PS1

Summary

Gene Symbol: PS1
Description: presenilin 1
Alias: AD3, FAD, PS-1, PS1, S182, presenilin-1
Species: human

Top Publications

  1. pmc Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum
    D Campion
    INSERM EPI 9906, Faculte de Medecine, 76183 Rouen, France
    Am J Hum Genet 65:664-70. 1999
  2. ncbi Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations
    E A Rogaeva
    Centre for Research in Neurodegenerative Diseases and Division of Neurology, Department of Medicine, The University Health Network, Toronto, Ontario, Canada
    Neurology 57:621-5. 2001
  3. ncbi Presenilin-1 mutation L271V results in altered exon 8 splicing and Alzheimer's disease with non-cored plaques and no neuritic dystrophy
    John B J Kwok
    Garvan Institute of Medical Research, Darlinghurst, Sydney 2010, Australia
    J Biol Chem 278:6748-54. 2003
  4. ncbi A novel presenilin 1 L166H mutation in a pseudo-sporadic case of early-onset Alzheimer's disease
    R Pantieri
    Department of Neurosciences, Bellaria Hospital, Via Altura 3, I 40139 Bologna, Italy
    Neurol Sci 26:349-50. 2005
  5. ncbi A novel presenilin 1 deletion (p.L166del) associated with early onset familial Alzheimer's disease
    W D Knight
    Dementia Research Centre, Institute of Neurology, University College London, London, UK
    Eur J Neurol 14:829-31. 2007
  6. ncbi TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity
    Fusheng Chen
    Department of Medicine, and Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada M5S 3H2
    Nature 440:1208-12. 2006
  7. pmc Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations
    Ju Hyun Lee
    Center for Dementia Research, Nathan S Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
    Cell 141:1146-58. 2010
  8. ncbi Novel presenilin 1 mutations associated with early onset of dementia in a family with both early-onset and late-onset Alzheimer disease
    G Devi
    Taub Institute for Research on Alzheimer s Disease and the Aging Brain, The Gertrude Sergievsky Center, Columbia University, New York, NY 10032, USA
    Arch Neurol 57:1454-7. 2000
  9. doi Novel PSEN1 and PGRN mutations in early-onset familial frontotemporal dementia
    Livia Bernardi
    Regional Neurogenetic Centre, ASP Catanzaro, Lamezia Terme CZ, Italy
    Neurobiol Aging 30:1825-33. 2009
  10. ncbi Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer's disease pedigrees and preliminary evidence for association of presenilin-1 mutations with a novel phenotype
    J B Kwok
    Garvan Institute of Medical Research, Sydney, NSW, Australia
    Neuroreport 8:1537-42. 1997

Research Grants

  1. Donna M Wilcock; Fiscal Year: 2016
  2. Suman Jayadev; Fiscal Year: 2015
  3. An iPS Disease-in-a-Dish Model of Familial Alzheimers
    Terrence Town; Fiscal Year: 2012
  4. Mitoenergetic Failure in Brain Aging
    Gregory J Brewer; Fiscal Year: 2013
  5. Mutational Cloning in Familial Dementia and Alzheimers Disease
    Wendy H Raskind; Fiscal Year: 2010
  6. Suman Jayadev; Fiscal Year: 2016
  7. Role of Presenilin in Idiopathic Dilated Cardiomyopathy
    Federica Del Monte; Fiscal Year: 2013
  8. James R Bamburg; Fiscal Year: 2014
  9. Pharmacogenomics of Human P450 Oxidoreductase
    Walter L Miller; Fiscal Year: 2012
  10. Xinmin Simon Xie; Fiscal Year: 2014

Detail Information

Publications267 found, 100 shown here

  1. pmc Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum
    D Campion
    INSERM EPI 9906, Faculte de Medecine, 76183 Rouen, France
    Am J Hum Genet 65:664-70. 1999
    ..3, respectively. We then performed a mutational analysis of the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) in 34 families with ADEOAD ascertained in France...
  2. ncbi Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations
    E A Rogaeva
    Centre for Research in Neurodegenerative Diseases and Division of Neurology, Department of Medicine, The University Health Network, Toronto, Ontario, Canada
    Neurology 57:621-5. 2001
    Mutations in the presenilin-1 gene (PS1) account for a majority of patients with early-onset familial AD. However, the clinical indications and algorithms for genetic testing in dementia are still evolving.
  3. ncbi Presenilin-1 mutation L271V results in altered exon 8 splicing and Alzheimer's disease with non-cored plaques and no neuritic dystrophy
    John B J Kwok
    Garvan Institute of Medical Research, Darlinghurst, Sydney 2010, Australia
    J Biol Chem 278:6748-54. 2003
    ..We postulate that variant plaques observed in this family are due in part to the effects of PS-1deltaexon8 and that interaction between PS-1 and various protein complexes are necessary for neuritic plaque formation...
  4. ncbi A novel presenilin 1 L166H mutation in a pseudo-sporadic case of early-onset Alzheimer's disease
    R Pantieri
    Department of Neurosciences, Bellaria Hospital, Via Altura 3, I 40139 Bologna, Italy
    Neurol Sci 26:349-50. 2005
    ....
  5. ncbi A novel presenilin 1 deletion (p.L166del) associated with early onset familial Alzheimer's disease
    W D Knight
    Dementia Research Centre, Institute of Neurology, University College London, London, UK
    Eur J Neurol 14:829-31. 2007
    ..Analysis of the presenilin 1 gene (PSEN1) revealed a 496_498delCTT mutation at codon 166...
  6. ncbi TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity
    Fusheng Chen
    Department of Medicine, and Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada M5S 3H2
    Nature 440:1208-12. 2006
    The presenilin proteins (PS1 and PS2) and their interacting partners nicastrin, aph-1 (refs 4, 5) and pen-2 (ref...
  7. pmc Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations
    Ju Hyun Lee
    Center for Dementia Research, Nathan S Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
    Cell 141:1146-58. 2010
    ..Here, we show that macroautophagy requires the Alzheimer's disease (AD)-related protein presenilin-1 (PS1)...
  8. ncbi Novel presenilin 1 mutations associated with early onset of dementia in a family with both early-onset and late-onset Alzheimer disease
    G Devi
    Taub Institute for Research on Alzheimer s Disease and the Aging Brain, The Gertrude Sergievsky Center, Columbia University, New York, NY 10032, USA
    Arch Neurol 57:1454-7. 2000
    ..developed dementia in their late 20s and were subsequently found to have novel mutations in codon 434 of the presenilin 1 (PS1) gene on chromosome 14, a G-to-T substitution at nucleotide 1548 and a C-to-G substitution at nucleotide ..
  9. doi Novel PSEN1 and PGRN mutations in early-onset familial frontotemporal dementia
    Livia Bernardi
    Regional Neurogenetic Centre, ASP Catanzaro, Lamezia Terme CZ, Italy
    Neurobiol Aging 30:1825-33. 2009
    ..Mutations in two genes, Microtubule Associated Protein Tau (MAPT) and Progranulin (PGRN), and rarely Presenilin mutations, have been causally linked to this disorder...
