prion protein

Summary

Gene Symbol: prion protein
Description: prion protein
Alias: ASCR, AltPrP, CD230, CJD, GSS, KURU, PRIP, PrP, PrP27-30, PrP33-35C, PrPc, p27-30, CD230 antigen, prion-related protein
Species: human

Top Publications

  1. ncbi First experimental transmission of fatal familial insomnia
    J Tateishi
    Department of Neuropathology, Kyushu University, Fukuoka, Japan
    Nature 376:434-5. 1995
  2. pmc Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene
    L G Goldfarb
    Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 88:10926-30. 1991
  3. ncbi Polymorphisms of the prion protein gene (PRNP) in a Korean population
    Byung Hoon Jeong
    Ilsong Institute of Life Science, Hallym University, Ilsong Building, 1605 4, Gwanyang dong, Dongan Gu, 431 060, Anyang, Kyounggi Do, South Korea
    J Hum Genet 49:319-24. 2004
  4. pmc Diverse effects on the native β-sheet of the human prion protein due to disease-associated mutations
    Wei Chen
    Department of Bioengineering, University of Washington, Seattle, Washington 98195 5013, United States
    Biochemistry 49:9874-81. 2010
  5. pmc Prion protein interacts with BACE1 protein and differentially regulates its activity toward wild type and Swedish mutant amyloid precursor protein
    Heledd H Griffiths
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 286:33489-500. 2011
  6. pmc Interaction between human prion protein and amyloid-beta (Abeta) oligomers: role OF N-terminal residues
    Shugui Chen
    Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 285:26377-83. 2010
  7. ncbi Signal transduction through prion protein
    S Mouillet-Richard
    Différenciation Cellulaire, CNRS Institut Pasteur, 75724 Paris Cedex 15, France
    Science 289:1925-8. 2000
  8. pmc NMR solution structure of the human prion protein
    R Zahn
    Institut fur Molekularbiologie und Biophysik, Eidgenossische Technische Hochschule Honggerberg, CH 8093 Zurich, Switzerland
    Proc Natl Acad Sci U S A 97:145-50. 2000
  9. ncbi Genetic prion disease: the EUROCJD experience
    Gabor G Kovacs
    Austrian Reference Centre for Human Prion Diseases OERPE, Vienna, Austria
    Hum Genet 118:166-74. 2005
  10. ncbi Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease
    M S Palmer
    Department of Biochemistry and Molecular Genetics, St Mary s Hospital Medical School, London, UK
    Nature 352:340-2. 1991

Detail Information

Publications334 found, 100 shown here

  1. ncbi First experimental transmission of fatal familial insomnia
    J Tateishi
    Department of Neuropathology, Kyushu University, Fukuoka, Japan
    Nature 376:434-5. 1995
    ..Here we report the successful transmission of the disease to experimental animals, placing FFI within the group of infectious cerebral amyloidoses...
  2. pmc Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene
    L G Goldfarb
    Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 88:10926-30. 1991
    The PRNP gene, encoding the amyloid precursor protein that is centrally involved in Creutzfeldt-Jakob disease (CJD), has an unstable region of five variant tandem octapeptide coding repeats between codons 51 and 91...
  3. ncbi Polymorphisms of the prion protein gene (PRNP) in a Korean population
    Byung Hoon Jeong
    Ilsong Institute of Life Science, Hallym University, Ilsong Building, 1605 4, Gwanyang dong, Dongan Gu, 431 060, Anyang, Kyounggi Do, South Korea
    J Hum Genet 49:319-24. 2004
    Human prion protein gene (PRNP) has been considered to be involved in the susceptibility of humans to prion diseases...
  4. pmc Diverse effects on the native β-sheet of the human prion protein due to disease-associated mutations
    Wei Chen
    Department of Bioengineering, University of Washington, Seattle, Washington 98195 5013, United States
    Biochemistry 49:9874-81. 2010
    ..diseases are fatal neurodegenerative disorders that involve the conversion of the normal cellular form of the prion protein (PrP(C)) to a misfolded pathogenic form (PrP(Sc))...
  5. pmc Prion protein interacts with BACE1 protein and differentially regulates its activity toward wild type and Swedish mutant amyloid precursor protein
    Heledd H Griffiths
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 286:33489-500. 2011
    ..We have reported previously that the cellular prion protein (PrP(C)) inhibited the action of BACE1 toward human wild type APP (APP(WT)) in cellular models and that the ..
  6. pmc Interaction between human prion protein and amyloid-beta (Abeta) oligomers: role OF N-terminal residues
    Shugui Chen
    Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 285:26377-83. 2010
    ..that at least some of the neurotoxic effects of these oligomers may be mediated by specific binding to the prion protein, PrP(C), on the cell surface (Laurén, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., and Strittmatter, S...
  7. ncbi Signal transduction through prion protein
    S Mouillet-Richard
    Différenciation Cellulaire, CNRS Institut Pasteur, 75724 Paris Cedex 15, France
    Science 289:1925-8. 2000
    The cellular prion protein PrPc is a glycosylphosphatidylinositol-anchored cell-surface protein whose biological function is unclear...
  8. pmc NMR solution structure of the human prion protein
    R Zahn
    Institut fur Molekularbiologie und Biophysik, Eidgenossische Technische Hochschule Honggerberg, CH 8093 Zurich, Switzerland
    Proc Natl Acad Sci U S A 97:145-50. 2000
    The NMR structures of the recombinant human prion protein, hPrP(23-230), and two C-terminal fragments, hPrP(90-230) and hPrP(121-230), include a globular domain extending from residues 125-228, for which a detailed structure was obtained,..
  9. ncbi Genetic prion disease: the EUROCJD experience
    Gabor G Kovacs
    Austrian Reference Centre for Human Prion Diseases OERPE, Vienna, Austria
    Hum Genet 118:166-74. 2005
    ..spongiform encephalopathies (TSEs) or prion diseases are characterised by disease-specific mutations in the prion protein gene (PRNP)...
  10. ncbi Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease
    M S Palmer
    Department of Biochemistry and Molecular Genetics, St Mary s Hospital Medical School, London, UK
    Nature 352:340-2. 1991
    ..Despite their experimental transmissibility, missense and insertional mutations in the prion protein gene are associated with both GSS and familial CJD, demonstrating that the human familial cases are autosomal ..
  11. pmc Oxidation of Helix-3 methionines precedes the formation of PK resistant PrP
    Tamar Canello
    Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, and Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel
    PLoS Pathog 6:e1000977. 2010
    ..at both Met residues 206 and 213 destabilize the alpha-fold, suggesting oxidation may facilitate the conversion of PrPC into PrPSc...
  12. pmc Molecular conformation and dynamics of the Y145Stop variant of human prion protein in amyloid fibrils
    Jonathan J Helmus
    Department of Chemistry, Ohio State University, Columbus, OH 43210, USA
    Proc Natl Acad Sci U S A 105:6284-9. 2008
    A C-terminally truncated Y145Stop variant of the human prion protein (huPrP23-144) is associated with a hereditary amyloid disease known as PrP cerebral amyloid angiopathy...
  13. ncbi Mutations in familial Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker's syndrome
    D Goldgaber
    Department of Psychiatry, State University of New York, Stony Brook 11794 8101
    Exp Neurol 106:204-6. 1989
    ..spongiform encephalopathies: Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker's syndrome (GSS), and kuru in man, and scrapie in animals...
  14. 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...
