PSEN2

Summary

Gene Symbol: PSEN2
Description: presenilin 2 (Alzheimer disease 4)
Summary: Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1 or PSEN2) or the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor such that, they either directly regulate gamma-secretase activity, or themselves act are protease enzymes. Two alternatively spliced transcript variants encoding different isoforms of PSEN2 have been identified. [provided by RefSeq]
Alias: AD3L, AD4, PS2, STM2, AD3LP, AD5, Alzheimer's disease 3-like, E5-1, OTTHUMP00000035672, PS-2, STM-2, presenilin-2
Species: human

Webpages

  1. robert w. doms, phd
    www.med.upenn.edu/ins/faculty/doms.htm
  2. ncur poster 1996
    www.bio.davidson.edu/Biology/student/NCUR96.html

Publications

  1. Transcriptional regulation of the human FTZ-F1 gene encoding Ad4BP/SF-1
    K Oba
    The Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi Higashi-ku, Fukuoka 812-8582, Japan
    J Biochem 128:517-28
  2. Genes and mechanisms involved in beta-amyloid generation and Alzheimer's disease
    H Steiner
    Adolf-Butenandt-Institute, Ludwig-Maximilians-University, Dept. of Biochemistry, Munich, Germany
    Eur Arch Psychiatry Clin Neurosci 249:266-70
  3. The function of presenilin-1 in amyloid beta-peptide generation and brain development
    P Saftig
    Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universität Göttingen, Germany
    Eur Arch Psychiatry Clin Neurosci 249:271-9
  4. Expression of the breast cancer-associated protein pS2 in adenosquamous carcinomas of the gastrointestinal tract
    C Welter
    Institut für Humangenetik, Universität des Saarlandes, Homburg/Saar, Germany
    Acta Oncol 32:315-7
  5. A novel mutation in the PSEN2 gene (T430M) associated with variable expression in a family with early-onset Alzheimer disease
    Mario Ezquerra
    Genetics Service, Department of Ciencias Fisiologicas I, University of Barcelona, Institut de Investigacions Biomédiques Agustí Pi i Sunyer, Hospital Clínic, Villaroel 170, 08036 Barcelona, Spain
    Arch Neurol 60:1149-51
  6. Molecular genetics of Alzheimer's disease: presenilin 1 gene analysis in a cohort of patients from the Poznań region
    Anna Kowalska
    Institute of Human Genetics, Polish Academy of Sciences, ul Strzeszyńska 32, 60 479 Poznań
    J Appl Genet 44:231-4
  7. Absence of association between Alzheimer disease and the regulatory region polymorphism of the PS2 gene in an Italian population
    Manuela Di Natale
    Centro Regionale di Neurogenetica AS 6, Viale A Perugini, 88046, Lamezia Terme CZ, Italy
    Neurosci Lett 343:210-2
  8. The C-terminal fragment of presenilin 2 triggers p53-mediated staurosporine-induced apoptosis, a function independent of the presenilinase-derived N-terminal counterpart
    Cristine Alves da Costa
    Intitut de Pharmacologie Moléculaire et Cellulaire of CNRS, UMR6097, Valbonne 06560, France
    J Biol Chem 278:12064-9
  9. Transcriptional synergism on the pS2 gene promoter between a p160 coactivator and estrogen receptor-alpha depends on the coactivator subtype, the type of estrogen response element, and the promoter context
    Tomas Barkhem
    Karo Bio AB, Novum, S 141 57 Huddinge, Sweden
    Mol Endocrinol 16:2571-81
  10. Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch
    Sheu Fen Lee
    Center for Basic Neuroscience and Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9111, USA
    J Biol Chem 277:45013-9

Scientific Experts

Detail Information

Publications67

  1. Transcriptional regulation of the human FTZ-F1 gene encoding Ad4BP/SF-1
    K Oba
    The Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi Higashi-ku, Fukuoka 812-8582, Japan
    J Biochem 128:517-28
    ..FTZ-F1 genes, and a possible autoregulatory mechanism of the rFTZ-F1 gene by Ad4BP itself through binding to the Ad4 (or SF-1) site in the first intron...
