Prnp

Summary

Gene Symbol: Prnp
Description: prion protein
Alias: AA960666, AI325101, CD230, PrP, PrP, PrPC, PrPSc, Prn-i, Prn-p, Sinc, prP27-30, prP33-35C, major prion protein
Species: mouse

Top Publications

  1. ncbi Novel proteinaceous infectious particles cause scrapie
    S B Prusiner
    Science 216:136-44. 1982
  2. doi Axonal prion protein is required for peripheral myelin maintenance
    Juliane Bremer
    Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    Nat Neurosci 13:310-8. 2010
  3. pmc Generating a prion with bacterially expressed recombinant prion protein
    Fei Wang
    Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, OH 43210, USA
    Science 327:1132-5. 2010
  4. pmc Cellular prion protein regulates beta-secretase cleavage of the Alzheimer's amyloid precursor protein
    Edward T Parkin
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, United Kingdom
    Proc Natl Acad Sci U S A 104:11062-7. 2007
  5. pmc Prion protein attenuates excitotoxicity by inhibiting NMDA receptors
    Houman Khosravani
    Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, Calgary T2N4N1, Canada
    J Cell Biol 181:551-65. 2008
  6. ncbi 129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal
    J C Manson
    Institute for Animal Health, Edinburgh
    Mol Neurobiol 8:121-7. 1994
  7. ncbi In vitro conversion of full-length mammalian prion protein produces amyloid form with physical properties of PrP(Sc)
    Olga V Bocharova
    Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA
    J Mol Biol 346:645-59. 2005
  8. ncbi Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein
    H Bueler
    Institut für Molekularbiologie I, Universitat Zurich, Switzerland
    Nature 356:577-82. 1992
  9. ncbi Calpain-dependent endoproteolytic cleavage of PrPSc modulates scrapie prion propagation
    Rajgopal Yadavalli
    Department of Microbiology, University of Kentucky, Lexington, Kentucky 40536, USA
    J Biol Chem 279:21948-56. 2004
  10. pmc A nine amino acid domain is essential for mutant prion protein toxicity
    Laura Westergard
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 31:14005-17. 2011

Research Grants

  1. Reconstitution of Prion Transmission in Cells
    Ilia Baskakov; Fiscal Year: 2003
  2. Reconstitution of Prion Infectivity
    Ilia Baskakov; Fiscal Year: 2005
  3. Experimental Creutzfeldt Jacob Disease
    Laura Manuelidis; Fiscal Year: 2007
  4. Therapeutic Monoclonal Antibodies for Human Prion Diseases
    MARTIN JOSEPH SADOWSKI; Fiscal Year: 2010

Detail Information

Publications220 found, 100 shown here

  1. ncbi Novel proteinaceous infectious particles cause scrapie
    S B Prusiner
    Science 216:136-44. 1982
    ..Knowledge of the scrapie agent structure may have significance for understanding the causes of several degenerative diseases...
  2. doi Axonal prion protein is required for peripheral myelin maintenance
    Juliane Bremer
    Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    Nat Neurosci 13:310-8. 2010
    ..Here we show that ablation of the prion protein PrP(C) triggers a chronic demyelinating polyneuropathy (CDP) in four independently targeted mouse strains...
  3. pmc Generating a prion with bacterially expressed recombinant prion protein
    Fei Wang
    Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, OH 43210, USA
    Science 327:1132-5. 2010
    The prion hypothesis posits that a misfolded form of prion protein (PrP) is responsible for the infectivity of prion disease...
  4. pmc Cellular prion protein regulates beta-secretase cleavage of the Alzheimer's amyloid precursor protein
    Edward T Parkin
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, United Kingdom
    Proc Natl Acad Sci U S A 104:11062-7. 2007
    ..The normal cellular function of the prion protein (PrP(C)), the causative agent of the transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease in ..
  5. pmc Prion protein attenuates excitotoxicity by inhibiting NMDA receptors
    Houman Khosravani
    Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, Calgary T2N4N1, Canada
    J Cell Biol 181:551-65. 2008
    It is well established that misfolded forms of cellular prion protein (PrP [PrP(C)]) are crucial in the genesis and progression of transmissible spongiform encephalitis, whereas the function of native PrP(C) remains incompletely ..
  6. ncbi 129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal
    J C Manson
    Institute for Animal Health, Edinburgh
    Mol Neurobiol 8:121-7. 1994
    The neural membrane glycoprotein PrP is implicated in the pathogenesis of the transmissible spongiform encephalopathies; however, the normal function of PrP and its precise role in disease are not understood...
  7. ncbi In vitro conversion of full-length mammalian prion protein produces amyloid form with physical properties of PrP(Sc)
    Olga V Bocharova
    Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA
    J Mol Biol 346:645-59. 2005
    The "protein only" hypothesis postulates that the infectious agent of prion diseases, PrP(Sc), is composed of the prion protein (PrP) converted into an amyloid-specific conformation...
  8. ncbi Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein
    H Bueler
    Institut für Molekularbiologie I, Universitat Zurich, Switzerland
    Nature 356:577-82. 1992
    b>PrPC is a host protein anchored to the outer surface of neurons and to a lesser extent of lymphocytes and other cells. The transmissible agent (prion) responsible for scrapie is believed to be a modified form of PrPC...
  9. ncbi Calpain-dependent endoproteolytic cleavage of PrPSc modulates scrapie prion propagation
    Rajgopal Yadavalli
    Department of Microbiology, University of Kentucky, Lexington, Kentucky 40536, USA
    J Biol Chem 279:21948-56. 2004
    Previous studies using post-mortem human brain extracts demonstrated that PrP in Creutzfeldt-Jakob disease (CJD) brains is cleaved by a cellular protease to generate a C-terminal fragment, referred to as C2, which has the same molecular ..