  15. ncbi Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene
    R Medori
    Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106
    N Engl J Med 326:444-9. 1992
    ..Five other family members who died of this disease, which we termed "fatal familial insomnia," had broader neuropathologic changes suggesting that fatal familial insomnia could be a prion disease...
  16. doi Green tea extracts interfere with the stress-protective activity of PrP and the formation of PrP
    Angelika S Rambold
    Department of Biochemistry, Neurobiochemistry, Ludwig Maximilians Universitat Munchen, Munchen, Germany
    J Neurochem 107:218-29. 2008
    A hallmark in prion diseases is the conformational transition of the cellular prion protein (PrP(C)) into a pathogenic conformation, designated scrapie prion protein (PrP(Sc)), which is the essential constituent of infectious prions...
  17. ncbi Identification of novel proteinase K-resistant C-terminal fragments of PrP in Creutzfeldt-Jakob disease
    Wen Quan Zou
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 278:40429-36. 2003
    ..disorders including Creutzfeldt-Jakob disease (CJD) in humans, is the conversion of the normal or cellular prion protein (PrPC) into the abnormal or scrapie isoform (PrPSc)...
  18. ncbi A new point mutation of the prion protein gene in Creutzfeldt-Jakob disease
    M Pocchiari
    Laboratory of Virology, Istituto Superiore di Sanita, Rome, Italy
    Ann Neurol 34:802-7. 1993
    Complete sequencing of the prion protein open reading frame of a 68-year-old woman affected by a familial form of Creutzfeldt-Jakob disease (CJD) revealed a new mutation at codon 210 resulting in the substitution of isoleucine for valine...
  19. pmc Amyloid-β induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease
    Ji Won Um
    Cellular Neuroscience, Neurodegeneration and Repair Program, Department of Neurology, Yale University School of Medicine, New Haven, CT, USA
    Prion 7:37-41. 2013
    ..Amyloid-β (Aβ) oligomers are potent synaptotoxins thought to mediate AD-related phenotypes. Cellular prion protein (PrP(C)) has been identified as a high-affinity receptor for Aβ oligomers...
  20. doi Total prion protein levels in the cerebrospinal fluid are reduced in patients with various neurological disorders
    Felix Meyne
    National TSE Reference Center at Department of Neurology, Georg August University, Gottingen, Germany
    J Alzheimers Dis 17:863-73. 2009
    We performed a study on levels of the total prion protein (PrP) in humans affected by different neurological diseases and assessed the influence of several factors such as age, gender, and disease severity on the cerebrospinal fluid PrP ..
  21. ncbi Identification of three novel mutations (E196K, V203I, E211Q) in the prion protein gene (PRNP) in inherited prion diseases with Creutzfeldt-Jakob disease phenotype
    K Peoc'h
    Centre de Recherche C Bernard, IFR 6, Service de Biochimie et Biologie Moléculaire Pr J M Launay, Hopital Lariboisiere, Paris, France
    Hum Mutat 15:482. 2000
    Inherited prion diseases are characterized by mutations in the PRNP gene encoding the prion protein (PrP)...
  22. ncbi Molecular modulation of expression of prion protein by heat shock
    Woei Cherng Shyu
    Department of Neurology, Mackay Memorial Hospital, Taipei, Taiwan, ROC
    Mol Neurobiol 26:1-12. 2002
    ..spongiform encephalopathies) are associated with the conversion of the normal cellular form of the prion protein (PrPC) to an abnormal scrapie-isoform (PrP(Sc)...
  23. pmc Cellular prion protein expression is not regulated by the Alzheimer's amyloid precursor protein intracellular domain
    Victoria Lewis
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
    PLoS ONE 7:e31754. 2012
    ..The cellular prion protein, PrP(C), modulates the post-translational processing of the AD amyloid precursor protein (APP), through its ..
  24. pmc Familial CJD associated PrP mutants within transmembrane region induced Ctm-PrP retention in ER and triggered apoptosis by ER stress in SH-SY5Y cells
    Xin Wang
    State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People s Republic of China
    PLoS ONE 6:e14602. 2011
    Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP) gene that are presumed to favor conversion of the cellular isoform of PrP (PrP(C)) to the pathogenic one (PrP(Sc))...
  25. doi Prion-like aggregates: infectious agents in human disease
    Gunilla T Westermark
    Department of Medical Cell Biology and Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
    Trends Mol Med 16:501-7. 2010
    ..The misfolding and aggregation of the prion protein are akin to the genesis of amyloid fibrils formed by several human and animal proteins associated with more ..
  26. doi Human prion protein mutants with deleted and inserted octarepeats undergo different pathways to trigger cell apoptosis
    Kun Xu
    Department of Microbiology, School of Medicine, Xi an Jiao Tong University, Xi an, 710061, People s Republic of China
    J Mol Neurosci 43:225-34. 2011
    Octarepeats region sequence is one of the most important characteristics of PrP topology...
  27. doi PRNP allelic series from 19 years of prion protein gene sequencing at the MRC Prion Unit
    Jon A Beck
    MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK
    Hum Mutat 31:E1551-63. 2010
    Mutation of the human prion protein gene (PRNP) open reading frame (ORF) accounts for almost all reported familial concurrence of prion disease...
  28. doi Alzheimer's disease brain-derived amyloid-β-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein
    Andrew E Barry
    Department of Pharmacology and Therapeutics and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland
    J Neurosci 31:7259-63. 2011
    Synthetic amyloid-β protein (Aβ) oligomers bind with high affinity to cellular prion protein (PrP(C)), but the role of this interaction in mediating the disruption of synaptic plasticity by such soluble Aβ in vitro is controversial...
  29. pmc Assessment of Alzheimer's disease case-control associations using family-based methods
    Brit Maren M Schjeide
    MassGeneral Institute for Neurodegenerative Disease MIND, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Neurogenetics 10:19-25. 2009
    ..Further fine-mapping and functional analyses are warranted to elucidate the potential biochemical mechanisms and epidemiological relevance of these genes...
  30. pmc Pathogenic mutations in the hydrophobic core of the human prion protein can promote structural instability and misfolding
    Marc W van der Kamp
    Department of Bioengineering, University of Washington, Seattle, WA 98195 5013, USA
    J Mol Biol 404:732-48. 2010
    Transmissible spongiform encephalopathies, or prion diseases, are caused by misfolding and aggregation of the prion protein PrP...
  31. pmc Co-existence of scrapie prion protein types 1 and 2 in sporadic Creutzfeldt-Jakob disease: its effect on the phenotype and prion-type characteristics
    Ignazio Cali
    Department of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Brain 132:2643-58. 2009
    ..Creutzfeldt-Jakob disease (sCJD), based on the methionine/valine polymorphic genotype of codon 129 of the prion protein (PrP) gene and the presence of either one of the two protease K-resistant scrapie prion protein (PrP(Sc)) ..
  32. ncbi Prion diseases of humans and animals: their causes and molecular basis
    J Collinge
    MRC Prion Unit and Department of Neurogenetics, Imperial College School of Medicine at St Mary s, London, United Kingdom
    Annu Rev Neurosci 24:519-50. 2001
    ..Prions appear to be composed principally or entirely of abnormal isoforms of a host-encoded glycoprotein, prion protein. Prion propagation involves recruitment of host cellular prion protein, composed primarily of alpha-helical ..
  33. pmc Methionine sulfoxides on prion protein Helix-3 switch on the alpha-fold destabilization required for conversion
    Giorgio Colombo
    Isto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, Milano, Italy
    PLoS ONE 4:e4296. 2009
    The conversion of the cellular prion protein (PrP(C)) into the infectious form (PrP(Sc)) is the key event in prion induced neurodegenerations...
