Psen1

Summary

Gene Symbol: Psen1
Description: presenilin 1
Alias: presenilin-1, PS-1
Species: rat
Products:     Psen1

Top Publications

  1. 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
    Mutations in two related genes, presenilin 1 and 2, account for most early-onset familial Alzheimer's disease. Although structural features indicate that the presenilins are membrane proteins, their function(s) is unknown...
  2. 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
    ..Using two highly specific antibodies against nonoverlapping epitopes of the PS1-encoded polypeptide, termed presenilin 1 (PS1), we document that the preponderant PS1-related species that accumulate in cultured mammalian cells, and ..
  3. 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. ..
  4. De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm J, et al. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature. 1999;398:518-22 pubmed
    ..Thus the targeting of gamma-secretase for the treatment of Alzheimer's disease may risk toxicity caused by reduced Notch signalling. ..
  5. 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. ..
  6. Pigino G, Morfini G, Pelsman A, Mattson M, Brady S, Busciglio J. Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport. J Neurosci. 2003;23:4499-508 pubmed
    ..Recent work indicates that presenilin 1 (PS1) interacts with glycogen synthase kinase 3beta (GSK3beta)...
  7. Wilson C, Murphy D, Giasson B, Zhang B, Trojanowski J, Lee V. Degradative organelles containing mislocalized alpha-and beta-synuclein proliferate in presenilin-1 null neurons. J Cell Biol. 2004;165:335-46 pubmed
  8. 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)...
  9. Kamal A, Almenar Queralt A, Leblanc J, Roberts E, Goldstein L. Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature. 2001;414:643-8 pubmed

More Information

Publications88

  1. Feng R, Rampon C, Tang Y, Shrom D, Jin J, Kyin M, et al. Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron. 2001;32:911-26 pubmed
    ..A chronic, abnormal clearance process in the hippocampus may conceivably lead to memory disorders in the mammalian brain. ..
  2. Takashima A, Murayama M, Murayama O, Kohno T, Honda T, Yasutake K, et al. Presenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau. Proc Natl Acad Sci U S A. 1998;95:9637-41 pubmed
    Families bearing mutations in the presenilin 1 (PS1) gene develop Alzheimer's disease. Previous studies have shown that the Alzheimer-associated mutations in PS1 increase production of amyloid beta protein (Abeta1-42)...
  3. 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...
  4. 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
    ..associated with autosomal dominant inheritance of mutations in genes encoding the amyloid precursor protein, presenilin 1 (PS1) and presenilin 2 (PS2)...
  5. Shen J, Bronson R, Chen D, Xia W, Selkoe D, Tonegawa S. Skeletal and CNS defects in Presenilin-1-deficient mice. Cell. 1997;89:629-39 pubmed
    ..5. These results show that PS1 is required for proper formation of the axial skeleton, normal neurogenesis, and neuronal survival. ..
  6. Pasternak S, Bagshaw R, Guiral M, Zhang S, Ackerley C, Pak B, et al. Presenilin-1, nicastrin, amyloid precursor protein, and gamma-secretase activity are co-localized in the lysosomal membrane. J Biol Chem. 2003;278:26687-94 pubmed
    ..These data reassert the importance of the lysosomal/endosomal system in the generation of Abeta and suggest a role for lysosomes in the pathophysiology of AD. ..
  7. Conboy L, Seymour C, Monopoli M, O Sullivan N, Murphy K, Regan C. Notch signalling becomes transiently attenuated during long-term memory consolidation in adult Wistar rats. Neurobiol Learn Mem. 2007;88:342-51 pubmed
    ..As down-regulation of Notch signalling promotes differentiation and neurite outgrowth in post-mitotic neurons, it is proposed that this pathway regulates the integration of synapses transiently produced during memory consolidation. ..