  10. ncbi Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer's disease pedigrees and preliminary evidence for association of presenilin-1 mutations with a novel phenotype
    J B Kwok
    Garvan Institute of Medical Research, Sydney, NSW, Australia
    Neuroreport 8:1537-42. 1997
    ..data raise the possibility that the phenotypic spectrum associated with PS-1 mutations may extend beyond typical FAD to include FSP, a disease heretofore unsuspected to bear any relationship to FAD...
  11. ncbi Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response
    T Katayama
    Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    Nat Cell Biol 1:479-85. 1999
    ..the human presenilin-1 (PS1) gene, which is found on chromosome 14, cause early-onset familial Alzheimer's disease (FAD)...
  12. ncbi A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations
    Philippe Marambaud
    Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Cell 114:635-45. 2003
    Presenilin1 (PS1), a protein implicated in Alzheimer's disease (AD), forms complexes with N-cadherin, a transmembrane protein with important neuronal and synaptic functions...
  13. ncbi Gamma-secretase activity of presenilin 1 regulates acetylcholine muscarinic receptor-mediated signal transduction
    Bogdan O Popescu
    Section of Experimental Geriatrics, Karolinska Institutet, Neurotec Department, Kliniskt forskningscentrum, Novum, 141 86 Huddinge, Sweden
    J Biol Chem 279:6455-64. 2004
    Familial Alzheimer's disease (FAD) presenilin 1 (PS1) mutations give enhanced calcium responses upon different stimuli, attenuated capacitative calcium entry, an increased sensitivity of cells to undergo apoptosis, and increased gamma-..
  14. pmc Mutant presenilin 1 expression in excitatory neurons impairs enrichment-mediated phenotypes of adult hippocampal progenitor cells
    Karthikeyan Veeraraghavalu
    Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 110:9148-53. 2013
    Inheritance of mutant presenilin 1 genes (PSEN1) encoding presenilin 1 (PS1)variants causes autosomal dominant forms of familial Alzheimer's disease (FAD)...
  15. ncbi Association between presenilin-1 Glu318Gly mutation and familial Alzheimer's disease in the Australian population
    K Taddei
    Sir James McCusker Alzheimer s Disease Research Unit and University of Western Australia, Department of Surgery, Hollywood Private Hospital, Nedlands, Perth 6009, Australia
    Mol Psychiatry 7:776-81. 2002
    ..the presenilin-1 (PS-1) gene on chromosome 14 account for the majority of early-onset familial Alzheimer's disease (FAD) cases...
  16. ncbi A mutation screening by DHPLC of PSEN1 and APP genes reveals no significant variation associated with the sporadic late-onset form of Alzheimer's disease
    Renato Scacchi
    CNR Institute of Molecular Biology and Pathology, c o Department of Genetics and Molecular Biology, University La Sapienza, P le Aldo Moro 5, 00185 Rome, Italy
    Neurosci Lett 418:282-5. 2007
    ..We concluded that the variation in the screened exons of the APP and PSEN1 genes, reportedly associated with familial AD, is not present in LOAD...
  17. doi A novel PSEN1 mutation (K239N) associated with Alzheimer's disease with wide range age of onset and slow progression
    A Lladó
    Alzheimer s Disease and Other Cognitive Disorders Unit, Institut d Investigacio Biomedica August Pi i Sunyer IDIBAPS, Hospital Clinic, Barcelona, Spain
    Eur J Neurol 17:994-6. 2010
    ..To describe a novel mutation (K239N) in the PSEN1 associated with familial Alzheimer's disease (AD)...
  18. ncbi Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3
    M Cruts
    Laboratory of Neurogentics, Flemish Insitute for Biotechnology, Born Bunge Foundation, University of Antwerp, Belgium
    Hum Mol Genet 4:2363-71. 1995
    ..Positional cloning efforts have identified a novel gene S182 or presenilin 1 as the AD3 gene...
  19. pmc The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and gamma-secretase
    Emmanuelle Six
    Unité de Biologie Moléculaire de l Expression Génique, Unité de Recherche Associée 2582, Centre National de la Recherche Scientifique, Institut Pasteur, 75724 Paris Cedex 15, France
    Proc Natl Acad Sci U S A 100:7638-43. 2003
    ..Therefore Dll1 is a substrate for regulated intramembrane proteolysis, and its intracellular region possibly fulfills a specific function in the nucleus...
  20. ncbi Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease
    M Cruts
    Laboratory of Neurogenetics, Flanders Interuniversity Institute for Biotechnology VIB, Born Bunge Foundation BBS, University of Antwerp UIA, Department of Biochemistry, Antwerpen, Belgium
    Hum Mol Genet 7:43-51. 1998
    ..Further, polymorphisms were detected in the promoter and the 5'-non-coding region of PS -1 and in intronic and exonic sequences of PS -2 that will be useful in genetic association studies...
  21. ncbi Decreased Abeta secretion by cells expressing familial Alzheimer's disease-linked mutant presenilin 1
    Masafumi Shimojo
    Laboratory for Alzheimer s Disease, RIKEN Brain Science Institute, Wako Shi, Saitama, Japan
    Neurosci Res 57:446-53. 2007
    ..Familial Alzheimer's disease (FAD) results from PS mutations, which may alter gamma-secretase activity to enhance the production of highly aggregable ..
  22. pmc Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations
    Huiping Tu
    Department of Physiology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Cell 126:981-93. 2006
    ..Mutations in presenilins 1 and 2 (PS1 and PS2) account for approximately 40% of familial AD (FAD) cases...
  23. ncbi Expression of presenilin 1 and 2 (PS1 and PS2) in human and murine tissues
    M K Lee
    Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 16:7513-25. 1996
    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)...
  24. ncbi Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity
    M S Wolfe
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nature 398:513-7. 1999
    ..residues are critical for both presenilin-1 endoproteolysis and gamma-secretase activity, and suggest that presenilin 1 is either a unique diaspartyl cofactor for gamma-secretase or is itself gamma-secretase, an autoactivated ..
  25. ncbi A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families
    E S Athan
    The Gertrude H Sergievsky Center, Columbia University College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA
    JAMA 286:2257-63. 2001
    ..Genetic determinants of Alzheimer disease (AD) have not been comprehensively examined in Caribbean Hispanics, a population in the United States in whom the frequency of AD is higher compared with non-Hispanic whites...
  26. ncbi The role of presenilin cofactors in the gamma-secretase complex
    Nobumasa Takasugi
    Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1 Hongo, Bunkyoku, Tokyo 113 0033, Japan
    Nature 422:438-41. 2003
    Mutations in presenilin genes account for the majority of the cases of the familial form of Alzheimer's disease (FAD)...
  27. ncbi Biological effects of four PSEN1 gene mutations causing Alzheimer disease with spastic paraparesis and cotton wool plaques
    Cecile Dumanchin
    INSERM U614, IFRMP, Faculte de Medecine, Rouen, France
    Hum Mutat 27:1063. 2006
    ..We conclude that none of the previously proposed mechanisms, i.e. exceptionally large increases in secreted Abeta42 levels or loss of PSEN1 exons 8 or 9, provides complete explanation of the CWP/SP phenotype...
  28. pmc The role of variation at AβPP, PSEN1, PSEN2, and MAPT in late onset Alzheimer's disease
    Amy Gerrish
    MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
    J Alzheimers Dis 28:377-87. 2012
    ..However, the gene-wide effect observed at MAPT indicates a possible contribution to disease risk which requires further study...