  2. Genes and mechanisms involved in beta-amyloid generation and Alzheimer's disease
    H Steiner
    Adolf-Butenandt-Institute, Ludwig-Maximilians-University, Dept. of Biochemistry, Munich, Germany
    Eur Arch Psychiatry Clin Neurosci 249:266-70
    ..Like the mutations identified within the betaAPP gene, mutations in PS1 and PS2 cause the increased generation of Abeta42...
  3. The function of presenilin-1 in amyloid beta-peptide generation and brain development
    P Saftig
    Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universität Göttingen, Germany
    Eur Arch Psychiatry Clin Neurosci 249:271-9
    ..All mutations in the three FAD genes, i.e., amyloid precursor protein (APP), presenilin 1 (PS-1), and presenilin 2 (PS-2) cause an increased production of a longer, more amyloidogenic form of the amyloid peptide corroborating ..
  4. Expression of the breast cancer-associated protein pS2 in adenosquamous carcinomas of the gastrointestinal tract
    C Welter
    Institut für Humangenetik, Universität des Saarlandes, Homburg/Saar, Germany
    Acta Oncol 32:315-7
    The breast cancer-associated protein pS2 is also present in many human gastrointestinal tumors...
  5. A novel mutation in the PSEN2 gene (T430M) associated with variable expression in a family with early-onset Alzheimer disease
    Mario Ezquerra
    Genetics Service, Department of Ciencias Fisiologicas I, University of Barcelona, Institut de Investigacions Biomédiques Agustí Pi i Sunyer, Hospital Clínic, Villaroel 170, 08036 Barcelona, Spain
    Arch Neurol 60:1149-51
    ..associated with mutations in 3 different genes: the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes...
  6. Molecular genetics of Alzheimer's disease: presenilin 1 gene analysis in a cohort of patients from the Poznań region
    Anna Kowalska
    Institute of Human Genetics, Polish Academy of Sciences, ul Strzeszyńska 32, 60 479 Poznań
    J Appl Genet 44:231-4
    ..To date, some missense mutations in three genes encoding the amyloid precursor protein, presenilin 1 (PS1) and 2 (PS2) have been found to cause familial EOAD...
  7. Absence of association between Alzheimer disease and the regulatory region polymorphism of the PS2 gene in an Italian population
    Manuela Di Natale
    Centro Regionale di Neurogenetica AS 6, Viale A Perugini, 88046, Lamezia Terme CZ, Italy
    Neurosci Lett 343:210-2
    ..A recent study demonstrated that the deletion of adenosine in the promoter region of the presenilin 2 gene (PS2) is a susceptibility factor for early-onset AD...
  8. The C-terminal fragment of presenilin 2 triggers p53-mediated staurosporine-induced apoptosis, a function independent of the presenilinase-derived N-terminal counterpart
    Cristine Alves da Costa
    Intitut de Pharmacologie Moléculaire et Cellulaire of CNRS, UMR6097, Valbonne 06560, France
    J Biol Chem 278:12064-9
    ..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 ..
  9. Transcriptional synergism on the pS2 gene promoter between a p160 coactivator and estrogen receptor-alpha depends on the coactivator subtype, the type of estrogen response element, and the promoter context
    Tomas Barkhem
    Karo Bio AB, Novum, S 141 57 Huddinge, Sweden
    Mol Endocrinol 16:2571-81
    The pS2 gene is estrogen responsive in hepatocarcinoma cells (HepG2) in the presence of estrogen receptor alpha (ERalpha)...
  10. Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch
    Sheu Fen Lee
    Center for Basic Neuroscience and Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9111, USA
    J Biol Chem 277:45013-9
    ..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...
  11. Evaluation of multiple presenilin 2 SNPs for association with early-onset sporadic Alzheimer disease
    W Mathias Howell
    Center for Genomics and Bioinformatics, Karolinska Institute, Stockholm, Sweden
    Am J Med Genet 111:157-63
    ..Previously reported association studies of presenilin 2 (PSEN2) polymorphisms with early-onset Alzheimer disease (EOAD) have produced contradictory results...
  12. PEN-2 is an integral component of the gamma-secretase complex required for coordinated expression of presenilin and nicastrin
    Harald Steiner
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Schillerstrasse 44, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 277:39062-5
    ..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...
  13. Regulation of APP-dependent transcription complexes by Mint/X11s: differential functions of Mint isoforms
    Thomas Biederer
    The Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas Texas 75390 9111, USA
    J Neurosci 22:7340-51
    ..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...