  10. pmc A nine amino acid domain is essential for mutant prion protein toxicity
    Laura Westergard
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 31:14005-17. 2011
    Transgenic mice expressing prion protein (PrP) molecules with several different internal deletions display spontaneous neurodegenerative phenotypes that can be dose-dependently suppressed by coexpression of wild-type PrP...
  11. ncbi Chronic lymphocytic inflammation specifies the organ tropism of prions
    Mathias Heikenwalder
    Institute of Neuropathology, University Hospital of Zurich, CH 8091 Zurich, Switzerland
    Science 307:1107-10. 2005
    ..inflamed organs of mice lacking lymphotoxin-alpha or its receptor did not accumulate the abnormal isoform PrPSc, nor did they display infectivity upon prion inoculation...
  12. pmc Male infertility and DNA damage in Doppel knockout and prion protein/Doppel double-knockout mice
    Derek Paisley
    Molecular Medicine Centre, University of Edinburgh, Edinburgh, Scotland
    Am J Pathol 164:2279-88. 2004
    ..To test this hypothesis and also investigate the function of Dpl we have generated Prnd(-/-) and Prnp(-/-)/Prnd(-/-) mouse lines...
  13. doi Lymphotoxin-dependent prion replication in inflammatory stromal cells of granulomas
    Mathias Heikenwalder
    Institute of Neuropathology, Department of Pathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH 8091 Zurich, Switzerland
    Immunity 29:998-1008. 2008
    ..that soft-tissue granulomas, a frequent feature of chronic inflammation, expressed the cellular prion protein (PrPC, encoded by Prnp) and the lymphotoxin receptor (LTbetaR), even though they lacked FDCs and did not display ..
  14. pmc Fatal transmissible amyloid encephalopathy: a new type of prion disease associated with lack of prion protein membrane anchoring
    Bruce Chesebro
    Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, United States of America
    PLoS Pathog 6:e1000800. 2010
    ..deposited in brain in an amyloid-form and/or non-amyloid form, and is derived from host-encoded protease-sensitive PrP (PrPsen), a protein normally anchored to the plasma membrane by glycosylphosphatidylinositol (GPI)...
  15. ncbi Synthetic mammalian prions
    Giuseppe Legname
    Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
    Science 305:673-6. 2004
    ..Brain extracts showed protease-resistant PrP by Western blotting; these extracts transmitted disease to wild-type FVB mice and Tg mice overexpressing PrP, with ..
  16. pmc Expression of mutant or cytosolic PrP in transgenic mice and cells is not associated with endoplasmic reticulum stress or proteasome dysfunction
    Elena Quaglio
    Dulbecco Telethon Institute, Milan, Italy
    PLoS ONE 6:e19339. 2011
    The cellular pathways activated by mutant prion protein (PrP) in genetic prion diseases, ultimately leading to neuronal dysfunction and degeneration, are not known...
  17. doi The cellular prion protein identifies bipotential cardiomyogenic progenitors
    Kyoko Hidaka
    Department of Bioscience, National Cardiovascular Center Research Institute, Suita, Osaka, Japan
    Circ Res 106:111-9. 2010
    ..Identification of relevant surface markers may also enhance our understanding of the mechanisms underlying differentiation...
  18. pmc Low density subcellular fractions enhance disease-specific prion protein misfolding
    James F Graham
    Neuropathogenesis Division, The Roslin Institute and Royal Dick School of Veterinary Studies, University of Edinburgh, Alexander Robertson Building, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK
    J Biol Chem 285:9868-80. 2010
    ..with or without exogenous seed typically results in infectivity titers less than those associated with PrP(Sc) isolated ex vivo and highlights the potential role of co-factors that can catalyze disease-specific prion ..
  19. pmc Lymph nodal prion replication and neuroinvasion in mice devoid of follicular dendritic cells
    Marco Prinz
    Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH 8091 Zurich, Switzerland
    Proc Natl Acad Sci U S A 99:919-24. 2002
    ..Transfer of TNFR1(-/-) fetal liver cells into lethally irradiated Prnp(0/0) mice restored infectivity mainly in lymph nodes...
  20. pmc Single treatment with RNAi against prion protein rescues early neuronal dysfunction and prolongs survival in mice with prion disease
    Melanie D White
    Department of Neurodegenerative Disease, Medical Research Council, Prion Unit Institute of Neurology, University College London, London, United Kingdom
    Proc Natl Acad Sci U S A 105:10238-43. 2008
    ..Prion propagation involves the conversion of cellular prion protein, PrP(C), to its conformational isomer, PrP(Sc), which accumulates in disease...
  21. pmc Prion protein misfolding affects calcium homeostasis and sensitizes cells to endoplasmic reticulum stress
    Mauricio Torres
    Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
    PLoS ONE 5:e15658. 2010
    ..well as the accumulation of an abnormally folded and protease resistant form of the cellular prion protein, termed PrP(RES)...
  22. ncbi Packaging of prions into exosomes is associated with a novel pathway of PrP processing
    L J Vella
    Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria 3010, Australia
    J Pathol 211:582-90. 2007
    ..are fatal, transmissible neurodegenerative disorders associated with conversion of the host-encoded prion protein (PrP(C)) into an abnormal pathogenic isoform (PrP(Sc))...