  29. ncbi 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. 1996
    ..These two novel genes, presenilin 1 (PS1) and presenilin 2 (PS2) are members of an evolutionarily conserved gene family...
  30. ncbi 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. 1998
    Most early-onset familial Alzheimer disease (AD) cases are caused by mutations in the highly related genes presenilin 1 (PS1) and presenilin 2 (PS2)...
  31. ncbi 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. 2003
    ..This was also reflected by a co-distribution of both enzyme activities in subcellular fractions enriched for trans-Golgi network membranes...
  32. ncbi Gamma-secretase exists on the plasma membrane as an intact complex that accepts substrates and effects intramembrane cleavage
    Jay H Chyung
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 280:4383-92. 2005
    ....
  33. pmc Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease
    Bart De Strooper
    KULeuven and Flanders Interuniversitary Institute for Biotechnology VIB, Centre for Human Genetics, Herestraat 49, 3000 Leuven, Belgium
    EMBO Rep 8:141-6. 2007
    ..In this review, I evaluate the implications of this model for the amyloid-cascade hypothesis and for the efficacy of presenilin/gamma-secretase as a drug target...
  34. ncbi Extreme cerebrospinal fluid amyloid beta levels identify family with late-onset Alzheimer's disease presenilin 1 mutation
    John S K Kauwe
    Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
    Ann Neurol 61:446-53. 2007
    ..Mutations in presenilin 1 (PSEN1) are known to cause AD and change Abeta levels...
  35. pmc Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1
    Omar Nelson
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    J Clin Invest 117:1230-9. 2007
    Mutations in presenilins are responsible for approximately 40% of all early-onset familial Alzheimer disease (FAD) cases in which a genetic cause has been identified...
  36. pmc Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria
    Estela Area-Gomez
    Department of Neurology, Columbia University Medical Center, New York, New York, USA
    Am J Pathol 175:1810-6. 2009
    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 ..
  37. pmc A presenilin-1 mutation identified in familial Alzheimer disease with cotton wool plaques causes a nearly complete loss of gamma-secretase activity
    Elizabeth A Heilig
    Center for Human Genetic Research and Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Biol Chem 285:22350-9. 2010
    Mutations in presenilin-1 and presenilin-2 (PS1 and PS2) are the most common cause of familial Alzheimer disease...
  38. pmc Presenilin 1 mutants impair the self-renewal and differentiation of adult murine subventricular zone-neuronal progenitors via cell-autonomous mechanisms involving notch signaling
    Karthikeyan Veeraraghavalu
    Department of Neurobiology, The University of Chicago, Chicago, Illinois 60637, USA
    J Neurosci 30:6903-15. 2010
    ..While genetic ablation studies have revealed a role for presenilin 1 (PS1) in embryonic neurogenesis, little information has emerged regarding the potential effects of FAD-linked ..
  39. pmc Presenilin/γ-secretase regulates neurexin processing at synapses
    Carlos A Saura
    Institut de Neurociencies, Departament de Bioquimica i Biologia Molecular, Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas CIBERNED, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain
    PLoS ONE 6:e19430. 2011
    ..Interestingly, presenilin 1 (PS1) is recruited to glutamatergic terminals mediated by neuroligin-1, thus concentrating PS1 at terminals ..
  40. pmc Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families
    Carlos Cruchaga
    Department of Psychiatry and Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University, St Louis, Missouri, United States of America
    PLoS ONE 7:e31039. 2012
    ..This study clearly demonstrates that rare variants in these genes could explain an important proportion of genetic heritability of AD, which is not detected by GWAS...
  41. doi PSEN1 mutation carriers present lower cerebrospinal fluid amyoid-β42 levels than sporadic early-onset Alzheimer's disease patients but no differences in neuronal injury biomarkers
    Mircea Balasa
    Alzheimer s Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clinic, Institut d Investigacio Biomedica August Pi i Sunyer IDIBAPS, Barcelona, Spain
    J Alzheimers Dis 30:605-16. 2012
    ..The lack of significant differences in relation to t-tau and p-tau levels and to the severity of CTh or grey matter loss suggests a similar level of neuronal injury despite higher Aβ(42) load in PSEN1...
  42. ncbi Phosphorylation, subcellular localization, and membrane orientation of the Alzheimer's disease-associated presenilins
    B De Strooper
    Experimental Genetics Group, Belgium
    J Biol Chem 272:3590-8. 1997
    ..In COS-1 cells low amounts of intact endogeneous presenilin 1 migrating at 45 kDa are detected together with relative larger amounts of presenilin 1 fragments migrating ..
  43. ncbi The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains beta-catenin
    G Yu
    Centre for Research in Neurodegenerative Diseases, Departments of Medicine and Medical Biophysics, University of Toronto, Toronto, Ontario M5S 3H2, Canada
    J Biol Chem 273:16470-5. 1998
    ..velocity and discontinuous sucrose gradient analysis to investigate the distribution and native conformation of PS1 and PS2 during this regulated processing in cultured cells and in brain...
  44. ncbi Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis
    H Steiner
    Department of Molecular Biology, Central Institute of Mental Health, J5, 68159 Mannheim, Germany
    Biochemistry 38:14600-5. 1999
    ..The presenilin (PS) proteins play a key role in Abeta generation. FAD-associated mutations in PS1 and PS2 enhance the production of Abeta42, and PS1 is required for physiological Abeta ..
  45. ncbi Evidence that the "NF" motif in transmembrane domain 4 of presenilin 1 is critical for binding with PEN-2
    Seong Hun Kim
    Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 280:41953-66. 2005
    Macromolecular complexes containing presenilins (PS1 and PS2), nicastrin, anterior pharynx defective phenotype 1 (APH-1), and PS enhancer 2 (PEN-2) mediate the intramembranous, gamma-secretase cleavage of beta-amyloid precursor protein (..
  46. ncbi Presenilin-1 interacts with plakoglobin and enhances plakoglobin-Tcf-4 association. Implications for the regulation of beta-catenin/Tcf-4-dependent transcription
    Imma Raurell
    Unitat de Biofisica, Departament de Bioquimica i Biologia Molecular, Facultat de Medicina, Universitat Autonoma de Barcelona, E 08193 Bellaterra, Spain
    J Biol Chem 281:1401-11. 2006
    Alzheimer disease-linked Presenilin-1 (PS1) is a negative modulator of beta-catenin/Tcf-4 activity. However, the mechanism underlying this effect is not well understood...
  47. ncbi Presenilin-1 maintains a nine-transmembrane topology throughout the secretory pathway
    Dragana Spasic
    Laboratory of Membrane Trafficking, Department of Human Genetics, Gasthuisberg, Katholieke Universiteit Leuven VIB11, B 3000 Leuven, Belgium
    J Biol Chem 281:26569-77. 2006
    ..We revisited presenilin-1 topology by inserting glycosylation consensus sequences in human PS1 and expressing the obtained mutants in a presenilin-1 and 2 knock-out background...
  48. ncbi Presenilin-1 mutation activates the signaling pathway of caspase-4 in endoplasmic reticulum stress-induced apoptosis
    Futoshi Yukioka
    Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    Neurochem Int 52:683-7. 2008
    In the previous reports, we showed that the familial Alzheimer's disease (AD)-linked presenilin-1 (PS1) mutation induced the fragility to the endoplasmic reticulum (ER) stress and that caspase-4 mediates ER stress-induced- and beta-..