  8. Yuasa S, Nakajima M, Aizawa H, Sahara N, Koizumi K, Sakai T, et al. Impaired cell cycle control of neuronal precursor cells in the neocortical primordium of presenilin-1-deficient mice. J Neurosci Res. 2002;70:501-13 pubmed
    ..These findings suggest that PS-1 is involved in the differentiation and the cell cycle control of neuronal precursor cells in the ventricular proliferating zone of the neocortical primordium. ..
  9. 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
    ..The distinct yet overlapping enzymatic properties of the PS1 gamma-secretase complex and the PS2 gamma-secretase complex imply that these two putative aspartyl class proteases may contribute to different biological processes. ..
  10. Imafuku I, Masaki T, Waragai M, Takeuchi S, Kawabata M, Hirai S, et al. Presenilin 1 suppresses the function of c-Jun homodimers via interaction with QM/Jif-1. J Cell Biol. 1999;147:121-34 pubmed
    b>Presenilin 1 (PS1) is the causative gene for an autosomal dominant familial Alzheimer's disease (AD) mapped to chromosome 14...
  11. 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. ..
  12. Li T, Wen H, Brayton C, Laird F, Ma G, Peng S, et al. Moderate reduction of gamma-secretase attenuates amyloid burden and limits mechanism-based liabilities. J Neurosci. 2007;27:10849-59 pubmed
    ..Our findings suggest that moderate inhibition of gamma-secretase represents an attractive anti-amyloid therapy for Alzheimer's disease. ..
  13. Mizuguchi R, Kriks S, Cordes R, Gossler A, Ma Q, Goulding M. Ascl1 and Gsh1/2 control inhibitory and excitatory cell fate in spinal sensory interneurons. Nat Neurosci. 2006;9:770-8 pubmed
    ..We propose that this switch in Ascl1 function enables the cogeneration of inhibitory and excitatory sensory interneurons from a common pool of dorsal progenitors. ..
  14. Kaufman A, Salazar S, Haas L, Yang J, Kostylev M, Jeng A, et al. Fyn inhibition rescues established memory and synapse loss in Alzheimer mice. Ann Neurol. 2015;77:953-71 pubmed publisher
    ..Targeting Fyn can reverse memory deficits found in AD mouse models, and rescue synapse density loss characteristic of the disease. Thus, AZD0530 is a promising candidate to test as a potential therapy for AD. ..
  15. Kim J, Hamamoto S, Ravazzola M, Orci L, Schekman R. Uncoupled packaging of amyloid precursor protein and presenilin 1 into coat protein complex II vesicles. J Biol Chem. 2005;280:7758-68 pubmed
    ..Titration of Sarla distinguished the packaging requirements of APP and PS1. Furthermore, APP packaging was not affected by deletion of PS1 or PS1 and 2, suggesting APP and PS1 trafficking from the ER are normally uncoupled...
  16. 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. ..
  17. 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
    ..These results establish a critical role of PS in myelopoiesis. Our finding that this activity can be directly modulated by its gamma-secretase activity has important safety implications concerning these inhibitors. ..
  18. Chen F, Tandon A, Sanjo N, Gu Y, Hasegawa H, Arawaka S, et al. Presenilin 1 and presenilin 2 have differential effects on the stability and maturation of nicastrin in Mammalian brain. J Biol Chem. 2003;278:19974-9 pubmed
    ..Absence of presenilin 1 (PS1) is associated with dramatic reductions in the level of mature glycosylated nicastrin and with ..
  19. Lee S, Shah S, Li H, Yu C, Han W, Yu G. Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch. J Biol Chem. 2002;277:45013-9 pubmed
    ..These data indicate that mAPH-1 is probably a functional component of the gamma-secretase complex required for the intramembrane proteolysis of APP and Notch. ..
  20. Li Y, Lai M, Xu M, Huang Q, DiMuzio Mower J, Sardana M, et al. Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state. Proc Natl Acad Sci U S A. 2000;97:6138-43 pubmed
    ..Upon gel exclusion chromatography, solubilized gamma-secretase activity coelutes with presenilin 1 (PS1) at an apparent relative molecular weight of approximately 2.0 x 10(6)...