  23. pmc Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie
    M Fischer
    Institut für Molekularbiologie der Universität Zürich, Switzerland
    EMBO J 15:1255-64. 1996
    ..only' hypothesis postulates that the prion, the agent causing transmissible spongiform encephalopathies, is PrP(Sc), an isoform of the host protein PrP(C)...
  24. pmc Normal host prion protein (PrPC) is required for scrapie spread within the central nervous system
    S Brandner
    Institute of Neuropathology, University Hospital, Zurich, Switzerland
    Proc Natl Acad Sci U S A 93:13148-51. 1996
    ..Neither encephalopathy nor protease-resistant PrP (PrPSc) were detected in the grafts for up to 66 weeks...
  25. ncbi Imbalance of antioxidant defense in mice lacking cellular prion protein
    F Klamt
    Laboratório de Estresse Oxidativo, Departamento de Bioquimica, ICBS Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
    Free Radic Biol Med 30:1137-44. 2001
    ..disorders resulting from conformational changes in the prion protein from its normal cellular isoform, PrPC, to the infectious scrapie isoform, PrP(Sc)...
  26. ncbi The prion protein gene: a role in mouse embryogenesis?
    J Manson
    Institute for Animal Health, AFRC, Edinburgh, UK
    Development 115:117-22. 1992
    The neural membrane glycoprotein PrP (prion protein) has a key role in the development of scrapie and related neurodegenerative diseases...
  27. ncbi A cellular gene encodes scrapie PrP 27-30 protein
    B Oesch
    Cell 40:735-46. 1985
    A clone encoding PrP 27-30, the major protein in purified preparations of scrapie agent, was selected from a scrapie-infected hamster brain cDNA library by oligonucleotide probes corresponding to the N terminus of the protein...
  28. ncbi Folding intermediates of the prion protein stabilized by hydrostatic pressure and low temperature
    Samantha M Martins
    Departamento de Bioquimica Medica, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941 590, Brazil
    J Biol Chem 278:50449-55. 2003
    ..diseases are associated with conformational conversion of the cellular prion protein, PrPC, into a misfolded form, PrPSc. We have investigated the equilibrium unfolding of the structured domain of recombinant murine prion protein, ..
  29. ncbi Dynamics and local ordering of spin-labeled prion protein: an ESR simulation study of a highly PH-sensitive site
    Yun Wei Chiang
    Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan
    J Biomol Struct Dyn 26:355-66. 2008
    ..It suggests a more mobile and disordered dynamic molecular structure for mouse PrPC, which is very likely correlated with increased beta-sheet content at low pH, as the environment changes from ..
  30. doi Mutant prion protein expression causes motor and memory deficits and abnormal sleep patterns in a transgenic mouse model
    Sara Dossena
    Dulbecco Telethon Institute, 20156 Milan, Italy Department of Neuroscience, Mario Negri Institute for Pharmacological Research, 20156 Milan, Italy
    Neuron 60:598-609. 2008
    A familial form of Creutzfeldt-Jakob disease (CJD) is linked to the D178N/V129 prion protein (PrP) mutation...
  31. pmc Pharmacological prion protein silencing accelerates central nervous system autoimmune disease via T cell receptor signalling
    Wei Hu
    Department of Neurology, University of Texas Southwestern Medical Center at Dallas, TX, USA
    Brain 133:375-88. 2010
    ..Our data identify cellular prion protein as a regulator of cellular immunological homoeostasis and suggest cellular prion protein as a novel potential target for therapeutic immunomodulation...
  32. doi Copper(II)-induced secondary structure changes and reduced folding stability of the prion protein
    Nadine D Younan
    School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK
    J Mol Biol 410:369-82. 2011
    The cellular isoform of the prion protein PrP(C) is a Cu(2)(+)-binding cell surface glycoprotein that, when misfolded, is responsible for a range of transmissible spongiform encephalopathies...
  33. pmc The N-terminal, polybasic region is critical for prion protein neuroprotective activity
    Jessie A Turnbaugh
    Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts, United States of America
    PLoS ONE 6:e25675. 2011
    Several lines of evidence suggest that the normal form of the prion protein, PrP(C), exerts a neuroprotective activity against cellular stress or toxicity...
  34. pmc Prion protein and Shadoo are involved in overlapping embryonic pathways and trophoblastic development
    Bruno Passet
    INRA, UMR1313, Génétique Animale et Biologie Intégrative, INRA, Jouy en Josas, France
    PLoS ONE 7:e41959. 2012
    ..In the present study, using various Prnp transgenic mouse lines and lentiviral vectors expressing shRNAs that target the Shadoo-encoding mRNA, we further ..
  35. doi Developmental expression of prion protein and its ligands stress-inducible protein 1 and vitronectin
    Glaucia N M Hajj
    Ludwig Institute for Cancer Research, São Paulo 01323 903, Brazil
    J Comp Neurol 517:371-84. 2009
    Prion protein (PrP(C)) is the normal isoform of PrP(Sc), a protein involved in neurodegenerative disorders...
  36. doi The prion or the related Shadoo protein is required for early mouse embryogenesis
    Rachel Young
    INRA UMR1313, Génétique Animale et Biologie Intégrative, Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France
    FEBS Lett 583:3296-300. 2009
    The prion protein PrP has a key role in transmissible spongiform encephalopathies but its biological function remains largely unknown. Recently, a related protein, Shadoo, was discovered...