  49. ncbi Presenilin 1 interaction in the brain with a novel member of the Armadillo family
    J Zhou
    Department of Neurology, Brigham and Women s Hospital, Boston, MA, USA
    Neuroreport 8:2085-90. 1997
    One approach to understanding the function of presenilin 1 (PS1), is to discover those proteins with which it interacts. Evidence for a function in developmental patterning came from C...
  50. ncbi Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo
    G Thinakaran
    Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Neuron 17:181-90. 1996
    ..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 ..
  51. ncbi Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch
    W J Ray
    Departments of Psychiatry and Genetics, Washington University Medical School, St Louis, Missouri 63110, USA
    J Biol Chem 274:36801-7. 1999
    Presenilin-1 (PS1), a polytopic membrane protein primarily localized to the endoplasmic reticulum, is required for efficient proteolysis of both Notch and beta-amyloid precursor protein (APP) within their trans- membrane domains...
  52. pmc Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state
    Y M Li
    Department of Biological Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Proc Natl Acad Sci U S A 97:6138-43. 2000
    ..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)...
  53. ncbi Presenilin 1 regulates beta-catenin-mediated transcription in a glycogen synthase kinase-3-independent fashion
    J J Palacino
    Department of Pharmacology and Neuroscience Program, Loyola University Medical Center, Maywood, Illinois 60153, USA
    J Biol Chem 276:38563-9. 2001
    b>Presenilin 1 (PS1) is linked with Alzheimer's disease but exhibits functional roles regulating growth and development. For instance, PS1 binds to beta-catenin and modulates beta-catenin signaling...
  54. ncbi 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. 2001
    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. ncbi Presenilin 1 is required for maturation and cell surface accumulation of nicastrin
    Jae Yoon Leem
    Department of Neurobiology, Committee on Neurobiology, The University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 277:19236-40. 2002
    ..Presenilins (PS1 and PS2) facilitate the final step in Abeta production, the intramembranous gamma-secretase cleavage of amyloid ..
  56. pmc Presenilin-1 affects trafficking and processing of betaAPP and is targeted in a complex with nicastrin to the plasma membrane
    Christoph Kaether
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Cell Biol 158:551-61. 2002
    ..The intramembraneous gamma-secretase cleavage critically depends on the activity of presenilins (PS1 and PS2)...
  57. ncbi Syndecan 3 intramembrane proteolysis is presenilin/gamma-secretase-dependent and modulates cytosolic signaling
    Joachim G Schulz
    Glycobiology and Developmental Genetics, University of Leuven, Leuven, Belgium
    J Biol Chem 278:48651-7. 2003
    ..The cleavage is mediated by presenilin/gamma-secretase complex and negatively regulates the plasma membrane targeting of the transcriptional cofactor CASK...
  58. pmc PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations
    Lia Baki
    Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY 10029, USA
    EMBO J 23:2586-96. 2004
    ..Here we show that PS1, a protein involved in familial Alzheimer's disease (FAD), promotes cell survival by activating the PI3K/Akt cell survival signaling...
  59. ncbi Presenilins mediate phosphatidylinositol 3-kinase/AKT and ERK activation via select signaling receptors. Selectivity of PS2 in platelet-derived growth factor signaling
    David E Kang
    Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 280:31537-47. 2005
    The Alzheimer's disease-linked genes, PS1 and PS2, are required for intramembrane proteolysis of multiple type I proteins, including Notch and amyloid precursor protein...
  60. ncbi 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. 1995
    ..gene (E5-1) encoded on chromosome 1 which has substantial nucleotide and amino-acid sequence similarity to the S182 gene on chromosome 14q24.3...
  61. ncbi A mutation in Alzheimer's disease destroying a splice acceptor site in the presenilin-1 gene
    J Perez-Tur
    Department of Psychiatry, University of South Florida, Tampa 33613, USA
    Neuroreport 7:297-301. 1995
    ..The importance of this observation is discussed...
  62. ncbi Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue
    M B Podlisny
    Center for Neurologic Diseases, Harvard Medical School, Boston, Massachusetts, 02115, USA
    Neurobiol Dis 3:325-37. 1997
    ..at an early age and develop a clinically and pathologically severe form of familial Alzheimer's disease (FAD)...
  63. pmc Interaction of presenilins with the filamin family of actin-binding proteins
    W Zhang
    Department of Pediatrics and Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 18:914-22. 1998
    Mutations in presenilin genes PS1 and PS2 account for approximately 50% of early-onset familial Alzheimer's disease (FAD)...
  64. ncbi Isolation of human delta-catenin and its binding specificity with presenilin 1
    H Tanahashi
    Division of Demyelinating Disease and Aging, National Institute of Neuroscience, Kodaira, Tokyo, Japan
    Neuroreport 10:563-8. 1999
    ..that delta-catenin interacted with a hydrophilic loop region in the endoproteolytic C-terminal fragment of PS1, but not with that of PS-2. These results suggest that PS1 and PS2 partly differ in function...
  65. pmc A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions
    Philippe Marambaud
    Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA
    EMBO J 21:1948-56. 2002
    ..Here we show that presenilin-1 (PS1), a protein involved in Alzheimer's disease, controls a gamma-secretase-like cleavage of E-cadherin...
  66. ncbi The presenilin proteins are components of multiple membrane-bound complexes that have different biological activities
    YongJun Gu
    Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, 6 Queen s Park Crescent West, Toronto, Ontario M5S 3H2, Canada
    J Biol Chem 279:31329-36. 2004
    ..is a stable and abundant intermediate complex of approximately 440 kDa, which contains aph-1, pen-2, nicastrin, and PS1. However, it is the very low abundance, high mass (>/=670 kDa) heteromeric complexes that are associated with ..
  67. ncbi Purification and characterization of the human gamma-secretase complex
    Patrick C Fraering
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 43:9774-89. 2004
    ....
  68. ncbi Presenilin-1 mutation E318G and familial Alzheimer's disease in the Italian population
    Diego Albani
    Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Via Eritrea 62, 20157 Milan, Italy
    Neurobiol Aging 28:1682-8. 2007
    ..Nevertheless, this mutation was reported to be a genetic risk factor for familial Alzheimer's disease (FAD) in the Australian population...
  69. pmc Mechanism of Ca2+ disruption in Alzheimer's disease by presenilin regulation of InsP3 receptor channel gating
    King Ho Cheung
    Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Neuron 58:871-83. 2008
    ..Here, we demonstrate that FAD mutant PS1 (M146L)and PS2 (N141I) interact with the inositol 1,4,5-trisphosphate receptor (InsP3R) Ca2+ release channel and ..
  70. pmc Pen2 and presenilin-1 modulate the dynamic equilibrium of presenilin-1 and presenilin-2 gamma-secretase complexes
    Lisa Placanica
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    J Biol Chem 284:2967-77. 2009
    ..We show that our in vitro assay system recapitulates the effect of PS1 mutations on the Abeta42:Abeta40 ratio observed in cell and animal models...
  71. ncbi Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
    R Sherrington
    Department of Medicine Neurology, University of Toronto, Ontario, Canada
    Nature 375:754-60. 1995
    ..One of these transcripts (S182) corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an ..