  21. Ankarcrona M, Hultenby K. Presenilin-1 is located in rat mitochondria. Biochem Biophys Res Commun. 2002;295:766-70 pubmed
    ..The function of PS1 in mitochondrial membranes is presently unknown. PS1 mutations may make cells more vulnerable to apoptotic stimuli due to dysfunction of this protein at the mitochondrial level. ..
  22. Zhou Y, Zhang W, Easton R, Ray J, Lampe P, Jiang Z, et al. Presenilin-1 protects against neuronal apoptosis caused by its interacting protein PAG. Neurobiol Dis. 2002;9:126-38 pubmed
  23. Amson R, Lassalle J, Halley H, Prieur S, Lethrosne F, Roperch J, et al. Behavioral alterations associated with apoptosis and down-regulation of presenilin 1 in the brains of p53-deficient mice. Proc Natl Acad Sci U S A. 2000;97:5346-50 pubmed
    b>Presenilin 1 (PS1) expression is repressed by the p53 tumor suppressor. As shown herein, wild-type PS1 is an effective antiapoptotic molecule capable of significantly inhibiting p53-dependent and p53-independent cell death...
  24. Satpathy A, Briseño C, Lee J, Ng D, Manieri N, Kc W, et al. Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat Immunol. 2013;14:937-48 pubmed publisher
    ..rodentium, but CD103(+) cDCs dependent on the transcription factor Batf3 were not. Our results demonstrate a nonredundant function for CD11b(+) cDCs in the response to pathogens in vivo. ..
  25. 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
    The majority of cases with early onset familial Alzheimer's disease have been attributed to mutations in the presenilin 1 (PS1) gene...
  26. Elzinga B, Twomey C, Powell J, Harte F, McCarthy J. Interleukin-1 receptor type 1 is a substrate for gamma-secretase-dependent regulated intramembrane proteolysis. J Biol Chem. 2009;284:1394-409 pubmed publisher
    ..These findings also suggest that regulated intramembrane proteolysis may be a control mechanism for IL-1R1-mediated signaling. ..
  27. 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
  28. Kong Y, Yao L, Lu C, Sun Y, Ni J. [Effects of vitamin E on expression of PS-1 and production of Abeta in the hippocampus of female senile rats]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2007;23:237-40 pubmed
    ..Neurons were gradually recovered in VE groups. VE may depress the production of Abeta by regulating the expression of PS-1, reducing neuronal injuries. VE may play a role in neuronal protection. ..
  29. Gowrishankar K, Zeidler M, Vincenz C. Release of a membrane-bound death domain by gamma-secretase processing of the p75NTR homolog NRADD. J Cell Sci. 2004;117:4099-111 pubmed
    ..Our results demonstrate that NRADD is an additional gamma-secretase substrate and suggest that drugs against Alzheimer's disease will need to target gamma-secretase in a substrate-specific manner. ..
  30. 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. ..
  31. Marambaud P, Shioi J, Serban G, Georgakopoulos A, Sarner S, Nagy V, et al. A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J. 2002;21:1948-56 pubmed
    ..Thus, the PS1/gamma-secretase system stimulates disassembly of the E-cadherin- catenin complex and increases the cytosolic pool of beta-catenin, a key regulator of the Wnt signaling pathway. ..
  32. Sakuma K, Nakao R, Yamasa Y, Yasuhara M. Normal distribution of presenilin-1 and nicastrin in skeletal muscle and the differential responses of these proteins after denervation. Biochim Biophys Acta. 2006;1760:980-7 pubmed
    ..These data suggest that enhanced presenilin-1 protein may play a role in the degeneration and regeneration of skeletal muscle. ..
  33. Mitsuishi Y, Hasegawa H, Matsuo A, Araki W, Suzuki T, Tagami S, et al. Human CRB2 inhibits gamma-secretase cleavage of amyloid precursor protein by binding to the presenilin complex. J Biol Chem. 2010;285:14920-31 pubmed publisher
    ..Our results suggest that CRB2 functions as an inhibitory binding protein that is involved in the formation of a mature but inactive pool of the gamma-secretase complex. ..