  37. pmc Expression and knockdown of cellular prion protein (PrPC) in differentiating mouse embryonic stem cells
    Oscar A Peralta
    Department of Large Animal Clinical Sciences, Virginia Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061 0442, USA
    Differentiation 81:68-77. 2011
    The mammalian cellular prion protein (PrP(C)) is a highly conserved glycoprotein that may undergo conversion into a conformationally altered isoform (scrapie prion protein or PrP(Sc)), widely believed to be the pathogenic agent of ..
  38. pmc A versatile prion replication assay in organotypic brain slices
    Jeppe Falsig
    Institute of Neuropathology, University of Zurich, Schmelzbergstrasse 12, Zurich, Switzerland
    Nat Neurosci 11:109-17. 2008
    ..days after contact with prions, mouse cerebellar slices had amplified the abnormal isoform of prion protein, PrP(Sc), >10(5)-fold. This is quantitatively similar to amplification in vivo, but fivefold faster...
  39. pmc Dominant-negative effects of the N-terminal half of prion protein on neurotoxicity of prion protein-like protein/doppel in mice
    Daisuke Yoshikawa
    Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, 1 12 4 Sakamoto, Nagasaki
    J Biol Chem 283:24202-11. 2008
    ..We also show that prion protein lacking the pre-octapeptide repeat (Delta25-50) or octapeptide repeat (Delta51-90) region alone could not impair the antagonistic function against doppel...
  40. pmc Stress-protective signalling of prion protein is corrupted by scrapie prions
    Angelika S Rambold
    Department of Biochemistry, Neurobiochemistry, Ludwig Maximilians University Munich, Munchen, Germany
    EMBO J 27:1974-84. 2008
    Studies in transgenic mice revealed that neurodegeneration induced by scrapie prion (PrP(Sc)) propagation is dependent on neuronal expression of the cellular prion protein PrP(C)...
  41. pmc Absence of the cellular prion protein exacerbates and prolongs neuroinflammation in experimental autoimmune encephalomyelitis
    Shigeki Tsutsui
    Department of Biochemistry and Molecular Biology, McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada
    Am J Pathol 173:1029-41. 2008
    Although the physiological roles of the cellular prion protein (PrP C) remain to be fully elucidated, PrP C has been proposed to represent a potential regulator of cellular immunity...
  42. doi alpha-cleavage of the prion protein occurs in a late compartment of the secretory pathway and is independent of lipid rafts
    Adrian R Walmsley
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS29JT, UK
    Mol Cell Neurosci 40:242-8. 2009
    Endoproteolysis of the cellular prion protein (PrP(C)) modulates both the normal function of the protein and the pathogenesis of the neurodegenerative prion diseases...
  43. pmc Accumulation of proteinase K-resistant prion protein (PrP) is restricted by the expression level of normal PrP in mice inoculated with a mouse-adapted strain of the Creutzfeldt-Jakob disease agent
    S Sakaguchi
    Department of Bacteriology, Nagasaki University School of Medicine, Japan
    J Virol 69:7586-92. 1995
    ..To determine whether there was an involvement of the host-encoded prion protein (PrPc) in CJD development and prion propagation, mice heterozygous (PrP+/-) or homozygous (PrP-/-) for a disrupted PrP ..
  44. pmc Expression of truncated PrP targeted to Purkinje cells of PrP knockout mice causes Purkinje cell death and ataxia
    Eckhard Flechsig
    Institut fur Molekularbiologie, Universitat Zurich, CH 8057 Zurich, Switzerland
    EMBO J 22:3095-101. 2003
    b>PrP knockout mice with disruption of only the PrP-encoding region (Zürich I-type) remain healthy, whereas mice with deletions extending upstream of the PrP-encoding exon (Nagasaki-type) suffer Purkinje cell loss and ataxia, associated ..
  45. ncbi Anchorless prion protein results in infectious amyloid disease without clinical scrapie
    Bruce Chesebro
    Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA
    Science 308:1435-9. 2005
    ..In scrapie-infected transgenic mice expressing prion protein (PrP) lacking the glycosylphosphatidylinositol (GPI) membrane anchor, abnormal protease-resistant PrPres was deposited ..
  46. ncbi Early detection of PrPres in BSE-infected bovine PrP transgenic mice
    J Castilla
    Centro de Investigacion en Sanidad Animal, INIA, Madrid, Spain
    Arch Virol 148:677-91. 2003
    ..Typical CNS spongiform degeneration was observed by histopathology and presence of PrP(res) could be detected both by Western blot and immunohistochemistry (IHC) assays, confirming for this model the ..
  47. ncbi Expression of Prnp mRNA (prion protein gene) in mouse spermatogenic cells
    Masahiko Fujisawa
    Department of Veterinary Anatomy, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi, Bunkyo ku, Japan
    J Reprod Dev 50:565-70. 2004
    The Prnp (prion protein) gene, which encodes a soluble protein anchored to the cell surface by glycosylphosphatidylinositol (GPI), might be involved in cell-to-cell interaction...
  48. ncbi Scrapie infection of prion protein-deficient cell line upon ectopic expression of mutant prion proteins
    Elke Maas
    Institute of Virology, Technical University of Munich, Troger Strasse 30, 81675 Munich, Germany
    J Biol Chem 282:18702-10. 2007
    Expression of the cellular prion protein (PrP(C)) is crucial for susceptibility to prions...
  49. pmc Dynamics of a truncated prion protein, PrP(113-231), from (15)N NMR relaxation: order parameters calculated and slow conformational fluctuations localized to a distinct region
    Denis B D O'Sullivan
    Queen Mary University of London, United Kingdom
    Protein Sci 18:410-23. 2009
    Prion diseases are associated with the misfolding of the prion protein (PrP(C)) from a largely alpha-helical isoform to a beta-sheet rich oligomer (PrP(Sc))...