  72. ncbi Mutations of the presenilin I gene in families with early-onset Alzheimer's disease
    D Campion
    Laboratorie de Génétique Moléculaire, CHU de Rouen, France
    Hum Mol Genet 4:2373-7. 1995
    ..Alzheimer' s disease (EOAD)for mutations in the coding region of the presenilin I (PSNLI) gene corresponding to the AD3 locus on chromosome 14q24.3...
  73. ncbi 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. 1996
    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...
  74. ncbi Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation
    F Lopera
    Department of Neurology, Antioquia University School of Medicine, Medellin, Colombia
    JAMA 277:793-9. 1997
    ..To characterize clinical features of a very large pedigree with early-onset Alzheimer disease (AD) in which all affected individuals carry the identical glutamic acid-to-alanine mutation at codon 280 in the presenilin-1 gene...
  75. ncbi 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. 1997
    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...
  76. pmc A presenilin-1 truncating mutation is present in two cases with autopsy-confirmed early-onset Alzheimer disease
    C Tysoe
    Department of Medical Genetics, Addenbrooke s NHS Trust, Cambridge, CB2 2QQ, United Kingdom
    Am J Hum Genet 62:70-6. 1998
    ..Since no other mutations or polymorphisms were detected in our patients, mutations in the coding regions and splice consensus sequences of PS-1 are likely to be rare in EOAD cases unselected for family history...
  77. ncbi Presenilin mutations in Alzheimer's disease
    M Cruts
    Flanders Interuniversity Institute for Biotechnology, BornBunge Foundation, University of Antwerp, Department of Biochemistry, Antwerpen, Belgium
    Hum Mutat 11:183-90. 1998
    ..In vivo and in vitro studies have linked PS mutations to amyloid deposition, an early pathological event in AD brains...
  78. ncbi Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene
    P Poorkaj
    Department of Medicine, University of Washington, Seattle, USA
    Hum Mutat 11:216-21. 1998
    ..Two of these new mutations are found within predicted transmembrane domains (TMDs 4, 7, and 8). The A426P mutation is the most C-terminal PS-1 mutation identified to date...
  79. ncbi Direct association of presenilin-1 with beta-catenin
    M Murayama
    Laboratory for Alzheimer s Disease, Brain Science Institute, RIKEN, Saitama, Japan
    FEBS Lett 433:73-7. 1998
    ..However, the mechanism through which PS1 causes AD is unclear...
  80. ncbi Direct interaction of Alzheimer's disease-related presenilin 1 with armadillo protein p0071
    B Stahl
    Max Planck Institute for Experimental Medicine, 37075 Gottingen, Germany
    J Biol Chem 274:9141-8. 1999
    ..to identify an interacting armadillo protein, termed p0071, that binds specifically to the hydrophilic loop of presenilin 1. In vivo, the presenilins constitutively undergo proteolytic processing, forming two stable fragments...
  81. ncbi A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain
    B De Strooper
    Neuronal Cell Biology and Gene Transfer Laboratory, Flanders Institute for Biotechnology VIB4, Center for Human Genetics, KU Leuven, Belgium
    Nature 398:518-22. 1999
    ..A deficiency in presenilin-1 (PS1) inhibits processing of APP by gamma-secretase in mammalian cells, and genetic interactions between Notch and PS1 ..
  82. pmc A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein
    S M Stabler
    Medical Biotechnology Center and Department of Neurology, University of Maryland, Baltimore, Maryland 21201, USA
    J Cell Biol 145:1277-92. 1999
    It is well established that mutations in the presenilin 1 and 2 genes cause the majority of early onset Alzheimer's disease (AD). However, our understanding of the cellular functions of the proteins they encode remains rudimentary...
  83. pmc High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes
    U Finckh
    Department of Human Genetics, University Hospital Eppendorf, University of Hamburg, Germany
    Am J Hum Genet 66:110-7. 2000
    Clinical differential diagnosis of early-onset dementia (EOD) includes familial Alzheimer disease (FAD) and hereditary prion disease...
  84. ncbi Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts
    A Georgakopoulos
    Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA
    Mol Cell 4:893-902. 1999
    ..That PS1 is a constituent of the cadherin/catenin complex makes that complex a potential target for PS1 FAD mutations.
  85. ncbi Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing
    G Yu
    Centre for Research in Neurodegenerative Diseases, Toronto Western Hospital, and Department of Medicine Neurology, University of Toronto, Ontario, Canada
    Nature 407:48-54. 2000
    Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2...
  86. ncbi Murine notch homologs (N1-4) undergo presenilin-dependent proteolysis
    M T Saxena
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Ave, St Louis, MO 63110, USA
    J Biol Chem 276:40268-73. 2001
    ..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...
  87. ncbi 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, Bogota, Colombia
    Am J Med Genet 103:138-43. 2001
    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)...
  88. pmc Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production
    Tobias Moehlmann
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Proc Natl Acad Sci U S A 99:8025-30. 2002
    ..mutations causing familial AD (FAD) that all cause increased production of Abeta(42) have been found in the PS1 gene...
  89. pmc Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formation
    Dieter Edbauer
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Schillerstrasse 44, Ludwig Maximilians University, 80336 Munich, Germany
    Proc Natl Acad Sci U S A 99:8666-71. 2002
    ..Recent evidence suggests that the presenilin (PS) proteins, PS1 and PS2, may be gamma-secretases...
  90. ncbi The presenilin 1 deltaE9 mutation gives enhanced basal phospholipase C activity and a resultant increase in intracellular calcium concentrations
    Angel Cedazo-Minguez
    Section of Experimental Geriatrics, Karolinska Institutet, Neurotec, Kliniskt Forskningscentrum KFC, 141 86 Huddinge, Sweden
    J Biol Chem 277:36646-55. 2002
    We studied effects of the familial Alzheimer's disease presenilin 1 (PS1) exon 9 deletion (PS1-DeltaE9) mutation on basal and carbachol-stimulated phosphoinositide (PI) hydrolysis and intracellular Ca(2+) concentrations ([Ca(2+)](i)) in ..
  91. ncbi 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. 2002
    ..Recently, PEN-2 has been implicated in gamma-secretase function. Here we identify PEN-2 as a critical component of PS1/gamma-secretase and PS2/gamma-secretase complexes...
  92. ncbi 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. 2002
    ..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...
  93. ncbi Gamma-secretase activity is not involved in presenilin-mediated regulation of beta-catenin
    Jere E Meredith
    Bristol Myers Squibb Company, The Pharmaceutical Research Institute, Experimental Station, Route 141 and Henry Clay Rd, Wilmington, DE 19880, USA
    Biochem Biophys Res Commun 299:744-50. 2002
    ..In addition, presenilin 1 (PS-1) binds to members of the armadillo family of proteins...
  94. ncbi APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin.nicastrin complexes
    YongJun Gu
    Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Ontario M5S 3H2, Canada
    J Biol Chem 278:7374-80. 2003
    ..to nicastrin and PEN-2, APH-1 itself is only modestly destabilized in cells lacking functional expression of presenilin 1 or presenilin 2...
  95. ncbi Reconstitution of gamma-secretase activity
    Dieter Edbauer
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Nat Cell Biol 5:486-8. 2003
    ..Thus, the biological activity of gamma-secretase is reconstituted by the co-expression of human PS, Nct, APH-1 and PEN-2 in yeast...
