortical structures and function. ..
  33. Ferjentsik Z, Hayashi S, Dale J, Bessho Y, Herreman A, De Strooper B, et al. Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites. PLoS Genet. 2009;5:e1000662 pubmed publisher
    ..components of the Notch pathway, such as Lunatic fringe (Lfng), Hes7, Rbpj, and presenilin1/presenilin2 (Psen1/Psen2), and by pharmacological blocking of the Notch pathway...
  34. Yu H, Saura C, Choi S, Sun L, Yang X, Handler M, et al. APP processing and synaptic plasticity in presenilin-1 conditional knockout mice. Neuron. 2001;31:713-26 pubmed
    ..These results demonstrate that inactivation of PS1 function in the adult cerebral cortex leads to reduced Abeta generation and subtle cognitive deficits without affecting expression of Notch downstream genes. ..
  35. Herreman A, Hartmann D, Annaert W, Saftig P, Craessaerts K, Serneels L, et al. Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency. Proc Natl Acad Sci U S A. 1999;96:11872-7 pubmed
    Mutations in the homologous presenilin 1 (PS1) and presenilin 2 (PS2) genes cause the most common and aggressive form of familial Alzheimer's disease...
  36. Lee M, Slunt H, Martin L, Thinakaran G, Kim G, Gandy S, et al. Expression of presenilin 1 and 2 (PS1 and PS2) in human and murine tissues. J Neurosci. 1996;16:7513-25 pubmed
    Mutations in genes encoding related proteins, termed presenilin 1 (PS1) and presenilin 2 (PS2), are linked to the majority of cases with early-onset familial Alzheimer's disease (FAD)...
  37. Vito P, Lacana E, D ADAMIO L. Interfering with apoptosis: Ca(2+)-binding protein ALG-2 and Alzheimer's disease gene ALG-3. Science. 1996;271:521-5 pubmed
    ..ALG-3, a partial complementary DNA that is homologous to the familial Alzheimer's disease gene STM2, rescues a T cell hybridoma from T cell receptor- and Fas-induced apoptosis...
  38. Dehvari N, Isacsson O, Winblad B, Cedazo Minguez A, Cowburn R. Presenilin regulates extracellular regulated kinase (Erk) activity by a protein kinase C alpha dependent mechanism. Neurosci Lett. 2008;436:77-80 pubmed publisher
    Presenilin (PS1 and PS2) mutations cause early-onset familial Alzheimer's disease (AD). In addition to affecting beta-amyloid precursor protein (APP) processing and Abeta generation, PSs regulate a number of signaling pathways...
  39. Dai D, Li L, Huebner A, Zeng H, Guevara E, Claypool D, et al. Planar cell polarity effector gene Intu regulates cell fate-specific differentiation of keratinocytes through the primary cilia. Cell Death Differ. 2013;20:130-8 pubmed publisher
  40. Ezratty E, Pasolli H, Fuchs E. A Presenilin-2-ARF4 trafficking axis modulates Notch signaling during epidermal differentiation. J Cell Biol. 2016;214:89-101 pubmed publisher
    ..Collectively, our findings raise the possibility that ARF4-dependent polarized exocytosis acts through the basal body-ciliary complex to spatially regulate Notch signaling during epidermal differentiation. ..
  41. Engin F, Yao Z, Yang T, Zhou G, Bertin T, Jiang M, et al. Dimorphic effects of Notch signaling in bone homeostasis. Nat Med. 2008;14:299-305 pubmed publisher
    ..Together, these findings highlight the potential dimorphic effects of Notch signaling in bone homeostasis and may provide direction for novel therapeutic applications. ..
  42. Jutras I, Laplante A, Boulais J, Brunet S, Thinakaran G, Desjardins M. Gamma-secretase is a functional component of phagosomes. J Biol Chem. 2005;280:36310-7 pubmed
    ..Finally, our results indicate that interferon-gamma stimulates gamma-secretase-dependent cleavages on phagosomes and that gamma-secretase activity may be involved in the phagocytic response of macrophages to inflammatory cytokines. ..
  43. Leem J, Vijayan S, Han P, Cai D, Machura M, Lopes K, et al. Presenilin 1 is required for maturation and cell surface accumulation of nicastrin. J Biol Chem. 2002;277:19236-40 pubmed
    ..Presenilins (PS1 and PS2) facilitate the final step in Abeta production, the intramembranous gamma-secretase cleavage of amyloid precursor ..
  44. Chan S, Culmsee C, Haughey N, Klapper W, Mattson M. Presenilin-1 mutations sensitize neurons to DNA damage-induced death by a mechanism involving perturbed calcium homeostasis and activation of calpains and caspase-12. Neurobiol Dis. 2002;11:2-19 pubmed
    ..Agents that release Ca(2+) from the ER increased the vulnerability of cells expressing mutant PS1 to DNA damage. By promoting ER-mediated apoptotic proteolytic cascades, PS1 mutations may sensitize neurons to DNA damage. ..