  50. doi A role of cellular prion protein in programming T-cell cytokine responses in disease
    Rebecca J Ingram
    Dept of Infectious Diseases and Immunity, Imperial College London, Hammersmith Hospital, Du Cane Rd, London W12 0NN, UK
    FASEB J 23:1672-84. 2009
    ..yet the functional significance of this activation remains unclear, with conflicting data on the effects of Prnp gene knockout on various parameters of T-cell immunity...
  51. doi New insights into cellular prion protein (PrPc) functions: the "ying and yang" of a relevant protein
    Oriol Nicolas
    Molecular and Cellular Neurobiotechnology laboratory, Catalonian Bioengineering Institute IBEC, Baldiri Reixac 15 21, and Department of Cell Biology, University of Barcelona, Barcelona, Spain
    Brain Res Rev 61:170-84. 2009
    The conversion of cellular prion protein (PrP(c)), a GPI-anchored protein, into a protease-K-resistant and infective form (generally termed PrP(sc)) is mainly responsible for Transmissible Spongiform Encephalopathies (TSEs), ..
  52. pmc Unexpected tolerance of alpha-cleavage of the prion protein to sequence variations
    José B Oliveira-Martins
    Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    PLoS ONE 5:e9107. 2010
    The cellular form of the prion protein, PrP(C), undergoes extensive proteolysis at the alpha site (109K [see text]H110)...
  53. pmc Prion protein-deficient neurons reveal lower glutathione reductase activity and increased susceptibility to hydrogen peroxide toxicity
    A R White
    Department of Pathology, University of Melbourne, Melbourne, Australia
    Am J Pathol 155:1723-30. 1999
    The prion protein (PrP) has a central role in the pathogenesis of transmissible spongiform encephalopathies (TSE)...
  54. pmc Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8
    Jan Kranich
    Institute of Neuropathology, University Hospital of Zurich, 8091 Zurich, Switzerland
    J Exp Med 205:1293-302. 2008
    ..Lymphotoxin-deficient mice lacked FDCs and splenic Mfge8, and suffer from autoimmunity similar to Mfge8(-/-) mice. Hence, FDCs facilitate TBMphi-mediated corpse removal, and their malfunction may be involved in autoimmunity...
  55. pmc De novo generation of a transmissible spongiform encephalopathy by mouse transgenesis
    Christina J Sigurdson
    Universitatsspital Zurich, Institute of Neuropathology, CH 8091 Zurich, Switzerland
    Proc Natl Acad Sci U S A 106:304-9. 2009
    Most transmissible spongiform encephalopathies arise either spontaneously or by infection. Mutations of PRNP, which encodes the prion protein, PrP, segregate with phenotypically similar diseases...
  56. pmc Localization of the human gene allowing infection by gibbon ape leukemia virus to human chromosome region 2q11-q14 and to the homologous region on mouse chromosome 2
    M Kaelbling
    Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461
    J Virol 65:1743-7. 1991
    ..This mouse chromosome carries Rec-2, the likely receptor for M813, a retrovirus derived from a feral Asian mouse. These data raise the interesting possibility that Rec-2 and Glvr-1 are structurally related...
  57. pmc Identification of two prion protein regions that modify scrapie incubation time
    S Supattapone
    Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94143, USA
    J Virol 75:1408-13. 2001
    ..with Rocky Mountain Laboratory (RML) murine prions, scrapie incubation times for Tg(MoPrP)4053, Tg(MHM2)294/Prnp(0/0), and Tg(MoPrP, Delta23-88)9949/Prnp(0/0) mice were approximately 50, 120, and 160 days, respectively...
  58. ncbi Involvement of cellular prion protein in the nociceptive response in mice
    Flavia Carla Meotti
    Departamento de Quimica, Universidade Federal de Santa Maria, Santa Maria, RS, 97110 000, Brasil
    Brain Res 1151:84-90. 2007
    ..Here we investigated the putative involvement of the PrP(c) function on the nociceptive response using PrP(c) null (Prnp(0/0)) and wild-type (Prnp(+/+)) mice submitted to thermal and chemical models of nociception...
  59. ncbi Overexpression of cellular prion protein alters postischemic Erk1/2 phosphorylation but not Akt phosphorylation and protects against focal cerebral ischemia
    Jens Weise
    Department of Neurology, University of Jena Medical School, 07747 Jena, Germany
    Restor Neurol Neurosci 26:57-64. 2008
    The physiological function of the cellular prion protein (PrPC) is still unclear. A growing body of evidence suggests that PrPC has neuroprotective properties and that its deletion increases susceptibility to focal cerebral ischemia...
  60. pmc Identifying key components of the PrPC-PrPSc replicative interface
    Gil C Abalos
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 283:34021-8. 2008
    In prion disease, direct interaction between the cellular prion protein (PrP(C)) and its misfolded disease-associated conformer PrP(Sc) is a crucial, although poorly understood step promoting the formation of nascent PrP(Sc) and prion ..
  61. pmc Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse
    Sead Chadi
    INRA, UMR1313, Génétique Animale et Biologie Intégrative, F 78350, Jouy en Josas, France
    BMC Genomics 11:448. 2010
    ..To potentially assess this conundrum, we performed a comparative transcriptomic analysis of the brain of wild-type mice with that of transgenic mice invalidated at this locus either at the zygotic or at the adult stages...