  96. pmc Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2
    W Taylor Kimberly
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:6382-7. 2003
    ..These findings suggest that the four membrane proteins comprise the limiting components of gamma-secretase and coassemble to form the active enzyme in mammalian cells...
  97. ncbi Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport
    Gustavo Pigino
    Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030, USA
    J Neurosci 23:4499-508. 2003
    ..Recent work indicates that presenilin 1 (PS1) interacts with glycogen synthase kinase 3beta (GSK3beta)...
  98. ncbi 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
    Omar Nyabi
    Neuronal Cell Biology and Gene Transfer Laboratory, Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology VIB4 and K U Leuven, 3000 Leuven, Belgium
    J Biol Chem 278:43430-6. 2003
    ....
  99. ncbi Oligomerization of human presenilin-1 fragments
    Sébastien S Hébert
    Molecular and Human Genetics Unit, CHUQ Pavillon St François d Assise, 10 rue de l Espinay, Quebec, QC, Canada G1L 3L5
    FEBS Lett 550:30-4. 2003
    To gain insight into presenilin-1 (PS1) structural aspects, we explored the structure-function relationship of its N- and C-terminal (NTF and CTF, respectively) complexes...
  100. ncbi A novel highly pathogenic Alzheimer presenilin-1 mutation in codon 117 (Pro117Ser): Comparison of clinical, neuropathological and cell culture phenotypes of Pro117Leu and Pro117Ser mutations
    Wieslaw K Dowjat
    Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA
    J Alzheimers Dis 6:31-43. 2004
    A novel presenilin-1 (PS1) mutation (P117S) in an American pedigree is described...
  101. ncbi Nonsteroidal anti-inflammatory drugs lower Abeta42 and change presenilin 1 conformation
    Alberto Lleo
    Alzheimer Research Unit, Massachusetts General Hospital, 114 16th St, Charlestown, Massachusetts 02129, USA
    Nat Med 10:1065-6. 2004
    ..energy transfer method, that Abeta(42)-lowering NSAIDs specifically affect the proximity between APP and presenilin 1 and alter presenilin 1 conformation both in vitro and in vivo, suggesting a novel allosteric mechanism of action...

Research Grants73

  1. Donna M Wilcock; Fiscal Year: 2016
    ..The overall goal of our proposal is to determine the time-course of CBVD pathology when we generate CBVD in APP/PS1 transgenic mice, determine the roles of inflammation and MMPs in the generation of microhemorrhage and vasogenic ..
  2. Suman Jayadev; Fiscal Year: 2015
    ..Alzheimer disease (fAD) is associated with mutations in the genes encoding amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2)...
  3. An iPS Disease-in-a-Dish Model of Familial Alzheimers
    Terrence Town; Fiscal Year: 2012
    ..In this regard, transgenic mice harboring mutations in one or more genes that cause early-onset familial AD (fAD) have been enormously helpful, both in terms of interrogating potential therapeutic targets and also for ..
  4. Mitoenergetic Failure in Brain Aging
    Gregory J Brewer; Fiscal Year: 2013
    ..higher levels of ROS with lower glutathione antioxidant and maintain a more oxidized redox potential [ NAD(P)H / FAD ], all of which contribute to increased susceptibility to toxic stressors such as glutamate and beta-amyloid...
  5. Mutational Cloning in Familial Dementia and Alzheimers Disease
    Wendy H Raskind; Fiscal Year: 2010
    ..We will employ newly available powerful sequencing and bioinformatics techniques to detect causative mutations in families with apparent autosomal dominant dementia where the available affected persons are too few for linkage analyses. ..
  6. Suman Jayadev; Fiscal Year: 2016
    ..2 (PSEN2) deficiency is associated with an exaggerated pro-inflammatory response in microglia and that the fAD associated PSEN2 N141I mutation leads to decreased gamma- secretase activity in microglia...
  7. Role of Presenilin in Idiopathic Dilated Cardiomyopathy
    Federica Del Monte; Fiscal Year: 2013
    ..The incidence, prognosis and therapeutic option for iDCM therefore may be greatly advanced by establishing a fundamental understanding of key factors leading to the disease. ..
  8. James R Bamburg; Fiscal Year: 2014
    ..rods that initiate and exacerbate synaptic dysfunction typical of both sporadic (SAD) and familial AD (FAD)...
  9. Pharmacogenomics of Human P450 Oxidoreductase
    Walter L Miller; Fiscal Year: 2012
    ..POR is a 680 amino-acid, 78 kDa protein that contains two flavins, a flavin adenine dinucleotide moiety (FAD), and a flavin mononucleotide (FMN). There is substantial genetic variation in the hepatic P450 enzymes...
  10. Xinmin Simon Xie; Fiscal Year: 2014
    ..neurobehavioral and neuropathological outcomes) of lead compounds by oral administration to the AD model APP/PS1 mice...
  11. Izumi Maezawa; Fiscal Year: 2016
    ..1 to AD-like pathology and cognitive deficits seen in the APPswe/PS1dE9 (APP-PS1) model using the genetic knockout approach. We will cross-breed APP-PS1 mice with KCa3...
  12. Development of a HTS assay for modulators of presenilin 1 conformation
    Oksana Berezovska; Fiscal Year: 2010
    ..final enzymatic step in generating Ass via cleavage of the amyloid precursor protein (APP) is performed by the presenilin 1 (PS1) dependent ?-secretase complex...
  13. Central and endocrine stress pathway contributions to Alzheimers Disease
    Nicholas J Justice; Fiscal Year: 2013
    ..First, I plan to characterize aging mice carrying Familial Alzheimer's Disease (FAD) mutations that acquire AD pathologies, for changes in anxiety related behavior, HPA axis function, and molecular ..
  14. Zoran Brkanac; Fiscal Year: 2015
    ..This study will also establish the utility of our innovative analytical approach combined with exome sequencing as a powerful method for the identification of genes for Mendelian forms of common genetically heterogeneous disorders. ..
  15. Guojun Bu; Fiscal Year: 2016
    ..out in the background of apoE3-targeted replacement (TR) mice or apoE4-TR mice, without or with amyloid model APP/PS1 background...
  16. Mitochondrial Fission and Fusion in Alzheimer Disease
    Xiongwei Zhu; Fiscal Year: 2012
    ..mitochondrial fission/fusion in vitro;Aim2) To Explore the Mechanisms of ADDL-induced DLP1 Reduction;Aim3) mutant PS1 causes mitochondrial abnormalities and neuronal dysfunction at least in part through its interaction with DLP1 and ..
  17. Identifying Alzheimer's disease genes using genomic and family data
    ELIZABETH MARCHANI BLUE; Fiscal Year: 2012
    ..In addition, this study will provide important information about the genetic architecture of AD and approaches to identifying the associated risk variants, which will be useful for design of complex-trait studies. ..
  18. ELIZABETH MARCHANI BLUE; Fiscal Year: 2016
    ..In addition, this study will provide important information about the genetic architecture of AD and approaches to identifying the associated risk variants, which will be useful for design of complex-trait studies. ..
  19. Nikolaos K Robakis; Fiscal Year: 2014
    ..toxicity and that the neuroprotective activities of ephrinBLs depend on EphB receptors (EphBRs) and presenilini (PS1), a protein involved in familial AD (FAD)...