  34. ncbi The expression and potential function of cellular prion protein in human lymphocytes
    R Li
    Institute of Pathology, Division of Neuropathology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106 4943, USA
    Cell Immunol 207:49-58. 2001
    We examined expression of the normal cellular prion protein (PrP(C)) in human peripheral blood mononuclear cells (PBMC) and in transfected neuroblastoma cells with a panel of six monoclonal antibodies (Mabs)...
  35. doi Human prion protein (PrP) 219K is converted to PrPSc but shows heterozygous inhibition in variant Creutzfeldt-Jakob disease infection
    Masaki Hizume
    Division of CJD Science and Technology, Tohoku University Graduate School of Medicine, Sendai 980 8575, Japan
    J Biol Chem 284:3603-9. 2009
    b>Prion protein gene (PRNP) E219K is a human polymorphism commonly occurring in Asian populations but is rarely found in patients with sporadic Creutzfeldt-Jakob disease (CJD)...
  36. ncbi Molecular genetics of human prion diseases in Germany
    O Windl
    Institut für Neuropathologie, Universitat Gottingen, Germany
    Hum Genet 105:244-52. 1999
    ..Mutations and polymorphisms in the sequence of the coding region of the prion protein gene (PRNP) have been established as an important factor in all of these three types of prion diseases...
  37. doi Cytosolic PrP induces apoptosis of cell by disrupting microtubule assembly
    Xiao Li Li
    State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Ying Xin Rd 100, Beijing, 100052, People s Republic of China
    J Mol Neurosci 43:316-25. 2011
    b>Prion protein (PrP) is able to bind with tubulin and to interfere with the formation of microtubule. To investigate the influence of accumulation of cytosolic PrP in cytoplasm on microtubule, plasmid pcDNA3...
  38. ncbi Prion proteins with insertion mutations have altered N-terminal conformation and increased ligand binding activity and are more susceptible to oxidative attack
    Shaoman Yin
    Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44120, USA
    J Biol Chem 281:10698-705. 2006
    We compared the biochemical properties of a wild type recombinant normal human cellular prion protein, rPrP(c), with a recombinant mutant human prion protein that has three additional octapeptide repeats, rPrP(8OR)...
  39. pmc Molecular architecture of human prion protein amyloid: a parallel, in-register beta-structure
    Nathan J Cobb
    Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 104:18946-51. 2007
    ..diseases that are associated with conformational conversion of the normally monomeric and alpha-helical prion protein, PrP(C), to the beta-sheet-rich PrP(Sc)...
  40. ncbi Regulatory sequences of the PRNP gene influence susceptibility to sporadic Creutzfeldt-Jakob disease
    Jolanta Bratosiewicz-Wasik
    Department of Virology, Medical University of Silesia, 41 200 Sosnowiec, Narcyzow 1, Poland, and Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Canada
    Neurosci Lett 411:163-7. 2007
    The prion diseases are fatal neurodegenerative disorders that afflict both humans and animals. They comprise kuru, Creutzfeldt-Jakob disease (CJD), Gerstmman-Straussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI)...
  41. 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
    ..PS1 and PS2) and amyloid precursor protein (APP) are associated with FAD, whereas mutations in the prion protein (PrP) gene are associated with prion disease...
  42. doi PRNP 1368 polymorphism is not associated with sporadic Creutzfeldt-Jakob disease in the Korean population
    B H Jeong
    Ilsong Institute of Life Science, Hallym University, Dongan Gu, Anyang, Kyounggi Do, South Korea
    Eur J Neurol 15:846-50. 2008
    Human prion protein gene (PRNP) is considered a critical and fundamental gene in determining the incidence of human prion diseases...
  43. pmc Function of PrPC (1-OPRD) in biological activities of gastric cancer cell lines
    Jie Liang
    State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi an, China
    J Cell Mol Med 13:4453-64. 2009
    ..disease is inherited and one of the important genetic mutations occurs in the octapeptide repeat region of prion protein gene...
  44. ncbi Silencing of prion protein sensitizes breast adriamycin-resistant carcinoma cells to TRAIL-mediated cell death
    Franck Meslin
    INSERM U753, Laboratoire d Immunologie des Tumeurs Humaines, Interaction Effecteurs Cytotoxiques Système Tumoral, Institut Gustave Roussy PR1 and IFR 54, Villejuif, France
    Cancer Res 67:10910-9. 2007
    ..to the proapoptotic action of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and cellular prion protein (PrPc) function, using the TRAIL-sensitive MCF-7 human breast adenocarcinoma cell line and two TRAIL-resistant ..
  45. ncbi Polymorphisms in the prion protein gene and in the doppel gene increase susceptibility for Creutzfeldt-Jakob disease
    Esther A Croes
    Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam, The Netherlands
    Eur J Hum Genet 12:389-94. 2004
    The prion protein gene (PRNP) plays a central role in the origin of Creutzfeldt-Jakob disease (CJD), but there is growing interest in other polymorphisms that may be involved in CJD...
  46. ncbi Association of sporadic Creutzfeldt-Jakob disease with homozygous genotypes at PRNP codons 129 and 219 in the Korean population
    Byung Hoon Jeong
    Ilsong Institute of Life Science, Hallym University, Ilsong Building, 1605 4 Gwanyang dong, Dongan Gu, Anyang, Kyonggi do 431 060, South Korea
    Neurogenetics 6:229-32. 2005
    Human prion protein gene (PRNP) is considered an important gene in determining the incidence of human transmissible spongiform encephalopathies or prion diseases...
  47. pmc Molecular origin of Gerstmann-Sträussler-Scheinker syndrome: insight from computer simulation of an amyloidogenic prion peptide
    Isabella Daidone
    Department of Chemistry, Chemical Engineering and Materials, University of L Aquila, L Aquila, Italy
    Biophys J 100:3000-7. 2011
    ..Here, we characterize the folding of a peptide consisting of residues 109-122 of the Syrian hamster prion protein (the H1 peptide) and of a more amyloidogenic A117V point mutant that leads in humans to an inheritable form of ..
  48. pmc Intermolecular alignment in Y145Stop human prion protein amyloid fibrils probed by solid-state NMR spectroscopy
    Jonathan J Helmus
    Department of Chemistry, The Ohio State University, Columbus, 43210, United States
    J Am Chem Soc 133:13934-7. 2011
    The Y145Stop mutant of human prion protein, huPrP23-144, has been linked to PrP cerebral amyloid angiopathy, an inherited amyloid disease, and also serves as a valuable in vitro model for investigating the molecular basis of amyloid ..
  49. doi Prion protein expression and the M129V polymorphism of the PRNP gene in patients with colorectal cancer
    Anna G Antonacopoulou
    Clinical Oncology Laboratory, Medical School, University of Patras, Rion, Greece
    Mol Carcinog 49:693-9. 2010
    The prion protein, PrP(C), is known mostly for its involvement in neurodegenerative spongiform encephalopathies...
  50. pmc Unaltered prion protein expression in Alzheimer disease patients
    Eri Saijo
    Department of Microbiology, Immunology and Molecular Genetic, University of Kentucky Medical Center, Lexington, KY, USA
    Prion 5:109-16. 2011
    The suggested role of cellular prion protein (PrP (C) ) in mediating the toxic effects of oligomeric amyloid β peptide (Aβ) in Alzheimer disease (AD) is controversial...