  62. doi Cellular prion protein localizes to the nucleus of endocrine and neuronal cells and interacts with structural chromatin components
    Alexander Strom
    Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
    Eur J Cell Biol 90:414-9. 2011
    Several physiological processes have been purported for cellular prion protein (PrP(C)). However, the physiological function of PrP(C) is still unclear and the cellular localization of PrP(C) remains a subject of debate...
  63. doi Threshold for epileptiform activity is elevated in prion knockout mice
    S Ratte
    Neuronal Networks Group, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
    Neuroscience 179:56-61. 2011
    Prion protein (PrP) is abundant in the nervous system, but its role remains uncertain. Prion diseases depend on an aggregation of the protein that is likely to interfere with its normal function...
  64. doi Developmental influence of the cellular prion protein on the gene expression profile in mouse hippocampus
    Stefano Benvegnù
    Laboratory of Prion Biology, Scuola Internazionale Superiore di Studi Avanzati SISSA, Trieste
    Physiol Genomics 43:711-25. 2011
    ..5-day-old) and adult (3-mo-old) mice, both from wild-type and Prnp(0/0) animals...
  65. ncbi Prion protein is necessary for normal synaptic function
    J Collinge
    Department of Biochemistry and Molecular Genetics, St Mary s Hospital Medical School, Imperial College, London, UK
    Nature 370:295-7. 1994
    ..consists principally of a post-translationally modified form of a host-encoded glycoprotein (PrPC), designated PrPSc (ref. 1); the normal cellular function of PrPC is, however, unknown...
  66. ncbi Normal host prion protein necessary for scrapie-induced neurotoxicity
    S Brandner
    Department of Pathology, University Hospital, Zurich, Switzerland
    Nature 379:339-43. 1996
    Accumulation of the prion protein PrPSc, a pathological and protease-resistant isoform of the normal host protein PrPC, is a feature of prion disease such as scrapie...
  67. ncbi Altered circadian activity rhythms and sleep in mice devoid of prion protein
    I Tobler
    Institute of Pharmacology, University of Zurich, Switzerland
    Nature 380:639-42. 1996
    There is a wealth of data supporting a central role for the prion protein (PrP) in the neurodegenerative prion diseases of both humans and other species, yet the normal function of PrP, which is expressed at the cell surface of neurons ..
  68. ncbi Prions prevent neuronal cell-line death
    C Kuwahara
    Nature 400:225-6. 1999
  69. ncbi The prion protein requires cholesterol for cell surface localization
    Sabine Gilch
    Institute of Virology, Technical University of Munich, Biedersteiner Str 29, D 80802 Munich, Germany
    Mol Cell Neurosci 31:346-53. 2006
    The cellular prion protein PrP(c) is attached to the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI-) anchor and is localized in lipid rafts, membrane microdomains characterized by a high content of sphingolipids and ..
  70. pmc Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers
    Juha Lauren
    Cellular Neuroscience, Neurodegeneration and Repair Program, Yale University School of Medicine, New Haven, Connecticut 06536, USA
    Nature 457:1128-32. 2009
    ..Here we identify the cellular prion protein (PrP(C)) as an amyloid-beta-oligomer receptor by expression cloning...
  71. pmc Delimiting the location of the scrapie prion incubation time gene on chromosome 2 of the mouse
    G A Carlson
    McLaughlin Research Institute, Great Falls, Montana 59401
    Genetics 133:979-88. 1993
    ..influenced by an incubation time gene (Prn-i) that is linked to Prn-p, the structural gene for prion protein (PrP)...
  72. ncbi NMR structure of the mouse prion protein domain PrP(121-231)
    R Riek
    Institut fur Molekularbiologie und Biophysik, Eidgenossische Technische Hochschule Honggerberg, Zurich, Switzerland
    Nature 382:180-2. 1996
    ..are thought to exist in two different conformations: the 'benign' PrPcform, and the infectious 'scrapie form', PrPsc. Knowledge of the three-dimensional structure of PrPc is essential for understanding the transition to PrPsc...
  73. ncbi Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions
    D Shmerling
    Institut fur Molekularbiologie, Abteilung I, Universitat Zurich, Switzerland
    Cell 93:203-14. 1998
    The physiological role of prion protein (PrP) remains unknown. Mice devoid of PrP develop normally but are resistant to scrapie; introduction of a PrP transgene restores susceptibility to the disease...
  74. ncbi A mouse prion protein transgene rescues mice deficient for the prion protein gene from purkinje cell degeneration and demyelination
    N Nishida
    Department of Bacteriology, Nagasaki University School of Medicine, Japan
    Lab Invest 79:689-97. 1999
    Disruption of both alleles of the prion protein gene, Prnp, renders mice resistant to prions; in a Prnp o/o line reported by some of us, mice progressively developed ataxia and Purkinje cell loss...
  75. pmc Accumulation of protease-resistant prion protein (PrP) and apoptosis of cerebellar granule cells in transgenic mice expressing a PrP insertional mutation
    R Chiesa
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 97:5574-9. 2000
    We have generated lines of transgenic mice that express a mutant prion protein (PrP) containing 14 octapeptide repeats whose human homologue is associated with an inherited prion dementia...
  76. pmc Conversion of raft associated prion protein to the protease-resistant state requires insertion of PrP-res (PrP(Sc)) into contiguous membranes
    Gerald S Baron
    Laboratory of Persistent Viral Diseases, NIAID, NIH, Rocky Mountain Laboratories, 903 South 4th Street, Hamilton, MT 59840, USA
    EMBO J 21:1031-40. 2002
    Prion protein (PrP) is usually attached to membranes by a glycosylphosphatidylinositol-anchor that associates with detergent-resistant membranes (DRMs), or rafts...