  14. N141I mutant presenilin-2 gene enhances neuronal cell death and decreases bcl-2 expression
    Masaki Mori
    Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, 2 2 Yamada oka, Suita 565 0871, Japan
    Life Sci 70:2567-80
    ..Our study demonstrated that mutant PS-2 induces apoptosis accompanied by increased caspase-3-like activity and decreased bcl-2 expression in neuronal cells after serum-deprivation...
  15. A new splice variant of glial fibrillary acidic protein, GFAP epsilon, interacts with the presenilin proteins
    Anders Lade Nielsen
    Department of Human Genetics, University of Aarhus, Denmark
    J Biol Chem 277:29983-91
    ..Mutations in GFAP and presenilins are associated with Alexander disease and Alzheimer's disease, respectively. Accordingly, GFAP epsilon should be taken into consideration when studying neurodegenerative diseases...
  16. Impas 1 possesses endoproteolytic activity against multipass membrane protein substrate cleaving the presenilin 1 holoprotein
    Yuri K Moliaka
    University of Massachusetts Medical School, Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, 303 Belmont Street, Worcester, MA 01604, USA
    FEBS Lett 557:185-92
    Presenilins (PS1 and PS2) are supposed to be unusual aspartic proteases and components of the gamma-secretase complex regulating cleavage of type I proteins...
  17. The presenilin 2 M239I mutation associated with familial Alzheimer's disease reduces Ca2+ release from intracellular stores
    Giancarlo Zatti
    Department of Biomedical Sciences, University of Padova, Italy
    Neurobiol Dis 15:269-78
    ..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 ..
  18. The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone
    Christopher C Williams
    Department of Biochemistry, Tulane University Health Sciences Center, Tulane Cancer Center, New Orleans, LA 70112, USA
    J Cell Biol 167:469-78
    ..Subsequent binding of the two proteins at transcription factor target promoters results in activation of gene expression...
  19. Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP
    Rita Joao Guerreiro
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
    Neurobiol Aging 31:725-31
    ..Interestingly, in the latter series, we found five new non-synonymous changes in all three genes and a presenilin 2 variant (R62H) that has been previously related to AD...
  20. Tumor-associated neoexpression of the pS2 peptide and MUC5AC mucin in primary adenocarcinomas and signet ring cell carcinomas of the urinary bladder
    E Kunze
    Department of Osteopathology and Hematopathology, Center of Pathology, University of Göttingen, Germany
    Histol Histopathol 23:539-48
    ..analyzed by immunohistochemistry the expression of a broad panel of proteins, associated with cell differentiation (pS2 peptide, MUC5AC, MUC6, spasmolytic polypeptide, cyclooxygenases-1 and -2, caveolin-1), and of various novel known ..
  21. Two polymorphisms of presenilin-2 gene (PSEN2) 5' regulatory region are not associated with Alzheimer's disease (AD) in the Polish population
    M Gacia
    Medical Research Center, Department of Neurodegenerative Disorders, Polish Academy of Sciences, Warszawa, Poland
    J Neural Transm 115:85-90
    b>Presenilin 2 gene (PSEN2) is one of the causative genes for familial Alzheimer's disease. A delA polymorphism located in PSEN2 promoter was proposed to be a risk factor for early-onset AD...
  22. HMGA1a: sequence-specific RNA-binding factor causing sporadic Alzheimer's disease-linked exon skipping of presenilin-2 pre-mRNA
    Takayuki Manabe
    Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565 0871, Japan
    Genes Cells 12:1179-91
    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...
  23. The association of the regulatory region of the presenilin-2 gene with Alzheimer's disease in the Northern Han Chinese population
    Zheng Liu
    Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China
    J Neurol Sci 264:38-42
    ..Polymorphism of the promoter region of the presenilin-2 gene (PSEN2) has recently been reported in a Russian population to be associated with sporadic Alzheimer's disease (SAD)...
  24. Pathological activity of familial Alzheimer's disease-associated mutant presenilin can be executed by six different gamma-secretase complexes
    Keiro Shirotani
    Munich Center for Integrated Protein Science and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, Schillerstr 44, Munich, Germany
    Neurobiol Dis 27:102-7
    ..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...