  20. Insulin/Insulin receptor modulate APP phosphorylation and dementia
    LUCIANO D'ADAMIO; Fiscal Year: 2013
    ..two subunits of an enzyme that regulates APP processing, PSEN1 and PSEN2, cause Familial Alzheimer's disease (FAD). New evidence from our laboratory further stress this link between APP processing and dementia...
  21. Hui Zheng; Fiscal Year: 2016
    ..Mutations in APP and presenilin (PSEN) genes lead to early onset of familial AD (FAD), establishing their critical roles in AD pathogenesis...
  22. Alzheimers Disease Mechanism & Experimental Therapeutic
    Philip Wong; Fiscal Year: 2009
    ..the capacity of the brain to repair itself;3) To determine whether Abeta burden can be reduced in brains of mutant PS1;APP mice by genetically modulating the levels of BACE1 and/or components of the gamma-secretase complex;4) To test ..
  23. Steven W Barger; Fiscal Year: 2014
    ..Preliminary data indicate that such PS1 mutants reduce the steady-state levels of LRPs below what is seen with wild-type PS1...
  24. Targeted Mouse Models of Alzheimer Disease
    Ken Ichiro Fukuchi; Fiscal Year: 2001
    ..Inherited mutations in the gene coding for presenilin 1 (PS1) cause 18 to 50% of the early onset FAD cases...
  25. Non-invasive Assessment of Tissue Engineered Human Oral Mucosa
    Mary Ann Mycek; Fiscal Year: 2012
    ..of the cellular component of the EVPOME via the redox state of endogenous fluorophores flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH)...
  26. MEHNAAZ FATIMA ALI; Fiscal Year: 2015
    ..The redox properties of GOx are dependent on the presence of its co-factor flavin adenine dinucleotide (FAD). The removal of FAD reversibly renders the enzyme inactive without permanently denaturing the enzyme structure...
  27. Todd C Holmes; Fiscal Year: 2016
    ..sensitivity is mediated through light-activated changes in the redox state of the flavin adenine dinucleotide (FAD) chromophore bound to dCry which then couples to a redox sensor in cytoplasmic potassium channel subunits and ..
  28. RUDOLPH EMILE TANZI; Fiscal Year: 2016
    ..neurons and learn if certain synaptotagmins we recently identified by proteomics as novel interactors of both PS1 and APP enable PS to change its conformation rapidly and reversibly in response to Ca2+ influx at the synapse, ..
  29. Characterization of an FAD pathogenic PS1 mutation with complete loss of activity
    HANNAH LOUISE BRAUTIGAM; Fiscal Year: 2013
    ..Most FAD cases result in mutations in a polytopic membrane protein, presenilin 1 (PS1), that contains the active site for the 3-secretase enzyme, and which, in turn, determines the carboxyl ..
  30. Airong Li; Fiscal Year: 2014
    ..Genetics plays a significant role in the etiology of HS. Presenilins (PSEN1 and PSEN2) encodes homologous PS1 and PS2 proteins, which are components of [unreadable]- secretase complex and responsible for intramembranous ..
  31. Regina M Murphy; Fiscal Year: 2016
    ..Transgenic mice that overexpress TTR in astrocytes on an APP/PS1 background will be generated, and pathological endpoints will be evaluated to ascertain the level of in vivo ..
  32. Huaxi Xu; Fiscal Year: 2016
    ..In preliminary studies we demonstrate that APP regulates intracellular trafficking of presenilin 1 (PS1), a critical component of the ?-secretase complex...
  33. Elizabeth M Hillman; Fiscal Year: 2016
    ..expressing fluorescent proteins, and intrinsically fluorescent substrates of energy metabolism such as NADH and FAD. We propose to refine and apply our imaging tools to address the following two fundamentally important questions: &..
  34. Michael S Wolfe; Fiscal Year: 2014
    ..for ?-secretase carrying familial AD mutations? (3) What is the potency and selectivity of Notch-sparing GSIs for PS1 vs...
  35. Neil W Kowall; Fiscal Year: 2014
    ..potential substrates for LSD1, a key enzyme regulating protein methylation that shares considerable homology with FAD-dependent polyamine oxidases...
  36. Comparative effectiveness of Brain Imaging and Blood Biomarkers in Alzheimer??s d
    Orly Lazarov; Fiscal Year: 2010
    ..For example, in transgenic mice harboring FAD- linked mutant APPswe/PS1?E9 onset of amyloid deposition is 4-5 months of age and cognitive deficits are apparent at 8-9 months, while ..
  37. Huaxi Xu; Fiscal Year: 2015
    ..Furthermore, the AD-like pathologies of the APP/PS1/tau triple transgenic AD mice were ameliorated and levels of synaptic marker proteins were increased after crossing ..
  38. Elizabeth R Jacobs; Fiscal Year: 2016
    ..metabolic coenzymes Nicotinamide Adenine Dinucleotide (reduced form is NADH) and Flavine Adenine Dinucleotide (FAD) are the primary electron carriers in oxidative phosphorylation...
  39. Beta Amyloid and Oxidative Stress in Alzheimer's Disease
    Linda J Van Eldik; Fiscal Year: 2012
    ..assembled AB and non-toxic scrambled AB for cell culture experiments, and 3) an Animal Core that will supply APP/PS1 knock-in mutant mice and WT mice, and primary rodent cortical neuron cultures for projects...
  40. Doo Yeon Kim; Fiscal Year: 2016
    ..Our preliminary data indicate that increased BACE1- and PS1/y-secretase-mediated processing of 02 regulates VGSC a-subunit NaJ...
  41. CutA interacts with BACE1 and participates in Alzheimer's disease
    Yunwu Zhang; Fiscal Year: 2012
    ..Moreover, we will use an adeno-associated virus system to deliver CutA into the brains of APP/PS1/tau triple transgenic AD mice and study whether overexpression of CutA can reduce A? plaques and tau tangles, as ..
  42. CD36 in Alzheimer's Disease
    JOSEPH EL-KHOURY; Fiscal Year: 2012
    ..To determine the exact role of CD36-Abeta interactions in the pathogenesis of AD, we bred CD36-/- mice with PS1-APP double transgenic mice that develop accelerated AD-like pathology...
  43. GD3 synthase gene therapy to improve memory and prevent neurodegeneration
    Michael P McDonald; Fiscal Year: 2013
    ..and prevents memory deficits in mice carrying mutant human transgenes for amyloid precursor protein (App) and presenilin 1 (Psen1)...
  44. Sangram S Sisodia; Fiscal Year: 2016
    ..Inheritance of mutated PSEN1 and PSEN2 genes, encoding presenilin 1 and presenilin 2 (PS1 and PS2) variants, respectively, cause early-onset, autosomal dominant forms of familial ..
  45. Zeiss 2-photon (2P) LSM780 laser scanning confocal microscope
    Moshe Levi; Fiscal Year: 2013
    ..Dynamic imaging of metabolism is achieved in part through monitoring changes in NAD(P)H and FAD lifetimes...
  46. Abeta and Monoaminergic Neurodegeneration in Transgenic Mouse Models of AD
    Michael K Lee; Fiscal Year: 2013
    ..We found that, in the APPswe/PS1?E9 Tg mice, A?-deposition is associated with degeneration of monoaminergic (MAergic) systems...