  34. Kanekiyo T, Liu C, Shinohara M, Li J, Bu G. LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-?. J Neurosci. 2012;32:16458-65 pubmed publisher
    ..These studies establish critical functions of the cerebrovasculature system in A? metabolism and identify a new pathway involved in the pathogenesis of both AD and CAA. ..
  35. Westerman M, Cooper Blacketer D, Mariash A, Kotilinek L, Kawarabayashi T, Younkin L, et al. The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's disease. J Neurosci. 2002;22:1858-67 pubmed
    ..These studies also provide a methodological framework within which to investigate these Abeta assemblies in vivo. ..
  36. Handler M, Yang X, Shen J. Presenilin-1 regulates neuronal differentiation during neurogenesis. Development. 2000;127:2593-606 pubmed
    ..1997, Nature 387, 288-292). These results provide direct evidence that PS1 controls neuronal differentiation in association with the downregulation of Notch signalling during neurogenesis. ..
  37. Kocki J, Ułamek Kozioł M, Bogucka Kocka A, Januszewski S, Jabłoński M, Gil Kulik P, et al. Dysregulation of Amyloid-β Protein Precursor, β-Secretase, Presenilin 1 and 2 Genes in the Rat Selectively Vulnerable CA1 Subfield of Hippocampus Following Transient Global Brain Ischemia. J Alzheimers Dis. 2015;47:1047-56 pubmed publisher
    ..Our data demonstrate that brain ischemia activates delayed neuronal death in hippocampus in an AβPP-dependent manner, thus defining a new and important mode of ischemic cell death. ..
  38. Herms J, Schneider I, Dewachter I, Caluwaerts N, Kretzschmar H, Van Leuven F. Capacitive calcium entry is directly attenuated by mutant presenilin-1, independent of the expression of the amyloid precursor protein. J Biol Chem. 2003;278:2484-9 pubmed
  39. Zacharek A, Chen J, Cui X, Yang Y, Chopp M. Simvastatin increases notch signaling activity and promotes arteriogenesis after stroke. Stroke. 2009;40:254-60 pubmed publisher
    Notch signaling activity regulates arteriogenesis. Presenilin 1 (PS1) mediates Notch signaling activity via cleavage of Notch, liberating Notch intracellular domain (NICD)...
  40. Nakajima M, Moriizumi E, Koseki H, Shirasawa T. Presenilin 1 is essential for cardiac morphogenesis. Dev Dyn. 2004;230:795-9 pubmed
    b>Presenilin 1 (PS1) is the gene responsible for the development of early-onset familial Alzheimer's disease. PS1-deficient mice have been reported to show defects in neurogenesis, somitogenesis and angiogenesis...
  41. 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. ..
  42. Hansson C, Frykman S, Farmery M, Tjernberg L, Nilsberth C, Pursglove S, et al. Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria. J Biol Chem. 2004;279:51654-60 pubmed
    ..We previously reported that presenilin 1 (PS1), which is often mutated in familial forms of Alzheimer's disease, is located in mitochondria and ..
  43. 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. ..
  44. Tu H, Nelson O, Bezprozvanny A, Wang Z, Lee S, Hao Y, et al. Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations. Cell. 2006;126:981-93 pubmed
    ..The ER Ca(2+) leak function of presenilins is independent of their gamma-secretase activity. Our data suggest a Ca(2+) signaling function for presenilins and provide support for the "Ca(2+) hypothesis of AD." ..
  45. Yang Y, Kinney G, Spain W, Breitner J, Cook D. Presenilin-1 and intracellular calcium stores regulate neuronal glutamate uptake. J Neurochem. 2004;88:1361-72 pubmed
    ..Taken together, these findings indicate that PS1 and intracellular calcium stores may play a significant role in regulating glutamate uptake and therefore may be important in limiting glutamate toxicity in the brain. ..