  25. PEN-2 overexpression induces gamma-secretase protein and its activity with amyloid beta-42 production
    Su J Seo
    Division of Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA, 5 Nokbun dong Eunpyng ku, Seoul, Korea
    Neurochem Res 32:1016-23
    ..This cell line was also co-transfected with a combination of human mutant presenilin 2 (hPS2m) and APPsw...
  26. Changes in cholesterol metabolism are associated with PS1 and PS2 gene regulation in SK-N-BE
    A Crestini
    Department of Cellular Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy
    J Mol Neurosci 30:311-22
    ..The abundance of mRNA transcripts for presenilin 1 and 2 (PS1 and PS2), APP, and nicastrin were evaluated in neuroblastoma cells exposed either to serum-depleted medium or to low-..
  27. Presenilin 2 Ser130Leu mutation in a case of late-onset "sporadic" Alzheimer's disease
    Carmine Tomaino
    J Neurol 254:391-3
  28. When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease
    Michael S Wolfe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, 77 Avenue Louis Pasteur, Harvard Institute of Medicine 754, Boston, Massachusetts 02115, USA
    EMBO Rep 8:136-40
    ..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...
  29. Functional characterization of novel presenilin-2 variants identified in human breast cancers
    M D To
    Fred A Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Oncogene 25:3557-64
    ..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...
  30. Prevalence of pathogenic mutations in an Italian clinical series of patients with familial dementia
    S Signorini
    Neurobiology Lab and Memory Clinic, IRCCS Centro S Giovanni di Dio Fatebenefratelli, via Pilastroni 4, 25123 Brescia, Italy
    Curr Alzheimer Res 1:215-8
    ..identified which, when mutated, cause Familial Alzheimer disease (FAD): the presenilin-1 (PS1), the presenilin-2 (PS2) and the amyloid precursor protein (APP) genes...
  31. Reduction of Ca2+ stores and capacitative Ca2+ entry is associated with the familial Alzheimer's disease presenilin-2 T122R mutation and anticipates the onset of dementia
    Marta Giacomello
    Department of Biomedical Sciences, University of Padova, Via G Colombo, 35121 Padova, Italy
    Neurobiol Dis 18:638-48
    ..Ghidoni, R., Barbiero, L., Binetti, G., Pozzan, T., Fasolato, C., Pizzo, P., 2004. The presenilin 2 M239I mutation associated with Familial Alzheimer's Disease reduces Ca2+ release from intracellular stores...
  32. Identification of the presenilins in hematopoietic cells with localization of presenilin 1 to neutrophil and platelet granules
    Zeljka Korade Mirinics
    Department of Pediatrics, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA
    Blood Cells Mol Dis 28:28-38
    Most cases of familial Alzheimer disease (AD) are caused by mutations in presenilin 1 (PS1) and presenilin 2 (PS2)...
  33. Notch receptor cleavage depends on but is not directly executed by presenilins
    Yoshihito Taniguchi
    Department of Medical Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Faculty of Medicine, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 99:4014-9
    ..We conclude from these experiments that presenilins are critically required for Notch intracellular cleavage but are not themselves directly mediating the cleavage...
  34. Endoproteolysis of presenilin in vitro: inhibition by gamma-secretase inhibitors
    William A Campbell
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Biochemistry 41:3372-9
    ..AD-causing mutations in PS1 and PS2 result in a selective and significant increase in production of the more amyloidogenic Abeta42 peptide...
  35. Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter the sensitivity of PS1 to caspases
    M Van de Craen
    Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Gent, Belgium
    FEBS Lett 445:149-54
    Mutations in the presenilin (PS) genes PSI and PS2 are involved in Alzheimer's disease (AD). Recently, apoptosis-associated cleavage of PS proteins was identified...
  36. The presenilin 2 loop domain interacts with the mu-calpain C-terminal region
    K Shinozaki
    Laboratory of Neurochemistry, National Institute for Physiological Sciences, Myodaiji, Okazaki, Aichi 444, Japan
    Int J Mol Med 1:797-9
    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...
  37. Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment
    J D Buxbaum
    Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nat Med 4:1177-81
    ..Alzheimer disease (AD) cases are caused by mutations in the highly related genes presenilin 1 (PS1) and presenilin 2 (PS2)...