  51. doi Gerstmann-Sträussler-Scheinker disease
    Paweł P Liberski
    Department of Molecular Pathology and Neuropathology, Medical University Lodz, Lodz, Poland
    Adv Exp Med Biol 724:128-37. 2012
    ..and the first human transmissible spongiform encephalopathy (TSE) in which a mutation in a gene encoding for prion protein (PrP) was discovered...
  52. pmc A polymorphism in the regulatory region of PRNP is associated with increased risk of sporadic Creutzfeldt-Jakob disease
    Pascual Sanchez-Juan
    Neurology Department, University Hospital Marqués de Valdecilla and CIBERNED, Santander, Spain
    BMC Med Genet 12:73. 2011
    ..An important determinant for CJD risk and phenotype is the M129V polymorphism of the human prion protein gene (PRNP), but there are also other coding and non-coding polymorphisms inside this gene.
  53. pmc Identification of adjacent binding sites for the YY1 and E4BP4 transcription factors in the ovine PrP (Prion) gene promoter
    Stewart T G Burgess
    Roslin Institute and R D SVS, Neuropathogenesis Division, University of Edinburgh, Roslin, Midlothian EH25 9PS, United Kingdom
    J Biol Chem 284:6716-24. 2009
    The PrP gene encodes the cellular isoform of the prion protein (PrP(c)) which has been shown to be crucial to the development of transmissible spongiform encephalopathies (TSEs)...
  54. ncbi Truncated forms of the human prion protein in normal brain and in prion diseases
    S G Chen
    Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 270:19173-80. 1995
    The cellular form of the prion protein (PrPc) is a glycoprotein anchored to the cell membrane by a glycosylphosphatidylinositol moiety...
  55. pmc Structural polymorphism in amyloids: new insights from studies with Y145Stop prion protein fibrils
    Eric M Jones
    Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 286:42777-84. 2011
    The C-terminally-truncated human prion protein variant Y145Stop (or PrP23-144), associated with a familial prion disease, provides a valuable model for studying the fundamental properties of protein amyloids...
  56. ncbi The prion protein has RNA binding and chaperoning properties characteristic of nucleocapsid protein NCP7 of HIV-1
    C Gabus
    LaboRetro, Unité de Virologie Humaine INSERM Ecole Normale Superieure de Lyon ENS 412, ENS de Lyon, 46 allee d Italie, Lyon 69364, France
    J Biol Chem 276:19301-9. 2001
    ..are fatal neurodegenerative diseases associated with the accumulation of a protease-resistant form of the prion protein (PrP). Although PrP is conserved in vertebrates, its function remains to be identified...
  57. doi Hypoxia-inducible factor-1 α regulates prion protein expression to protect against neuron cell damage
    Jae Kyo Jeong
    Center for Healthcare Technology Development, Korea Zoonoses Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk, South Korea
    Neurobiol Aging 33:1006.e1-10. 2012
    The human prion protein fragment, PrP (106-126), may contain a majority of the pathological features associated with the infectious scrapie isoform of PrP, known as PrP(Sc)...
  58. doi No evidence for prion protein gene locus multiplication in Creutzfeldt-Jakob disease
    Steven J Collins
    Australian National CJD Registry, Department of Pathology, The University of Melbourne, Parkville 3010, Australia
    Neurosci Lett 472:16-8. 2010
    ..of a similar disorder occurs in around 50-90% of patients harboring the most common, disease-associated, prion protein gene (PRNP) mutations...
  59. doi Prion protein expression alters APP cleavage without interaction with BACE-1
    Patrick C McHugh
    Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
    Neurochem Int 61:672-80. 2012
    The prion protein (PrP) and the beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE-1) are both copper binding proteins, but are associated with two separate neurodegenerative diseases...
  60. pmc Mutant prion protein expression is associated with an alteration of the Rab GDP dissociation inhibitor alpha (GDI)/Rab11 pathway
    Tania Massignan
    Dulbecco Telethon Institute DTI c o Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
    Mol Cell Proteomics 9:611-22. 2010
    The prion protein (PrP) is a glycosylphosphatidylinositol-anchored membrane glycoprotein that plays a vital role in prion diseases, a class of fatal neurodegenerative disorders of humans and animals...
  61. pmc Co-occurrence of types 1 and 2 PrP(res) in sporadic Creutzfeldt-Jakob disease MM1
    Atsushi Kobayashi
    Division of Neurological Science, Center for Prion Research, Tohoku University Graduate School of Medicine, Sendai, Japan
    Am J Pathol 178:1309-15. 2011
    The genotype (M/M, M/V, or V/V) at polymorphic codon 129 of the human prion protein (PrP) gene and the type (1 or 2) of protease-resistant PrP (PrP(res)) in the brain are major determinants of the clinicopathological phenotypes of ..
  62. ncbi A prion-linked psychiatric disorder
    H B Samaia
    Nature 390:241. 1997
  63. ncbi Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene
    P Brown
    Laboratory of CNS Studies, NINDS, NIH, Bethesda, MD 20892
    Neurology 42:422-7. 1992
    ..family of English origin with an unusually early onset and long-duration form of Creutzfeldt-Jakob disease (CJD) had a heterozygous insert mutation in the region of repeating octapeptide coding sequences between codons 51 and ..
  64. pmc Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP
    Casper Jansen
    Dutch Surveillance Centre for Prion Diseases, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands
    Acta Neuropathol 119:189-97. 2010
    Stop codon mutations in the gene encoding the prion protein (PRNP) are very rare and have thus far only been described in two patients with prion protein cerebral amyloid angiopathy (PrP-CAA)...
  65. pmc Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties
    Matthew T Bishop
    National Creutzfeldt Jakob Disease Surveillance Unit, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom
    Proc Natl Acad Sci U S A 107:12005-10. 2010
    ..To categorize sCJD cases, the prion protein (PrP) codon 129 genotype and the biochemical characteristics of the disease-associated form of PrP (PrP(Sc)) ..
  66. pmc Retrotranslocation of prion proteins from the endoplasmic reticulum by preventing GPI signal transamidation
    Aarthi Ashok
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 19:3463-76. 2008
    Neurodegeneration in diseases caused by altered metabolism of mammalian prion protein (PrP) can be averted by reducing PrP expression...
  67. pmc PRNP variation in UK sporadic and variant Creutzfeldt Jakob disease highlights genetic risk factors and a novel non-synonymous polymorphism
    Matthew T Bishop
    National CJD Surveillance Unit, University of Edinburgh, Bryan Matthews Building, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK
    BMC Med Genet 10:146. 2009
    Genetic analysis of the human prion protein gene (PRNP) in suspect cases of Creutzfeldt-Jakob disease (CJD) is necessary for accurate diagnosis and case classification...
  68. pmc Design of anti- and pro-aggregation variants to assess the effects of methionine oxidation in human prion protein
    Christina Wolschner
    Max Planck Institut fur Biochemie, Am Klopferspitz 18, D 82152 Martinsried, Germany
    Proc Natl Acad Sci U S A 106:7756-61. 2009
    Prion disease is characterized by the alpha-->beta structural conversion of the cellular prion protein (PrP(C)) into the misfolded and aggregated "scrapie" (PrP(Sc)) isoform...
  69. pmc Beta-sheet core of human prion protein amyloid fibrils as determined by hydrogen/deuterium exchange
    Xiaojun Lu
    Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 104:1510-5. 2007
    Propagation of transmissible spongiform encephalopathies is associated with the conversion of normal prion protein, PrP(C), into a misfolded, oligomeric form, PrP(Sc)...