  46. Guo Q, Sebastian L, Sopher B, Miller M, Glazner G, Ware C, et al. Neurotrophic factors [activity-dependent neurotrophic factor (ADNF) and basic fibroblast growth factor (bFGF)] interrupt excitotoxic neurodegenerative cascades promoted by a PS1 mutation. Proc Natl Acad Sci U S A. 1999;96:4125-30 pubmed
    ..Our data indicate that neurotrophic factors can interrupt excitotoxic neurodegenerative cascades promoted by PS1 mutations. ..
  47. Kim T, Vidal G, Djurisic M, William C, Birnbaum M, Garcia K, et al. Human LilrB2 is a ?-amyloid receptor and its murine homolog PirB regulates synaptic plasticity in an Alzheimer's model. Science. 2013;341:1399-404 pubmed publisher
    ..These findings imply that LilrB2 contributes to human AD neuropathology and suggest therapeutic uses of blocking LilrB2 function. ..
  48. 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. ..
  49. Tung Y, Wang B, Hsu W, Hu M, Her G, Huang W, et al. Presenilin-1 regulates the expression of p62 to govern p62-dependent tau degradation. Mol Neurobiol. 2014;49:10-27 pubmed publisher
    ..Our study suggests a novel function for PS1 in modulating p62 expression to control the proteostasis of Tau. ..
  50. Morton R, Kuenzi F, Fitzjohn S, Rosahl T, Smith D, Zheng H, et al. Impairment in hippocampal long-term potentiation in mice under-expressing the Alzheimer's disease related gene presenilin-1. Neurosci Lett. 2002;319:37-40 pubmed
    ..These results demonstrate that chronic reduction of PS1 activity leads to impaired synaptic plasticity, thus suggesting a role for PS1 in normal cognitive function. ..
  51. St George Hyslop P, Levesque G, Levesque L, Rommens J, Westaway D, Fraser P. Two homologous genes causing early-onset familial Alzheimer's disease. Cold Spring Harb Symp Quant Biol. 1996;61:559-64 pubmed
  52. Mattson M, Zhu H, Yu J, Kindy M. Presenilin-1 mutation increases neuronal vulnerability to focal ischemia in vivo and to hypoxia and glucose deprivation in cell culture: involvement of perturbed calcium homeostasis. J Neurosci. 2000;20:1358-64 pubmed
    ..The data further suggest that drugs that stabilize endoplasmic reticulum calcium homeostasis may prove effective in suppressing the neurodegenerative process in AD patients...
  53. Matrone C, Marolda R, Ciafre S, Ciotti M, Mercanti D, Calissano P. Tyrosine kinase nerve growth factor receptor switches from prosurvival to proapoptotic activity via Abeta-mediated phosphorylation. Proc Natl Acad Sci U S A. 2009;106:11358-63 pubmed publisher
  54. Yang J, Li T. The ciliary rootlet interacts with kinesin light chains and may provide a scaffold for kinesin-1 vesicular cargos. Exp Cell Res. 2005;309:379-89 pubmed
    ..Additionally, amyloid precursor protein (APP; a kinesin-1 vesicular cargo receptor) and presenilin 1 (a presumed cargo of APP/kinesin-1) were found to be enriched along the rootletin fibers, suggesting that the ..
  55. Kilb W, Hartmann D, Saftig P, Luhmann H. Altered morphological and electrophysiological properties of Cajal-Retzius cells in cerebral cortex of embryonic Presenilin-1 knockout mice. Eur J Neurosci. 2004;20:2749-56 pubmed
    ..The depolarized membrane potential observed in PS1-/- CRcs may increase the susceptibility to neuronal death, thus facilitating the premature loss of CRcs in PS1-/- mice. ..