  38. Proteolytic fragments of the Alzheimer's disease associated presenilins-1 and -2 are phosphorylated in vivo by distinct cellular mechanisms
    J Walter
    Department of Molecular Biology, Central Institute of Mental Health, Mannheim, Germany
    Biochemistry 37:5961-7
    ..Interestingly, the potential phosphorylation sites are located directly adjacent to the recently identified caspase cleavage sites...
  39. Amyloid angiopathy in a Volga German family with Alzheimer's disease and a presenilin-2 mutation (N141I)
    D Nochlin
    Department of Pathology Neuropathology, and Alzheimer s Disease Research Center, University of Washington School of Medicine, Seattle 98195 6480, USA
    Ann Neurol 43:131-5
    ..This family emphasizes the need for more investigation into the role of presenilin mutations in amyloid deposition, especially in the cerebral vasculature, and the role of these changes in clinical dementia...
  40. Alzheimer presenilins in the nuclear membrane, interphase kinetochores, and centrosomes suggest a role in chromosome segregation
    J Li
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 90:917-27
    ..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...
  41. Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease
    T W Kim
    Genetics and Aging Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Science 277:373-6
    ..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...
  42. Analysis of the 5' sequence, genomic structure, and alternative splicing of the presenilin-1 gene (PSEN1) associated with early onset Alzheimer disease
    E I Rogaev
    Department of Medicine, University of Toronto, Toronto, Ontario, M5S 3H2, Canada
    Genomics 40:415-24
    Mutations in the human presenilin genes (PSEN1 and PSEN2) are associated with early onset familial Alzheimer disease...
  43. 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
    T Tomita
    Laboratory of Neurochemistry, National Institute for Physiological Sciences, Okazaki, Japan
    Proc Natl Acad Sci U S A 94:2025-30
    ..in 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 ..
  44. The Alzheimer's disease-associated presenilins are differentially phosphorylated proteins located predominantly within the endoplasmic reticulum
    J Walter
    Central Institute of Mental Health, Department of Molecular Biology, Mannheim, Germany
    Mol Med 2:673-91
    ..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...
  45. Participation of presenilin 2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation
    B Wolozin
    Unit on Alzheimer Biology, Laboratory of Clinical Science, National Institute of Mental Health, Building 10, Room 3D41, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Science 274:1710-3
    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...
  46. Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1
    K Duff
    Suncoast Alzheimer s Disease Laboratories, University of South Florida, Tampa, 33612, USA
    Nature 383:710-3
    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...
  47. Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells
    D M Kovacs
    Genetics and Aging Unit, Massachusetts General Hospital East, Harvard Medical School, Charlestown 02129, USA
    Nat Med 2:224-9
    ..These two novel genes, presenilin 1 (PS1) and presenilin 2 (PS2) are members of an evolutionarily conserved gene family...
  48. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene
    E I Rogaev
    Department of Medicine Neurology, University of Toronto, Ontario, Canada
    Nature 376:775-8
    ..Our results also indicate that still other AD susceptibility genes exist...
  49. Candidate gene for the chromosome 1 familial Alzheimer's disease locus
    E Levy Lahad
    Geriatric Research Education, and Clinical Center 182B, Veterans Affairs Medical Center, Seattle, WA 98108, USA
    Science 269:973-7
    A candidate gene for the chromosome 1 Alzheimer's disease (AD) locus was identified (STM2). The predicted amino acid sequence for STM2 is homologous to that of the recently cloned chromosome 14 AD gene (S182)...
  50. Biology of presenilins as causative molecules for Alzheimer disease
    M Nishimura
    Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Ontario, Canada
    Clin Genet 55:219-25
    ..Furthermore, presenilins interact with beta-catenin to form presenilin complexes and presenilin mutations effect beta-catenin signalling pathways...
  51. Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4
    Yuichi Morohashi
    Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113 0033, Japan
    J Biol Chem 277:14965-75
    ..During our attempts to identify binding partners of PS2, we cloned CALP (calsenilin-like protein)/KChIP4, a novel member of calsenilin/KChIP protein family that interacts ..
  52. Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein
    Xiaorei Sai
    Department of Dementia Research, National Institute for Longevity Sciences, 36 3 Gengo, Morioka, Obu, Aichi 474 8522, Japan
    J Biol Chem 277:12915-20
    ..We found that Herp interacts with both PS1 and PS2. Thus, Herp regulates PS-mediated Abeta generation, possibly through its binding to PS...