  70. doi D178N, 129Val and N171S, 129Val genotype in a family with Creutzfeldt-Jakob disease
    Brian S Appleby
    Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Dement Geriatr Cogn Disord 30:424-31. 2010
    ..disease (CJD(D178N,)(129V)) are two phenotypes that share a common point mutation at codon 178 of the prion protein gene (PRNP), but differ in their polymorphism at codon 129 of the mutant allele...
  71. ncbi Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS
    Jie Liang
    State Key Laboratory of Cancer Biology, Xijing Hospital, Fourth Military Medical University, 15 West Chang Le Rd, Xi an, Shaanxi Province, China
    FASEB J 21:2247-56. 2007
    The function of cellular prion protein (PrP(C)), the essential protein for the pathogenesis and transmission of prion diseases, is still largely unknown...
  72. pmc Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains
    M Vey
    Department of Neurology, University of California, San Francisco 94143, USA
    Proc Natl Acad Sci U S A 93:14945-9. 1996
    Results of transgenetic studies argue that the scrapie isoform of the prion protein (PrPSc) interacts with the substrate cellular PrP (PrPC) during conversion into nascent PrPSc...
  73. ncbi Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome
    K Hsiao
    Department of Neurology, University of California, San Francisco
    Nature 338:342-5. 1989
    ..Protease-resistant prion protein (PrP) and PrP-immunoreactive amyloid plaques with characteristic morphology accumulate in the brains of these ..
  74. ncbi Identification of distinct N-terminal truncated forms of prion protein in different Creutzfeldt-Jakob disease subtypes
    Gianluigi Zanusso
    Department of Neurological and Visual Sciences, Section of Neurology and Agricultural and Industrial Biotechnologies, University of Verona, 37134 Verona, Italy
    J Biol Chem 279:38936-42. 2004
    In prion diseases, the cellular prion protein (PrP(C)) is converted to an insoluble and protease-resistant abnormal isoform termed PrP(Sc)...
  75. 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...
  76. doi Clinical features of rapidly progressive Alzheimer's disease
    Christian Schmidt
    Department of Neurology, Hospital of the Georg August University Goettingen, Goettingen, Germany
    Dement Geriatr Cogn Disord 29:371-8. 2010
    ..To characterize clinical features, CSF biomarkers and genetic polymorphisms of patients suffering from a rapidly progressing subtype of Alzheimer's dementia (rpAD)...
  77. pmc Functional depletion of mahogunin by cytosolically exposed prion protein contributes to neurodegeneration
    Oishee Chakrabarti
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA
    Cell 137:1136-47. 2009
    The pathways leading from aberrant Prion protein (PrP) metabolism to neurodegeneration are poorly understood. Some familial PrP mutants generate increased (Ctm)PrP, a transmembrane isoform associated with disease...
  78. pmc Octapeptide repeat insertions in the prion protein gene and early onset dementia
    E A Croes
    Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam, The Netherlands
    J Neurol Neurosurg Psychiatry 75:1166-70. 2004
    ..common familial early onset dementia mutations are found in the genes involved in Alzheimer's disease; the amyloid precursor protein (APP) and the presenilin 1 and 2 (PSEN1 and 2) genes; the prion protein gene (PRNP) may be involved.
  79. ncbi Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics
    Simon Mead
    Medical Research Council Prion Unit, and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK
    Science 300:640-3. 2003
    ..Heterozygosity for a common polymorphism in the human prion protein gene (PRNP) confers relative resistance to prion diseases...
  80. ncbi Cellular prion protein is expressed on endothelial cells and is released during apoptosis on membrane microparticles found in human plasma
    Jan Simak
    Laboratory of Cellular Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 28092, USA
    Transfusion 42:334-42. 2002
    ..A conformational isoform of prion protein (PrPsc) is believed to be the TSE-infectious agent that propagates by converting the cellular prion protein (..
  81. ncbi Influence of the prion protein and the apolipoprotein E genotype on the Creutzfeldt-Jakob Disease phenotype
    B Van Everbroeck
    Laboratory of Neurobiology, Born Bunge Foundation, University of Antwerp, Universiteitsplein 1, B 2610 Antwerp, Belgium
    Neurosci Lett 313:69-72. 2001
    We investigated the risk associated with the codon 129 polymorphism in the prion protein gene (PRNP) and apolipoprotein E gene (APOE) isoforms for development of Creutzfeldt-Jakob disease (CJD) (n=126) and the possible influences on the ..
  82. ncbi Cytosolic prion protein is not toxic and protects against Bax-mediated cell death in human primary neurons
    Xavier Roucou
    Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital
    J Biol Chem 278:40877-81. 2003
    ..and Lindquist, S. (2002) Science 298, 1781-1785). In this study, we investigated whether accumulation of prion protein (PrP) in the cytosol is toxic to human neurons in primary culture...
  83. doi Heat shock protein 104 inhibited the fibrillization of prion peptide 106-126 and disassembled prion peptide 106-126 fibrils in vitro
    Ying hui Liu
    State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Ying Xin Rd 100, Beijing 100052, People s Republic of China
    Int J Biochem Cell Biol 43:768-74. 2011
    ..Prion peptide of aa 106-126 (PrP106-126) exhibits many PrP(Sc)-like biochemical features, forming amyloid-like fibrils in vitro...
  84. pmc Ligand binding promotes prion protein aggregation--role of the octapeptide repeats
    Shuiliang Yu
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106 7288, USA
    FEBS J 275:5564-75. 2008
    Aggregation of the normal cellular prion protein, PrP, is important in the pathogenesis of prion disease. PrP binds glycosaminoglycan (GAG) and divalent cations, such as Cu(2+) and Zn(2+)...
  85. doi Regulation of prion gene expression by transcription factors SP1 and metal transcription factor-1
    Shayne A Bellingham
    Department of Biochemistry and Molecular Biology, The University of Melbourne, Victoria, Australia
    J Biol Chem 284:1291-301. 2009
    Prion diseases are associated with the conformational conversion of the host-encoded cellular prion protein into an abnormal pathogenic isoform...
  86. ncbi A mutant prion protein displays an aberrant membrane association when expressed in cultured cells
    S Lehmann
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 270:24589-97. 1995
    Inherited forms of prion disease have been linked to mutations in the gene encoding PrP, a neuronal and glial protein that is attached to the plasma membrane by a glycosyl-phosphatidylinositol (GPI) anchor...
  87. pmc Tau, prions and Aβ: the triad of neurodegeneration
    Lilla Reiniger
    Division of Neuropathology, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, WC1N 3BG, London, UK
    Acta Neuropathol 121:5-20. 2011
    ..This includes the novel finding that tau phosphorylation consistently occurs in sporadic CJD, in the absence of amyloid plaques.
  88. pmc Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice
    Walker S Jackson
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Neuron 63:438-50. 2009
    A crucial tenet of the prion hypothesis is that misfolding of the prion protein (PrP) induced by mutations associated with familial prion disease is, in an otherwise normal mammalian brain, sufficient to generate the infectious agent...
  89. pmc Molecular biology and pathology of prion strains in sporadic human prion diseases
    Pierluigi Gambetti
    Department of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH, 44106, USA
    Acta Neuropathol 121:79-90. 2011
    ..to propagate by the mechanism involving self-perpetuating conformational conversion of the normal form of the prion protein, PrP(C), to the misfolded, pathogenic state, PrP(Sc)...