  45. Nyabi O, Bentahir M, Horré K, Herreman A, Gottardi Littell N, Van Broeckhoven C, et al. Presenilins mutated at Asp-257 or Asp-385 restore Pen-2 expression and Nicastrin glycosylation but remain catalytically inactive in the absence of wild type Presenilin. J Biol Chem. 2003;278:43430-6 pubmed
  46. Cras Méneur C, Li L, Kopan R, Permutt M. Presenilins, Notch dose control the fate of pancreatic endocrine progenitors during a narrow developmental window. Genes Dev. 2009;23:2088-101 pubmed publisher
  47. Ounallah Saad H, Beeri R, Goshen I, Yirmiya R, Renbaum P, Levy Lahad E. Transcriptional regulation of the murine Presenilin-2 gene reveals similarities and differences to its human orthologue. Gene. 2009;446:81-9 pubmed publisher
    ..The human Presenilin-2 (PSEN2) regulatory region includes two separate promoters modulated by Egr-1, a transcription factor involved in learning ..
  48. Kumar A, Thakur M. Presenilin 1 and 2 are expressed differentially in the cerebral cortex of mice during development. Neurochem Int. 2012;61:778-82 pubmed publisher
    Presenilin (PS) 1 and PS2 are multi-pass transmembrane proteins involved in vital brain functions. Studies using transgenic or conditional knockout models show that PS1 is implicated in crucial brain developmental processes...
  49. Blanchard V, Czech C, Bonici B, Clavel N, Gohin M, Dalet K, et al. Immunohistochemical analysis of presenilin 2 expression in the mouse brain: distribution pattern and co-localization with presenilin 1 protein. Brain Res. 1997;758:209-17 pubmed
    Missense mutations of presenilin 1 (PS-1) and presenilin 2 (PS-2) genes cause the majority of early-onset familial forms of Alzheimer's disease (AD)...
  50. Xia D, Watanabe H, Wu B, Lee S, Li Y, Tsvetkov E, et al. Presenilin-1 knockin mice reveal loss-of-function mechanism for familial Alzheimer's disease. Neuron. 2015;85:967-81 pubmed publisher
    ..Collectively, our findings reveal that FAD mutations can cause complete loss of Presenilin-1 function in vivo, suggesting that clinical PSEN mutations produce FAD through a loss-of-function mechanism. ..
  51. Zhang X, Garbett K, Veeraraghavalu K, Wilburn B, Gilmore R, Mirnics K, et al. A role for presenilins in autophagy revisited: normal acidification of lysosomes in cells lacking PSEN1 and PSEN2. J Neurosci. 2012;32:8633-48 pubmed publisher
    Presenilins 1 and 2 (PS1 and PS2) are the catalytic subunits of the ?-secretase complex, and genes encoding mutant PS1 and PS2 variants cause familial forms of Alzheimer's disease. Lee et al...
  52. Foveau B, Ancot F, Leroy C, Petrelli A, Reiss K, Vingtdeux V, et al. Down-regulation of the met receptor tyrosine kinase by presenilin-dependent regulated intramembrane proteolysis. Mol Biol Cell. 2009;20:2495-507 pubmed publisher
    ..This demonstrates the original involvement of a proteolytic process in degradation of the Met receptor implicated in negative regulation of invasive growth. ..
  53. Jayadev S, Case A, Eastman A, Nguyen H, Pollak J, Wiley J, et al. Presenilin 2 is the predominant ?-secretase in microglia and modulates cytokine release. PLoS ONE. 2010;5:e15743 pubmed publisher
    Presenilin 1 (PS1) and Presenilin 2 (PS2) are the enzymatic component of the ?-secretase complex that cleaves amyloid precursor protein (APP) to release amyloid beta (A?) peptide...
  54. Berechid B, Kitzmann M, Foltz D, Roach A, Seiffert D, Thompson L, et al. Identification and characterization of presenilin-independent Notch signaling. J Biol Chem. 2002;277:8154-65 pubmed
    ..Here we observe that a partial activation of the HES1 promoter can be detected in PS1/PS2 (PS1/2) double null cells using Notch1 Delta E constructs or following Delta 1 stimulation, despite an apparent ..
  55. Thakur M, Ghosh S. Age and sex dependent alteration in presenilin expression in mouse cerebral cortex. Cell Mol Neurobiol. 2007;27:1059-67 pubmed
    ..3) Our results demonstrate that PS1 was downregulated and PS 2 was upregulated in old mice of both sexes...
  56. Kaufmann M, Barth S, Konietzko U, Wu B, Egger S, Kunze R, et al. Dysregulation of hypoxia-inducible factor by presenilin/?-secretase loss-of-function mutations. J Neurosci. 2013;33:1915-26 pubmed publisher
    ..Together, our results suggest a direct role for PSEN in the regulation of the oxygen sensing pathway via the APP/AICD cleavage cascade. ..