  53. Identification of a novel family of putative methyltransferases that interact with human and Drosophila presenilins
    S X Zhang
    Program in Developmental Biology, The Hospital for Sick Children, 555 University Avenue, Ontario, Toronto, Canada
    Gene 280:135-44
    ..Taken together, these results suggest that presenilin and Metl functionally and genetically interact during development...
  54. Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins
    W G Annaert
    Laboratory for Neuronal Cell Biology, Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology, KUL Gasthuisberg, B 3000 Leuven, Belgium
    Neuron 32:579-89
    The carboxyl terminus of presenilin 1 and 2 (PS1 and PS2) binds to the neuron-specific cell adhesion molecule telencephalin (TLN) in the brain...
  55. Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2
    E K Choi
    Genetics and Aging Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Biol Chem 276:19197-204
    ..of neuronal calcium-binding proteins that we have previously shown to interact with presenilin 1 (PS1) and presenilin 2 (PS2) holoproteins...
  56. Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation
    A L Mah
    Medical Biotechnology Center, Department of Neurology, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201, USA
    J Cell Biol 151:847-62
    Mutations in the highly homologous presenilin genes encoding presenilin-1 and presenilin-2 (PS1 and PS2) are linked to early-onset Alzheimer's disease (AD)...
  57. Presenilin 2 interacts with sorcin, a modulator of the ryanodine receptor
    E Pack Chung
    Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Biol Chem 275:14440-5
    ..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 ..
  58. Molecular interactions between presenilin and calpain: inhibition of m-calpain protease activity by presenilin-1, 2 and cleavage of presenilin-1 by m-, mu-calpain
    K Maruyama
    Department of Molecular Biology, Tokyo Institute of Psychiatry, Kamikitazawa, Setagaya, Tokyo 156 8585, Japan
    Int J Mol Med 5:269-73
    ..Using the yeast two-hybrid system, the interaction between PS2 loop domain and the C-terminal region of mu-calpain was previously identified...
  59. The transmembrane aspartates in presenilin 1 and 2 are obligatory for gamma-secretase activity and amyloid beta-protein generation
    W T Kimberly
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 275:3173-8
    ..b>Presenilin 2 (PS2) shares substantial sequence and possibly functional homology with PS1...
  60. Interaction of Alzheimer's presenilin-1 and presenilin-2 with Bcl-X(L). A potential role in modulating the threshold of cell death
    B J Passer
    T Cell Apoptosis Unit, Laboratory of Cellular and Molecular Immunology, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 274:24007-13
    ..an anti-apoptotic member of the Bcl-2 family was shown to interact with the carboxyl-terminal fragments of PS1 and PS2 by the yeast two-hybrid system...
  61. Isolation and characterization of novel presenilin binding protein
    A Kashiwa
    Salk Institute for Biological Studies Department of Pathology, University of California, La Jolla, California, USA
    J Neurochem 75:109-16
    ..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...
  62. Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia
    D Arango
    Neuro Sciences Group, Instituto Nacional de Salud, Bogotá, Colombia
    Am J Med Genet 103:138-43
    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)...
  63. Differentially expressed genes in transgenic mice carrying human mutant presenilin-2 (N141I): correlation of selenoprotein M with Alzheimer's disease
    Dae Y Hwang
    Division of Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA, 5 Nokbun dong Eunpyng ku, 122 704, Seoul, Korea
    Neurochem Res 30:1009-19
    ..Thus, the results indicate that SelM might play a suppressive or protective role in the pathology of patients with AD and it will be necessary to investigate further on functional roles of other up- and down-regulated gene in future...
  64. In vitro characterization of the presenilin-dependent gamma-secretase complex using a novel affinity ligand
    Dirk Beher
    Department of Biochemistry and Molecular Biology, Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, United Kingdom
    Biochemistry 42:8133-42
    ..This was also reflected by a co-distribution of both enzyme activities in subcellular fractions enriched for trans-Golgi network membranes...
  65. Expression profiles of two human APH-1 genes and their roles in formation of presenilin complexes
    Shinya Saito
    Department of Demyelinating Disease and Aging, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187 8502, Japan
    Biochem Biophys Res Commun 327:18-22
    ..of APH-1a, but not APH-1b, resulted in impaired maturation of nicastrin and reduced expression of presenilin 1, presenilin 2, and PEN-2 proteins...