  90. ncbi Prion protein gene M129 allele is a risk factor for Alzheimer's disease
    M Gacia
    Department of Neurodegenerative Disorders, Medical Research Center, Polish Academy of Sciences, Warszawa, Poland
    J Neural Transm 113:1747-51. 2006
    b>Prion protein gene polymorphism M129V represents a known risk factor for Creutzfeldt-Jakob disease. Recently, the meta-analysis revealed that homozygosity at codon 129 is connected with increased risk of Alzheimer's disease (AD)...
  91. doi A novel protective prion protein variant that colocalizes with kuru exposure
    Simon Mead
    Medical Research Council Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, United Kingdom
    N Engl J Med 361:2056-65. 2009
    b>Kuru is a devastating epidemic prion disease that affected a highly restricted geographic area of the Papua New Guinea highlands; at its peak, it predominantly affected adult women and children of both sexes...
  92. doi A novel insertional mutation in the prion protein gene: clinical and bio-molecular findings
    C Mauro
    Department of Neurological Sciences, First Division of Neurology, Second University of Naples, Via Pansini 5, 80131 Naples, Italy
    J Neurol Neurosurg Psychiatry 79:1395-8. 2008
    ..marked bi-parietal cerebral atrophy, was found to carry a novel seven extra-repeat insertional mutation in the prion protein gene (PRNP)...
  93. doi Survival in Alzheimer's disease is shorter in women carrying heterozygosity at codon 129 of the PRNP gene and no APOE epsilon 4 allele
    Claudia Giannattasio
    Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Rome, Italy
    Dement Geriatr Cogn Disord 25:354-8. 2008
    We assessed the role of the APOE genotype and prion protein polymorphism at codon 129 in predicting the clinical duration of 92 neuropathologically confirmed sporadic Alzheimer's disease patients...
  94. doi Codon 129 polymorphism of prion protein gene in sporadic Alzheimer's disease
    A Poleggi
    Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Rome, Italy
    Eur J Neurol 15:173-8. 2008
    Codon 129 polymorphism of the prion protein gene represents a major genetic risk factor for Creutzfeldt-Jakob disease (CJD)...
  95. pmc A New Transgenic Mouse Model of Gerstmann-Straussler-Scheinker Syndrome Caused by the A117V Mutation of PRNP
    Wenbin Yang
    Department of Neurology, University of Chicago, Illinois 60637, USA
    J Neurosci 29:10072-80. 2009
    ..clinically by the development of progressive ataxia and dementia, and histopathologically by the presence of prion protein (PrP) amyloid plaques in the CNS, especially within the cerebellum...
  96. ncbi Presence of a "CAGA box" in the APP gene unique to amyloid plaque-forming species and absent in all APLP-1/2 genes: implications in Alzheimer's disease
    Bryan Maloney
    Departments of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    FASEB J 18:1288-90. 2004
    ....
  97. ncbi Cytosolic prion protein induces apoptosis in human neuronal cell SH-SY5Y via mitochondrial disruption pathway
    Xin Wang
    State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Ying Xin Rd 100, Beijing 100052, China
    BMB Rep 42:444-9. 2009
    ..Reverse-transfected cytosolic prion protein (PrP) and PrP expressed in the cytosol have been shown to be neurotoxic...
  98. ncbi The effect of disease-associated mutations on the folding pathway of human prion protein
    Adrian C Apetri
    Department of Physiology and Biophysics and Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 279:18008-14. 2004
    Propagation of transmissible spongiform encephalopathies is believed to involve the conversion of cellular prion protein, PrP(C), into a misfolded oligomeric form, PrP(Sc)...
  99. pmc Abbreviated incubation times for human prions in mice expressing a chimeric mouse-human prion protein transgene
    Carsten Korth
    Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 100:4784-9. 2003
    Transgenic (Tg) mouse lines that express chimeric mouse-human prion protein (PrP), designated MHu2M, are susceptible to prions from patients with sporadic Creutzfeldt-Jakob disease (sCJD)...
  100. ncbi All-trans retinoic acid down-regulates prion protein expression independently of granulocyte maturation
    C Rybner
    INSERM U 496, Institut Universitaire d Hématologie IUH, Hopital Saint Louis, Paris, France
    Leukemia 16:940-8. 2002
    The cellular prion protein (PrPc) is a sialoglycoprotein involved in the pathogenesis of prion diseases. It has been identified at the plasma membrane of several cell types...

Research Grants68

  1. Characterization of de novo generation of infectious prions
    Joaquin Castilla; Fiscal Year: 2009
    ..appears to be composed uniquely of a protein which is a conformationally-modified version (PrPSc) of a natural prion protein (PrPC)...
  2. Structure and assembly of the fungal prion HET-s
    William N Wan; Fiscal Year: 2013
    ..BSE) in cattle, chronic wasting disease (CWD) in deer and elk, and several forms of Creutzfeldt-Jakob disease (CJD) in humans...
  3. Impact of Microparticles on Oral TSE Infections
    Joel A Pedersen; Fiscal Year: 2012
    ..hallmark characteristics including the accumulation of a disease-specific structurally abnormal form of the prion protein (PrPSc)...
  4. Liposome-siRNA-Peptide Complexes as Therapy to Cure Prion Diseases in Mouse Model
    Mark D Zabel; Fiscal Year: 2013
    ..Accumulation of PrPRES, a proteinase K (PK) resistant form of the normal prion protein, PrPC appears central to the pathogenesis of these diseases...
  5. Characteristics of Prion Entry and Neuroinvasion Following Nasal Cavity Infection
    Anthony E Kincaid; Fiscal Year: 2013
    ..the mechanisms for the relative efficiency of this route of infection by measuring the amount of normal prion protein present in the lymphoid tissue, the density of innervation, and the ability of the lymphoid tissue to convert ..
  6. TRANSMISSIBLE AND GENETIC NEURODENGENERATIVE DISEASES
    STANLEY PRUSINER; Fiscal Year: 1999
    ..Convergence of many lines of experimental evidence asserts that the scrapie isoform of the prion protein (PrP/Sc) is a necessary component of the infectious scrapie prion yet both PrP/Sc and the normal isoform, PrP/..
  7. CNS DEGENERATION CAUSED BY NOVEL PATHOGENS
    STANLEY PRUSINER; Fiscal Year: 1993
    ..Infectious prion particles are composed largely, if not entirely, of an abnormal isoform of the prion protein (PrP) which is encoded by a chromosomal gene...
  8. Molecular Mechanisms of Prion and Amyloid Propagation
    Christopher P Jaroniec; Fiscal Year: 2013
    ..prions propagate by a mechanism involving the conformational conversion of a largely a-helical cellular prion protein, PrPC, to misfolded, [unreadable]-rich amyloid-like aggregates, PrPSc...
  9. Development of a Biochemical Diagnosis for Creutzfeldt-Jakob disease
    Claudio Soto; Fiscal Year: 2013
    ..Second, PrPSc-specific monoclonal antibodies (called PrioC) raised against prion-infected brain homogenates in PrP knock out mice...
  10. NOVEL THERAPEUTICS FOR PRION DISEASES
    Stanley B Prusiner; Fiscal Year: 2013
    ..The accumulation of an alternatively folded isoform of the prion protein (PrPSc) in the brains of humans and animals is the hallmark of the prion disorders that include Creutzfeldt-..