  56. Bai X, Yan C, Yang G, Lu P, Ma D, Sun L, et al. An atomic structure of human γ-secretase. Nature. 2015;525:212-217 pubmed publisher
    ..Alzheimer's disease, with most mutations derived from Alzheimer's disease mapping to the catalytic subunit presenilin 1 (PS1). Here we report an atomic structure of human γ-secretase at 3...
  57. Viswanathan J, Haapasalo A, Böttcher C, Miettinen R, Kurkinen K, Lu A, et al. Alzheimer's disease-associated ubiquilin-1 regulates presenilin-1 accumulation and aggresome formation. Traffic. 2011;12:330-48 pubmed publisher
    ..Collectively, our results indicate that specific ubiquilin-1 TVs can cause PS1 accumulation and aggresome formation, which may impact AD pathogenesis or susceptibility. ..
  58. Kobayashi S, Sasaki T, Katayama T, Hasegawa T, Nagano A, Sato K. Temporal-spatial expression of presenilin 1 and the production of amyloid-beta after acute spinal cord injury in adult rat. Neurochem Int. 2010;56:387-93 pubmed publisher
    ..b>Presenilin 1 (PS1) is the catalytic subunit of gamma-secretase and PS1 mutations cause Alzheimer's disease, spastic ..
  59. 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
    ..different 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...
  60. Six E, Ndiaye D, Laabi Y, Brou C, Gupta Rossi N, Israel A, et al. The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and gamma-secretase. Proc Natl Acad Sci U S A. 2003;100:7638-43 pubmed
    ..Therefore Dll1 is a substrate for regulated intramembrane proteolysis, and its intracellular region possibly fulfills a specific function in the nucleus. ..
  61. Vetrivel K, Cheng H, Kim S, Chen Y, Barnes N, Parent A, et al. Spatial segregation of gamma-secretase and substrates in distinct membrane domains. J Biol Chem. 2005;280:25892-900 pubmed
  62. Xu X, Shi Y, Wu X, Gambetti P, Sui D, Cui M. Identification of a novel PSD-95/Dlg/ZO-1 (PDZ)-like protein interacting with the C terminus of presenilin-1. J Biol Chem. 1999;274:32543-6 pubmed
    ..These data suggest that PS-1 may associate with a PDZ-like domain-containing protein in vivo and thus may participate in receptor or channel clustering and intracellular signaling events in the brain. ..
  63. Tong B, Lee C, Cheng W, Lai K, Foskett J, Cheung K. Familial Alzheimer's disease-associated presenilin 1 mutants promote γ-secretase cleavage of STIM1 to impair store-operated Ca2+ entry. Sci Signal. 2016;9:ra89 pubmed publisher
    ..Our results indicate that γ-secretase activity may physiologically regulate CCE by targeting STIM1 and that restoring STIM1 may be a therapeutic approach in AD. ..
  64. Hartmann D, De Strooper B, Saftig P. Presenilin-1 deficiency leads to loss of Cajal-Retzius neurons and cortical dysplasia similar to human type 2 lissencephaly. Curr Biol. 1999;9:719-27 pubmed
  65. Jung C, Fuhrmann M, Honarnejad K, Van Leuven F, Herms J. Role of presenilin 1 in structural plasticity of cortical dendritic spines in vivo. J Neurochem. 2011;119:1064-73 pubmed publisher
    ..In consequence, our results favor the view that PS1 influences dendritic spine plasticity in a gain-of-function but ?-secretase-independent manner. ..
  66. Jung M, Metzger D, Das H. The Role of Presenilin-1 in the Excitotoxicity of Ethanol Withdrawal. J Pharmacol Exp Ther. 2016;358:516-26 pubmed publisher
    ..DAPT attenuated the toxic effect of EW or glutamate on HT22 cells. These results suggest that PS1 expression is triggered by glutamate through p38?, contributing to the excitotoxic stimulus of EW. ..
  67. Baki L, Shioi J, Wen P, Shao Z, Schwarzman A, Gama Sosa M, et al. PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations. EMBO J. 2004;23:2586-96 pubmed
    ..Our data raise the possibility that PS1 may prevent development of AD pathology by activating the PI3K/Akt signaling pathway. In contrast, FAD mutations may promote AD pathology by inhibiting this pathway. ..