  57. Pericak Vance M, Haines J. Genetic susceptibility to Alzheimer disease. Trends Genet. 1995;11:504-8 pubmed
    ..AD presents as a prototype of the power of genetic techniques in defining the etiology of a complex disease. ..
  58. Area Gomez E, de Groof A, Boldogh I, Bird T, Gibson G, Koehler C, et al. Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria. Am J Pathol. 2009;175:1810-6 pubmed publisher
    Presenilin-1 (PS1) and -2 (PS2), which when mutated cause familial Alzheimer disease, have been localized to numerous compartments of the cell, including the endoplasmic reticulum, Golgi, nuclear envelope, endosomes, lysosomes, the ..
  59. Demehri S, Liu Z, Lee J, Lin M, Crosby S, Roberts C, et al. Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity. PLoS Biol. 2008;6:e123 pubmed publisher
    ..These observations demonstrate that local skin perturbations can drive a lethal systemic disease and have important implications for a wide range of humoral and autoimmune diseases with skin manifestations. ..
  60. Tournoy J, Bossuyt X, Snellinx A, Regent M, Garmyn M, Serneels L, et al. Partial loss of presenilins causes seborrheic keratosis and autoimmune disease in mice. Hum Mol Genet. 2004;13:1321-31 pubmed
    Presenilin (PS1) and (PS2) are the centers of gamma-secretase that release Abeta from APP in Alzheimer's disease (AD). They cleave signaling proteins like Notch and downregulate beta-catenin to modulate Wnt signaling...
  61. Kirschenbaum F, Hsu S, Cordell B, McCarthy J. Substitution of a glycogen synthase kinase-3beta phosphorylation site in presenilin 1 separates presenilin function from beta-catenin signaling. J Biol Chem. 2001;276:7366-75 pubmed
    ..These results argue against a pathologically relevant role for the association between PS1 and beta-catenin in familial Alzheimer's disease. ..
  62. Bélanger V, Picard N, Cermakian N. The circadian regulation of Presenilin-2 gene expression. Chronobiol Int. 2006;23:747-66 pubmed
    ..These data indicate a unique mode of regulation of Presenilin-2 transcripts, the circadian control of which appears to happen at the transcriptional and post-transcriptional levels. ..
  63. Sevalle J, Ayral E, Hernandez J, Martinez J, Checler F. Pharmacological evidences for DFK167-sensitive presenilin-independent gamma-secretase-like activity. J Neurochem. 2009;110:275-83 pubmed publisher
    ..This activity is enhanced by PS1 and PS2 mutations known to be responsible for familial forms of AD and reduced by aspartyl mutations inactivating PS or in ..
  64. Suzuki Y, Ohta K, Itoh M, Sakoh Sumitomo Y, Mitsuda T, Ueda M, et al. An alternative spliced mouse presenilin-2 mRNA encodes a novel gamma-secretase inhibitor. FEBS Lett. 2009;583:1403-8 pubmed publisher
    The gamma-secretase, composed of presenilin-1 (PS1) or presenilin-2 (PS2), nicastrin (NCT), anterior pharynx-defective phenotype 1 (APH-1), and PEN-2, is critical for the development of Alzheimer's disease (AD)...
  65. Duplan E, Sevalle J, Viotti J, Goiran T, Bauer C, Renbaum P, et al. Parkin differently regulates presenilin-1 and presenilin-2 functions by direct control of their promoter transcription. J Mol Cell Biol. 2013;5:132-42 pubmed publisher
    ..Overall, our data delineate a promoter responsive element targeted by parkin that drives differential regulation of presenilin-1 and presenilin-2 transcription with functional consequences for ?-secretase activity and cell death. ..
  66. Yuk D, Lee Y, Nam S, Yun Y, Hwang D, Choi D, et al. Reduced anxiety in the mice expressing mutant (N141I) presenilin 2. J Neurosci Res. 2009;87:522-31 pubmed publisher
    Alzheimer's disease (AD) is characterized by progressive cognitive impairment. The effect of presenilin 1 (PS1) and PS2 mutation on cognition has been well characterized in a variety of transgenic mice...
  67. Boyle S, Liu Z, Kopan R. Notch signaling is required for the formation of mesangial cells from a stromal mesenchyme precursor during kidney development. Development. 2014;141:346-54 pubmed publisher
    ..Together, these data demonstrate a unique origin of mesangial cells and demonstrate a novel, redundant function for Notch receptors in mesangial cell specification, proliferation or survival during kidney development. ..
  68. Kumar A, Thakur M. Epigenetic regulation of presenilin 1 and 2 in the cerebral cortex of mice during development. Dev Neurobiol. 2015;75:1165-73 pubmed publisher
    ..Therefore, we have analyzed the epigenetic regulation of PS1 and PS2 in mouse cerebral cortex during development...