  11. A new genetic approach for studying prions and other pathogenic protein aggregate
    Ann Hochschild; Fiscal Year: 2012
    ..The TSEs have been attributed to a specific cellular protein (PrP) that has the potential to convert to a highly structured, ? sheet-rich aggregated form (referred to as amyloid) ..
  12. A new genetic approach for studying prions and other pathogenic protein aggregate
    Ann Hochschild; Fiscal Year: 2011
    ..The TSEs have been attributed to a specific cellular protein (PrP) that has the potential to convert to a highly structured, ? sheet-rich aggregated form (referred to as amyloid) ..
  13. DEGENERATIVE AND DEMENTING DISEASES OF AGING
    Stanley B Prusiner; Fiscal Year: 2013
    ..Prions seem to be composed solely of PrPSc molecules, which are derived from a precursor PrPc by a poorly understood process...
  14. Origin and Mechanism of Promiscuous Prion Strains
    Surachai Supattapone; Fiscal Year: 2013
    ..likely to cross a species barrier if that cofactor is available by modulating the potential folding pathways for PrP molecules...
  15. Mechanisms of prion aggregation and species barriers
    Christina Sigurdson; Fiscal Year: 2013
    ..Our long term goal is to identify the key residues of the prion protein that govern species barriers and strain conformation...
  16. MURINE TRANSGENIC MODELS OF PRION DISEASES
    David A Harris; Fiscal Year: 2013
    ..we investigated how three, distinct genetic mechanisms (loss, gain, and subversion of the normal function of PrPC) contribute to neurodegeneration in two different transgenic models: Tg(PG14) mice, which express an aggregation-..
  17. CWD: A Model of Prion Transmission via Saliva and Urine
    NICHOLAS JAMES HALEY; Fiscal Year: 2013
    ..The results of these studies will contribute greatly to the understanding of pathogenesis and transmission potential of CWD, BSE, and vCJD. ..
  18. Transmissibility of Neurodegenerative Diseases
    DMITRY Y GOLDGABER; Fiscal Year: 2011
    ..It will also open new approaches and new opportunities in studying the pathological processes and in the development of new treatments of neurodegenerative diseases. ..
  19. Phosphorylation of Prion Protein as a novel mechanism for conversion
    Andrea C LeBlanc; Fiscal Year: 2010
    ..long-term objective of this proposal is to determine if phosphorylation is involved in normal or pathological prion protein (PrP) biology...
  20. Emergence of drug resistance in prion populations
    Roy G Smith; Fiscal Year: 2013
    ..they consist mainly, if not entirely of multimers of PrPSc, a conformational isomer of the host- encoded protein PrPC. Prions occur in the form of diverse strains, which differ in various phenotypic properties but whose PrPSc has the ..
  21. CNS DEGENERATION CAUSED BY NOVEL PATHOGENS
    STANLEY PRUSINER; Fiscal Year: 2002
    ..Investigation directed toward elucidating the molecular mechanism of conversion of the cellular prion protein) (PrP/c) into the scrapie isoform (PrP/sc) are proposed...
  22. Pathogenesis, Transmission and Detection of Zoonotic Prion Diseases (P01)
    Claudio Soto; Fiscal Year: 2012
    ..For these studies, we plan to generate and characterize knock in transgenic cattle expressing a PrP mutation recently identified in a natural BSE case in USA...
  23. Cyclic Amplification of Prion Protein Misfolding
    Claudio Soto; Fiscal Year: 2013
    ..This application is a competing renewal of a very successful project entitled "Cyclic Amplification of Prion Protein Misfolding"...
  24. Structural basis of species-specific infectivities of two prion strains
    Peter M Tessier; Fiscal Year: 2010
    ..Unfortunately, it is currently not possible to form highly infectious prions from recombinant mammalian prion protein (PrP) for structural studies, but this is readily possible for yeast prions...
  25. Towards Therapeutics for Neurodegenerative Diseases
    Stanley B Prusiner; Fiscal Year: 2013
    ..evidence showing that the most likely explanation for this therapeutic failure was a conformational change in PrP^*^ resulting in a drug-resistant prion strain...
  26. Investigation of the yeast prion factor [PSI+]
    Susan W Liebman; Fiscal Year: 2012
    ..In Aim IV the fascinating question of whether prions can sometimes provide the host cell with an advantage is explored, along with the possibility that such advantageous prions may also exist in mammals. ..
  27. Characterization of chaperone-prion specificity in Saccharomyces cerevisiae
    JUSTIN KEITH HINES; Fiscal Year: 2010
    ..which form a specific regulatory interaction in [RNQ+] prion maintenance: chaperones Sis1 and Ssa1, and the prion protein Rnq1. The specific aims are: 1...
  28. Self-Propagating Mechanism of Prion Diseases
    Ilia V Baskakov; Fiscal Year: 2013
    ....
  29. Therapeutic Approaches for Prion Disease
    Thomas M Wisniewski; Fiscal Year: 2013
    ..are infectious, conformational neurodegenerative disorders characterized by the structural modification of the prion protein, PrPC, into a pathological conformer, PrPSc...
  30. Elucidating factors involved in formation and propagation of yeast prion strains
    Kevin C Stein; Fiscal Year: 2012
    ..When the mammalian prion protein, PrP, adopts its prion conformation (PrPSc), it forms an infectious amyloid that causes fatal ..
  31. Structure and Mechanism of a Prion-remodeling Factor
    Francis T F Tsai; Fiscal Year: 2013
    ....
  32. Structural Characterization of Prion Isoforms in Multiple TSE Diseases
    MICHELE ANN MCGUIRL; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The goal of this research is to elucidate the structure of the prion protein in its aggregated isoforms, and to elucidate the relationship between isoform structure and different types of prion ..
  33. Elucidating molecular structure of mammalian prions
    Ilia V Baskakov; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prion protein (PrP) underlies a spectrum of diseases with no established treatment and devastating human and economic consequences...
  34. Elucidating molecular structure of mammalian prions
    Ilia V Baskakov; Fiscal Year: 2011
    b>Prion protein (PrP) underlies a spectrum of diseases with no established treatment and devastating human and economic consequences...
  35. Cross-seeding of Protein Misfolding as a Disease Mechanism
    Claudio Soto; Fiscal Year: 2013
    ....
  36. Elucidating the Relations of Heat Shock Factors, Molecular Chaperones and Prions
    Liming Li; Fiscal Year: 2012
    ..Wasting disease, the mechanisms responsible for the conversion of a normal cellular protein into an infectious prion protein continue to defy understanding...
  37. Mechanisms of prion transport
    Richard A Bessen; Fiscal Year: 2013
    ..Identification of the cellular pathways involved in prion transport can lead to the development of therapeutic interventions that can prevent disease dissemination. ..
  38. Absorption, Metabolism and Biodistribution of Prions after Oral Ingestion
    Claudio Soto; Fiscal Year: 2013
    ..The central pathogenic event is the conversion of the host-encoded prion protein (PrPC) into a misfolded isoform (PrPSc)...
  39. PMCA Detection of CWD Infection in Cervid and Non-Cervid Species
    EDWARD ARTHUR HOOVER; Fiscal Year: 2013
    ..Understanding how infectious misfolded proteins (prions) are generated, trafficked, shed, and transmitted will aid in preventing, treating, and managing the risks associated with these agents and the diseases they cause. ..
  40. UPTAKE, TRANSPORT, AND SPREAD OF PRIONS
    David A Harris; Fiscal Year: 2010
    Prion diseases are fatal neurodegenerative disorders of humans and animals. They result from conversion of PrPC, a normal membrane glycoprotein into PrPSc, a conformationally altered isoform that is infectious in the absence of nucleic ..