  47. Cations and ROS in Modulating Mitochondrial Function in Normal and Ischemic Heart
    Ranjan K Dash; Fiscal Year: 2013
    ..bioenergetics and electrophysiology (changes in trans-matrix cation concentrations and fluxes, NADH and FAD redox states, membrane potential, respiration, and ROS production with normal and abnormal perturbations in extra-..
  48. REGULATION OF THE APP/NOTCH GAMMA SECRETASE
    Bruce Yankner; Fiscal Year: 2003
    ..Presenilin-1 (PS1) mutations that cause familial Alzheimer's disease alter the gamma-secretase cleavage of APP...
  49. Cognitive Effects of Intracellular Targeted and FAD-linked Mutant Amyloid Betas
    CHRISTOPHER GEORGE JANUS; Fiscal Year: 2012
    ..processes in AD dementia, then CNS expression of internal A[unreadable] mutations that cause familial AD (FAD) should also produce a greater degree of cognitive dysfunction in mouse models then expression of wt A[unreadable]...
  50. John R Cirrito; Fiscal Year: 2014
    ..MIE studies demonstrate brain interstitial fluid (ISF) A[unreadable] levels change from minute-to-minute in APP/PS1 transgenic mice...
  51. Mechanisms Underlying the Vascular Pathology of Alzheimer's Disease
    Gregory A Elder; Fiscal Year: 2012
    ..disease (AD) occur sporadically, some are inherited in an autosomal dominant fashion and known as familial AD (FAD)...
  52. Nikolaos K Robakis; Fiscal Year: 2016
    ..are mediated by their receptors (EphB receptors, EphBRs) and depend on PS1, a protein involved in familial AD (FAD)...
  53. Orly Lazarov; Fiscal Year: 2016
    ..Mutations in the gene encoding PS1 cause Familial Alzheimer's disease (FAD). Recent evidence suggests that PS1 plays a role in adult neurogenesis...
  54. PATHOGENIC MECHANISMS OF PRESENILIN MUTATION
    Robert Siman; Fiscal Year: 2012
    ..and the [unreadable]-amyloid precursor protein (APP) are the leading cause of familial Alzheimer's disease (FAD)...
  55. Tina M Iverson; Fiscal Year: 2016
    ..These include a covalently-bound FAD cofactor, three distinct iron- sulfur clusters, a membrane-bound quinone, and a b heme cofactor...
  56. Alzheimer Mouse Model for Intraneuronal Amyloid-Beta Oligomer Biology
    Samuel E Gandy; Fiscal Year: 2012
    ..we have crossed the Thy1- Dutch APPE693Q mice with familial Alzheimer's mutant presenilin lacking exon 9 (PS1[unreadable]9)...
  57. Cell Biology of Presenilin 1 and Associated Proteins
    Gopal Thinakaran; Fiscal Year: 2012
    ..gamma-secretase is a multimeric protein complex made of four main subunits, namely PS1 (or PS2), nicastrin, PEN2 and APH-1, and a few regulatory subunits including CD147 and p23 (also referred to ..
  58. Elizabeth M Hillman; Fiscal Year: 2015
    ..We will also map fluctuations in flavoprotein (FAD) autofluorescence with spontaneous hemodynamics as a measure of local oxidative metabolism, both complemented with ..
  59. Anti-inflammatory regulation of beta-amyloidosis
    Tsuneya Ikezu; Fiscal Year: 2010
    ..and A[unreadable] oligomer accumulation, and improves cognitive function in a double transgenic mice (APP/PS1) expressing APP and presenilin-1 (PS1)...
  60. Intrinsic fluorescence to guide characterization and purification of stem cells
    Brenda M Ogle; Fiscal Year: 2010
    ..We hypothesize and have preliminary data to suggest that intrinsic metabolic signatures (i.e., NADH, FAD) can serve as noninvasive biomarkers of stem cells when detected with multiphoton optical based approaches...
  61. Stephen M Strittmatter; Fiscal Year: 2015
    ..Encouragingly, the treatment of aged, memory-impaired APP/PS1 mice with anti-PrPC antibody reverses memory deficits...
  62. Intravital Imaging of Stromal and Metabolic Changes in Mammary Tumors
    Pamela A Young; Fiscal Year: 2011
    ..we will collect fluorescence lifetime signatures of the intrinsically fluorescent metabolic co-factors, NADH and FAD, which are known to change based on the microenvironment of the cells...
  63. UTE MRI of Alzheimer's Mice
    Theodore P Trouard; Fiscal Year: 2012
    ..will be developed on a 7T small animal MRI instrument and evaluated in experiments on phantoms and on the brains of PS1/APP double transgenic mice, a common mouse model of Alzheimer's Disease...
  64. DiosMemTM, a natural gamma-secretase inhibitor, opposes AD pathogenesis
    Jun Tan; Fiscal Year: 2009
    ..Importantly, this reduction in GSK-3 activation increases phosphorylation of presenilin 1 (PS1), which forms the catalytic core of the ?-secretase complex, and may suggest a mechanism whereby these ..
  65. Peripheral Biomarkers in Familial Alzheimer's Disease
    Paul Coleman; Fiscal Year: 2009
    ..In this proposal we focus largely on the mutated gene for PS1 since it is a frequently mutated gene among the FAD gene mutations...
  66. Cloning of Late-onset Alzheimer's Disease Genes
    Gerard Schellenberg; Fiscal Year: 2007
    ..Inthesefamilies, offspring of affected personsare at least at 50% risk of inheriting a familial ad (FAD)gene and developing AD. Late-onset FAD(LOFAD) appearsto involve othergenes andisa more complex disease...
  67. FAA AND FAD GENES AND PROTEINS
    Manuel Buchwald; Fiscal Year: 1999
    ..and confirmed its identity by the identification of mutations in FA-A cells; he also has a strong candidate for the FAD gene...
  68. STRUCTURAL DETERMINANTS OF FAD and FMN-REQUIRING ENZYMES
    Bettie Sue Masters; Fiscal Year: 2005
    This proposal emanates from the interests of the Principal Investigator in flavoproteins containing both FAD and FMN as prosthetic groups, extending from her early studies on NADPI-I-cytochrome P450 reductase (CYPOR) to the three nitric ..
  69. Untangling Amyloid Plaques With Proteases
    Jin Moo Lee; Fiscal Year: 2010
    ..MMP-9 immunoreactivity is seen in reactive astrocytes surrounding amyloid plaques of aged APP/PS1 mice...
  70. Structure/Mechanism of an FMN- and FAD-containing Enzyme
    Jung Ja Kim; Fiscal Year: 2005
    ..CYPOR) and nitric oxide synthase isoforms (NOSs) are mammalian enzymes that contain two flavins, FMN and FAD, and an NADPH-binding site...
  71. SENSORY TRANSDUCTION IN BACTERIA
    Barry L Taylor; Fiscal Year: 2011
    ..An N-terminal PAS domain has a FAD cofactor and senses redox and energy level in the cytoplasm...
  72. Thermodynamic Properties of NADH:Nitrate Reductase
    Michael Barber; Fiscal Year: 2005
    ..structure with individual subunits comprising functional domains that contain Mo-pterin, cytochrome b557 and FAD prosthetic groups in a 1:1:1 stoichiometry with FAD as the site of electron ingress and Mo-pterin as the egress ..