  77. pmc Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection
    Silvio M Zanata
    Ludwig Institute for Cancer Research, Sao Paulo Branch, Rua Prof Antônio Prudente 109 4A, São Paulo 01509010, Brasil
    EMBO J 21:3307-16. 2002
    Prions are composed of an isoform of a normal sialoglycoprotein called PrP(c), whose physiological role has been under investigation, with focus on the screening for ligands...
  78. ncbi Stimulation of PrP(C) retrograde transport toward the endoplasmic reticulum increases accumulation of PrP(Sc) in prion-infected cells
    Florence Beranger
    Institut de Genetique Humaine, UPR CNRS1142, 141 rue de la Cardonille, 34396, Montpellier Cedex 5, France
    J Biol Chem 277:38972-7. 2002
    ..disorders characterized by the accumulation of an abnormally folded isoform of the cellular prion protein (PrP(C)) denoted PrP(Sc)...
  79. ncbi Immunologically induced, complement-dependent up-regulation of the prion protein in the mouse spleen: follicular dendritic cells versus capsule and trabeculae
    Marius Lötscher
    Institutes of Experimental Immunology and Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    J Immunol 170:6040-7. 2003
    The expression of the prion protein (PrP) in the follicular dendritic cell network of germinal centers in the spleen is critical for the splenic propagation of the causative agent of prion diseases...
  80. ncbi Prions prevent brain damage after experimental brain injury: a preliminary report
    S Hoshino
    Departament of Neurosurgery, Nippon Medical School, Tokyo, Japan
    Acta Neurochir Suppl 86:297-9. 2003
    The physiological function of the normal cellular form of prion protein (PrPC) is not yet fully understood. In the current study we used prion protein gene knock-out mice (Prnp-/-) to assess the role of PrPC in traumatic brain injury...
  81. ncbi Alpha- and beta- cleavages of the amino-terminus of the cellular prion protein
    Alain Mangé
    Institut de Genetique Humaine, CNRS U P R 1142, 141, rue de la Cardonille, 34396 Montpellier Cedex 5, France
    Biol Cell 96:125-32. 2004
    It is commonly assumed that the physiological isoform of prion protein, PrP(C), is cleaved during its normal processing between residues 111/112, whereas the pathogenic isoform, PrP(Sc), is cleaved at an alternate site in the octapeptide ..
  82. pmc Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth
    Antonella Santuccione
    Zentrum für Molekulare Neurobiologie, Universitat Hamburg, Germany
    J Cell Biol 169:341-54. 2005
    In spite of advances in understanding the role of the cellular prion protein (PrP) in neural cell interactions, the mechanisms of PrP function remain poorly characterized...
  83. pmc Neonatal lethality in transgenic mice expressing prion protein with a deletion of residues 105-125
    Aimin Li
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110, USA
    EMBO J 26:548-58. 2007
    To identify sequence domains important for the neurotoxic and neuroprotective activities of the prion protein (PrP), we have engineered transgenic mice that express a form of murine PrP deleted for a conserved block of 21 amino acids (..
  84. ncbi Reduced erythroid cell and erythropoietin production in response to acute anemia in prion protein-deficient (Prnp-/-) mice
    Jan H Zivny
    1st School of Medicine, Charles University, Prague, Czech Republic
    Blood Cells Mol Dis 40:302-7. 2008
    Cellular prion protein (PrPc) participates in the pathogenesis of prion diseases but its normal function remains unclear. PrPc is expressed on hematopoietic cells, including erythroid precursors...
  85. pmc Host PrP glycosylation: a major factor determining the outcome of prion infection
    Nadia L Tuzi
    Neuropathogenesis Unit, Roslin Institute, Edinburgh, United Kingdom
    PLoS Biol 6:e100. 2008
    The expression of the prion protein (PrP) is essential for transmissible spongiform encephalopathy (TSE) or prion diseases to occur, but the underlying mechanism of infection remains unresolved...
  86. pmc Reduced translocation of nascent prion protein during ER stress contributes to neurodegeneration
    Neena S Rane
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Dev Cell 15:359-70. 2008
    During acute stress in the endoplasmic reticulum (ER), mammalian prion protein (PrP) is temporarily prevented from translocation into the ER and instead routed directly for cytosolic degradation...
  87. doi A deleted prion protein that is neurotoxic in vivo is localized normally in cultured cells
    Heather M Christensen
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurochem 108:44-56. 2009
    The prion protein (PrP) possesses sequence-specific domains that endow the molecule with neuroprotective and neurotoxic activities, and that may contribute to the pathogenesis of prion diseases...
  88. pmc Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time
    G A Carlson
    Jackson Laboratory, Bar Harbor, Maine 04609
    Mol Cell Biol 8:5528-40. 1988
    The mouse prion protein (PrP) gene (Prn-p), which encodes the only macromolecule that has been identified in scrapie prions, is tightly linked or identical to a gene (Prn-i) that controls the duration of the scrapie incubation period in ..
  89. ncbi Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein
    G C Telling
    Department of Neurology, University of California, San Francisco 94143, USA
    Cell 83:79-90. 1995
    ..humans with inherited or sporadic prion disease to investigate the mechanism by which PrPC is transformed into PrPSc. Although Tg(HuPrP) mice expressed high levels of HuPrPC, they were resistant to human prions...