  41. ION CHANNEL MODULATION BY THE PRION PROTEIN: A NOVEL TOXIC MECHANISM
    David A Harris; Fiscal Year: 2013
    ..In contrast, how abnormal forms of the prion protein (PrP) kill nerve cells is still a mystery...
  42. A Prion Reveals Complex Traits and Phenotypic Diversity
    HEATHER L TRUE-KROB; Fiscal Year: 2013
    ..switch that is self-perpetuating and is transmitted from mother cells to their daughter cells when the prion protein is transmitted through the cytoplasm...
  43. Pathogenicity of prion protein aggregates from uninfected cells and brains
    Wen Quan Zou; Fiscal Year: 2013
    Project Summary A detergent-insoluble, partially proteinase K (PK)-resistant aggregated prion protein (PrPSc) constitutes the major component of prions that cause a group of fatal transmissible spongiform encephalopathies or prion ..
  44. Mechanisms of prion spread
    Christina Sigurdson; Fiscal Year: 2013
    ..by applicant): Prion diseases are fatal neurodegenerative disorders caused by an aggregated form of the prion protein, PrPSc...
  45. The Role of Competitive Forces in Prion Propagation and Appearance
    Tricia R Serio; Fiscal Year: 2013
    ..Through this unique perspective, we will begin to reveal the cellular pathways underlying transitions between prion-associated phenotypes, a crucial yet poorly understood aspect of prion biology. ..
  46. Elucidating the cellular mechanisms of prion propagation and clearance for devisi
    Donald L Jarvis; Fiscal Year: 2013
    ..diseases, and their pathogenesis is associated solely with aberrant misfolding of a single cellular protein (PrPc). Prion diseases are unique in this group as they are infectious disorders found in man and animals...
  47. Role of PrPc Polybasic domains in prion conversion
    Michael B Miller; Fiscal Year: 2013
    ..The infectious prion is largely or entirely composed of PrPSc, the misfolded isoform of the normal cellular protein PrPC. This project seeks to examine the role of polybasic domains (PBDs) in conversion of PrPC to PrPSc, the pivotal ..
  48. Mechanisms of prion strain selection
    Jason C Bartz; Fiscal Year: 2013
    ..by applicant): Prions are comprised of PrPSc, a misfolded isoform of the non-infectious host encoded protein, PrPC. Prion diseases are emerging zoonotic infectious diseases of mammals including humans...
  49. Synthetically generated mammalian prions
    Witold K Surewicz; Fiscal Year: 2013
    ..amplification (PMCA) protocol for generating highly infectious prions from bacterially expressed recombinant prion protein in the presence of well-defined cofactors offers unique opportunities to probe the molecular basis of prion ..
  50. A Proteomic Approach to Biomarker Discovery in Prion Disease
    Lingjun Li; Fiscal Year: 2009
    ..tests for prion disease have, thus far, focused on detection of the causal agent of the disease, the abnormal prion protein, or individual proteins that correlate with the neurological disease...
  51. Key molecular mechanisms of extraneural pathogenesis and transmission of TSEs
    Mark D Zabel; Fiscal Year: 2012
    ..deer and elk, scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jacob disease and kuru in humans...
  52. Replication mechanism of human prions
    Witold K Surewicz; Fiscal Year: 2013
    ..phenotypic variability of the disease suggests the existence of many different conformers of pathogenic prion protein (PrPSc) coding for distinct CJD prion strains...
  53. Molecular Pathogenesis of Age-Dependent CNS Regeneration
    Stanley B Prusiner; Fiscal Year: 2013
    ..neurons from human fibroblasts obtained from carriers with APP or PrP gene mutations that cause familial AD or CJD, respectively...
  54. In Vitro Dissection of Genetic Susceptibility to Prion Disease
    George A Carlson; Fiscal Year: 2011
    ..mice infected with the RML prion strain diluted 10-8 can infect neurospheres from transgenic mice overexpressing PrP, and the limits of sensitivity have not yet been reached...
  55. Conformational Conversions of Prion Protein
    Witold K Surewicz; Fiscal Year: 2013
    ..that the infectious pathogen responsible for these diseases is a misfolded, proteinase-resistant form of the prion protein, PrPSc, which is derived from a precursor PrPC by a poorly understood mechanism...
  56. Ubiquitin and regulation of prion induction by a short-lived protein
    Keith D Wilkinson; Fiscal Year: 2013
    ..Indeed, de novo formation of a yeast prion is promoted by overexpression of the prion protein and/or the presence of other aggregated QN-rich proteins...
  57. Defining the mechanistic basis of a prion disaggregase
    James Shorter; Fiscal Year: 2013
    ....
  58. Protein Conformational Switches
    Susan L Lindquist; Fiscal Year: 2013
    ..This work will provide fundamental new knowledge with potential applications to both normal biology and disease. ..
  59. Generation of Tau Prion Strains in Dividing Mammalian Cells
    DAVID WINLAND SANDERS; Fiscal Year: 2013
    ..research is significan because it could help lead to more accurate diagnosis of tauopathies, and to more precise antibody-based treatments that target extracellular protein, which are gaining increasing attention as potential therapies ..
  60. The determinants of aggregation and toxicity of prion-like domains
    Eric D Ross; Fiscal Year: 2013
    ..Finally, in Specific Aim 3, sophisticated bioinformatics methods will be used to incorporate this information into improved prediction algorithms, allowing for the identification of candidate disease-associated or regulatory PrLDs. ..
  61. Functional Diversity of J-protein Components of Hsp70 Chaperone Machinery
    Elizabeth A Craig; Fiscal Year: 2012
    ..In addition, we will investigate roles of molecular chaperones in the nucleus, focusing on novel regulatory functions independent of and separable from chaperone activity. ..
  62. Regulation of Amyloid Fibril Assembly by Hsp40 Molecular Chaperones
    Daniel W Summers; Fiscal Year: 2010
    ..This research will examine how cells regulate the assembly of protein aggregates into toxic or benign forms. ..
  63. Molecular basis of cell-specific prion strain propagation
    Charles Weissmann; Fiscal Year: 2010
    ..if not exclusively, of PrPSc, a multimer consisting of misfolded form(s) of the ubiquitous host glycoprotein PrPC. Replication of PrPSc is believed to follow the "seeding model", whereby infecting PrPSc accrues host PrPC ..
  64. Investigation of the Establishment of the Prion State
    Irina L Derkatch; Fiscal Year: 2010
    ..applicant): Prions cause tremendous concern as the causative agents of lethal neurodegenerative disorders such as CJD and BSE...
  65. MOLECULAR DETERMINANTS OF HUMAN PRION DISEASES
    James Mastrianni; Fiscal Year: 2000
    ..The C-terminus of PrPc is thought to bind to protein X, a putative molecular chaperone involved in the conversion of PrPc into PrPSc...
  66. Preventing Human Prion Diseases - Inactivation of Prions
    Stanley B Prusiner; Fiscal Year: 2010
    ..Effective protocols for inactivating prions will protect the general public as well as laboratory scientists who are investigating prions. Rarely does a research study have such immediate and important implications. ..
  67. MECHANISM OF CELL DEATH BY PRIONS
    Neena Singh; Fiscal Year: 2004
    ..is believed to result from a conformationally transformed, scrapie isoform (PrPSc) of the normal host prion protein (PrPC)...
  68. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
    ..No Abstract provided ..