  68. Gil C, Cubi R, Aguilera J. Shedding of the p75NTR neurotrophin receptor is modulated by lipid rafts. FEBS Lett. 2007;581:1851-8 pubmed
    ..In summary, our results point to a role of lipid rafts in the modulation of the shedding of the p75(NTR) receptor. ..
  69. Nelson O, Tu H, Lei T, Bentahir M, De Strooper B, Bezprozvanny I. Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1. J Clin Invest. 2007;117:1230-9 pubmed
    ..Our observations are consistent with the potential role of disturbed Ca(2+) homeostasis in Alzheimer disease pathogenesis. ..
  70. Um J, Kaufman A, Kostylev M, Heiss J, Stagi M, Takahashi H, et al. Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer a? oligomer bound to cellular prion protein. Neuron. 2013;79:887-902 pubmed publisher
    ..For mice expressing familial AD transgenes, mGluR5 antagonism reverses deficits in learning, memory, and synapse density. Thus, A?o-PrP(C) complexes at the neuronal surface activate mGluR5 to disrupt neuronal function. ..
  71. Fiuza U, Arias A. Cell and molecular biology of Notch. J Endocrinol. 2007;194:459-74 pubmed
    ..In this review, we will describe the multiple roles of Notch and how various factors can regulate Notch signalling...
  72. Esselens C, Oorschot V, Baert V, Raemaekers T, Spittaels K, Serneels L, et al. Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway. J Cell Biol. 2004;166:1041-54 pubmed
    b>Presenilin 1 (PS1) interacts with telencephalin (TLN) and the amyloid precursor protein via their transmembrane domain (Annaert, W.G., C. Esselens, V. Baert, C. Boeve, G. Snellings, P. Cupers, K. Craessaerts, and B. De Strooper. 2001...
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    ..Furthermore, Elk-1 transcription activity also down-regulates in PS1(-/-) MEF cells. Collectively, our data suggest that PS can modulate the basal level of ERK activity through the Raf-MEK-dependent pathway. ..
  74. Mohmmad Abdul H, Sultana R, Keller J, St Clair D, Markesbery W, Butterfield D. Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications. J Neurochem. 2006;96:1322-35 pubmed
    ..The results are consonant with the hypothesis that Abeta(1-42)-associated oxidative stress and increased vulnerability to oxidative stress may contribute significantly to neuronal apoptosis and death in familial early onset AD. ..
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  76. Payette D, Xie J, Guo Q. Reduction in CHT1-mediated choline uptake in primary neurons from presenilin-1 M146V mutant knock-in mice. Brain Res. 2007;1135:12-21 pubmed
    ..Since human neocortex has recently been shown to possess intrinsic cholinergic innervation, our results indicate that alterations in CHT1-mediated high affinity choline uptake in cortical neurons may contribute to Alzheimer's dementia...
  77. Xiong K, Clough R, Luo X, Struble R, Li Y, Yan X. [3H]-L-685,458 as a radiotracer that maps gamma-secretase complex in the rat brain: relevance to Abeta genesis and presence of active presenilin-1 components. Brain Res. 2007;1157:81-91 pubmed
    ..Together, [3H]-L-685,458 is an excellent radiotracer for mapping active gamma-secretase complex, and may serve as a useful tool for studying the enzyme in vivo and in vitro. ..
  78. Kim J, Castellano J, Jiang H, Basak J, Parsadanian M, Pham V, et al. Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance. Neuron. 2009;64:632-44 pubmed publisher
    ..Plaque-associated neuroinflammatory responses were attenuated in LDLR transgenic mice. These findings suggest that increasing LDLR levels may represent a novel AD treatment strategy. ..
  79. Laky K, Fowlkes B. Presenilins regulate alphabeta T cell development by modulating TCR signaling. J Exp Med. 2007;204:2115-29 pubmed