  90. ncbi Mice devoid of PrP are resistant to scrapie
    H Bueler
    Institut für Molekularbiologie I, Universitat Zurich, Switzerland
    Cell 73:1339-47. 1993
    S.B. Prusiner proposed that the infectious agent of scraple, the prion, is PrPSc, a modified form of the normal host protein PrPC. Prn-p0/0 mice devoid of PrPC showed normal development and behavior...
  91. ncbi Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene
    S Sakaguchi
    Department of Bacteriology, Nagasaki University School of Medicine, Nagasaki, Japan
    Nature 380:528-31. 1996
    Prion protein (PrP) is a glycoprotein constitutively expressed on the neuronal cell surface. A protease-resistant isoform of prion protein is implicated in the pathogenesis of a series of transmissible spongiform encephalopathies...
  92. ncbi Heritable disorder resembling neuronal storage disease in mice expressing prion protein with deletion of an alpha-helix
    T Muramoto
    Department of Neurology, University of California, San Francisco 94143, USA
    Nat Med 3:750-5. 1997
    Mice were constructed carrying prion protein (PrP) transgenes with individual regions of putative secondary structure deleted...
  93. pmc Evidence for protein X binding to a discontinuous epitope on the cellular prion protein during scrapie prion propagation
    K Kaneko
    Department of Neurology, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 94:10069-74. 1997
    ..provisionally designated protein X participates in the formation of nascent scrapie isoform of prion protein (PrPSc)...
  94. pmc A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy
    J C Manson
    BBSRC Neuropathogenesis Unit, Institute for Animal Health, Ogston Building, West Mains Road, Edinburgh EH9 3JF
    EMBO J 18:6855-64. 1999
    A mutation equivalent to P102L in the human PrP gene, associated with Gerstmann-Straussler syndrome (GSS), has been introduced into the murine PrP gene by gene targeting...
  95. pmc Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain
    D Rossi
    MRC Prion Unit Neurogenetics, Imperial College School of Medicine at St Mary s, London W2 1PG, UK
    EMBO J 20:694-702. 2001
    ..9 kb PRNP: deletion, developed this phenotype at approximately 10 months (50% morbidity)...
  96. ncbi Increased levels of oxidative stress markers detected in the brains of mice devoid of prion protein
    B S Wong
    Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Neurochem 76:565-72. 2001
    Although minor abnormalities have been reported in prion protein (PrP) knock-out (Prnp-/-) mice, the normal physiological function of PrP, the causative agent implicated in transmissible spongiform encephalopathies (TSE), remains ..
  97. pmc Efficient transmission of two different sheep scrapie isolates in transgenic mice expressing the ovine PrP gene
    C Crozet
    Unité de Virologie ATNC, Agence Francaise de Securite Sanitaire des Aliments, Lyon, France
    J Virol 75:5328-34. 2001
    ..of the incubation periods, some of the mice inoculated with this isolate showed low or undetectable levels of PrPsc, as detected by both Western blotting and immunohistochemistry...
  98. ncbi Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies
    F L Heppner
    Institute of Neuropathology, Institute of Laboratory Animal Science, Institute of Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, CH 8091 Zurich, Switzerland
    Science 294:178-82. 2001
    ..To circumvent this, we expressed an anti-prion protein (anti-PrP) mu chain in Prnp(o/o) mice...
  99. pmc Changing a single amino acid in the N-terminus of murine PrP alters TSE incubation time across three species barriers
    R M Barron
    Institute for Animal Health, Neuropathogenesis Unit, Edinburgh, UK
    EMBO J 20:5070-8. 2001
    The PrP gene of the host exerts a major influence over the outcome of transmissible spongiform encephalopathy (TSE) disease, but the mechanism by which this is achieved is not understood...
  100. ncbi PrPC directly interacts with proteins involved in signaling pathways
    C Spielhaupter
    Max von Pettenkofer Institute, Department of Virology, Gene Center Munich, Ludwig Maximilians University of Munich, Feodor Lynen Strasse 25, D 81377 Munich, Germany
    J Biol Chem 276:44604-12. 2001
    The cellular prion protein (PrP(C)) is a conserved glycoprotein predominantly expressed in neuronal cells. Its purpose in living cells is still enigmatic...
  101. ncbi Endocytic intermediates involved with the intracellular trafficking of a fluorescent cellular prion protein
    Ana C Magalhaes
    Laboratorio de Neurofarmacologia, Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270 910, Brazil
    J Biol Chem 277:33311-8. 2002
    We have investigated the intracellular traffic of PrP(c), a glycosylphosphatidylinositol (GPI)-anchored protein implicated in spongiform encephalopathies...

Research Grants4

  1. Reconstitution of Prion Transmission in Cells
    Ilia Baskakov; Fiscal Year: 2003
    ..The ultimate direct proof of the "protein only hypothesis', the reconstitution of prpSc in vitro from noninfectious PrP, has not been achieved yet...
  2. Reconstitution of Prion Infectivity
    Ilia Baskakov; Fiscal Year: 2005
    ..The "protein only hypothesis" postulates that an abnormal isoform of PrP (PrPSc) acts as an infectious agent and propagates its pathological conformation using normal isoform (PrPC) as a ..
  3. Experimental Creutzfeldt Jacob Disease
    Laura Manuelidis; Fiscal Year: 2007
    ..with host molecules to provoke pathological changes, and we think this is the origin of host prion protein (PrP) amyloid...
  4. Therapeutic Monoclonal Antibodies for Human Prion Diseases
    MARTIN JOSEPH SADOWSKI; Fiscal Year: 2010
    ..with a conformational transformation of cellular prion protein PrPC into a toxic, infectious, and self-replicating PrPSC conformer for which no effective treatment is currently available...