scrapie

Summary

Summary: A fatal disease of the nervous system in sheep and goats, characterized by pruritus, debility, and locomotor incoordination. It is caused by proteinaceous infectious particles called PRIONS.

Top Publications

  1. ncbi RNA molecules stimulate prion protein conversion
    Nathan R Deleault
    Department of Biochemistry, 7200 Vail Building, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Nature 425:717-20. 2003
  2. ncbi Novel proteinaceous infectious particles cause scrapie
    S B Prusiner
    Science 216:136-44. 1982
  3. ncbi Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding
    G P Saborio
    Serono Pharmaceutical Research Institute, Geneva, Switzerland
    Nature 411:810-3. 2001
  4. ncbi In vitro generation of infectious scrapie prions
    Joaquin Castilla
    Department of Neurology, University of Texas Medical Branch, Galveston, Texas 77555, USA
    Cell 121:195-206. 2005
  5. pmc Formation of native prions from minimal components in vitro
    Nathan R Deleault
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Proc Natl Acad Sci U S A 104:9741-6. 2007
  6. ncbi Marked influence of the route of infection on prion strain apparent phenotype in a scrapie transgenic mouse model
    Christelle Langevin
    INRA Institut National de la recherche Agronomique, UR892, Virologie Immunologie Moléculaires, F 78350 Jouy en Josas, France
    Neurobiol Dis 41:219-25. 2011
  7. pmc Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins
    K M Pan
    Department of Neurology, University of California, San Francisco 94143
    Proc Natl Acad Sci U S A 90:10962-6. 1993
  8. pmc Prionemia and leukocyte-platelet-associated infectivity in sheep transmissible spongiform encephalopathy models
    Caroline Lacroux
    UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Veterinaire de Toulouse, Toulouse, France
    J Virol 86:2056-66. 2012
  9. pmc Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie
    A J Raeber
    Institut fur Molekularbiologie, Abteilung I, University of Zurich, H onggerberg, 8093 Z urich, Switzerland
    EMBO J 16:6057-65. 1997
  10. pmc Accumulation and dissemination of prion protein in experimental sheep scrapie in the natural host
    Stephen J Ryder
    Department of Pathology, Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey KT153NB, UK
    BMC Vet Res 5:9. 2009

Detail Information

Publications368 found, 100 shown here

  1. ncbi RNA molecules stimulate prion protein conversion
    Nathan R Deleault
    Department of Biochemistry, 7200 Vail Building, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Nature 425:717-20. 2003
    ..They also provide a practical approach to improve the sensitivity of diagnostic techniques based on PrPres amplification...
  2. ncbi Novel proteinaceous infectious particles cause scrapie
    S B Prusiner
    Science 216:136-44. 1982
    After infection and a prolonged incubation period, the scrapie agent causes a degenerative disease of the central nervous system in sheep and goats...
  3. ncbi Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding
    G P Saborio
    Serono Pharmaceutical Research Institute, Geneva, Switzerland
    Nature 411:810-3. 2001
    ....
  4. ncbi In vitro generation of infectious scrapie prions
    Joaquin Castilla
    Department of Neurology, University of Texas Medical Branch, Galveston, Texas 77555, USA
    Cell 121:195-206. 2005
    ..Inoculation of wild-type hamsters with in vitro-produced PrPres led to a scrapie disease identical to the illness produced by brain infectious material...
  5. pmc Formation of native prions from minimal components in vitro
    Nathan R Deleault
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Proc Natl Acad Sci U S A 104:9741-6. 2007
    ..appears to play a critical role in the pathogenesis of prion diseases such as Creutzfeldt-Jakob disease and scrapie. However, the fundamental mechanism by which infectious prions are produced in neurons remains unknown...
  6. ncbi Marked influence of the route of infection on prion strain apparent phenotype in a scrapie transgenic mouse model
    Christelle Langevin
    INRA Institut National de la recherche Agronomique, UR892, Virologie Immunologie Moléculaires, F 78350 Jouy en Josas, France
    Neurobiol Dis 41:219-25. 2011
    ..this possibility, we studied prion pathogenesis in a prototypal short-incubation disease model consisting of 127S scrapie strain propagated in tg338 transgenic mice expressing the VRQ allele of ovine PrP...
  7. pmc Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins
    K M Pan
    Department of Neurology, University of California, San Francisco 94143
    Proc Natl Acad Sci U S A 90:10962-6. 1993
    Prions are composed largely, if not entirely, of prion protein (PrPSc in the case of scrapie)...
  8. pmc Prionemia and leukocyte-platelet-associated infectivity in sheep transmissible spongiform encephalopathy models
    Caroline Lacroux
    UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Veterinaire de Toulouse, Toulouse, France
    J Virol 86:2056-66. 2012
    ..Using two distinct sheep scrapie models and blood transfusion, this work demonstrates the occurrence of a very early and persistent prionemia...
  9. pmc Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie
    A J Raeber
    Institut fur Molekularbiologie, Abteilung I, University of Zurich, H onggerberg, 8093 Z urich, Switzerland
    EMBO J 16:6057-65. 1997
    ..After inoculation with hamster scrapie, these mice accumulated infectivity and PrPSc to high levels, developed severe disease after 227 +/- 5 days and ..
  10. pmc Accumulation and dissemination of prion protein in experimental sheep scrapie in the natural host
    Stephen J Ryder
    Department of Pathology, Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey KT153NB, UK
    BMC Vet Res 5:9. 2009
    In order to study the sites of uptake and mechanisms of dissemination of scrapie prions in the natural host under controlled conditions, lambs aged 14 days and homozygous for the VRQ allele of the PrP gene were infected by the oral route...
  11. 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...
  12. pmc Strain-specified relative conformational stability of the scrapie prion protein
    D Peretz
    Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94143, USA
    Protein Sci 10:854-63. 2001
    ..Based on these results, the eight prion strains segregated into four distinct groups. Our results support the unorthodox proposal that distinct PrP(Sc) conformers encipher the biological properties of prion strains...
  13. pmc The physical relationship between infectivity and prion protein aggregates is strain-dependent
    Philippe Tixador
    INRA Institut National de la recherche Agronomique, UR892, Virologie Immunologie Moléculaires, Jouy en Josas, France
    PLoS Pathog 6:e1000859. 2010
    ..to a panel of natural, biologically cloned strains obtained by propagation of classical and atypical sheep scrapie and BSE infectious sources in transgenic mice expressing ovine PrP...
  14. ncbi Strain typing of German transmissible spongiform encephalopathies field cases in small ruminants by biochemical methods
    A Gretzschel
    Friedrich Loeffler Institut FLI, Institute for Novel and Emerging Diseases, Insel Riems, Germany
    J Vet Med B Infect Dis Vet Public Health 52:55-63. 2005
    ..In this national survey, 186 scrapie-affected sheep were found which originated from 78 flocks...
  15. ncbi In vitro amplification of PrPSc derived from the brain and blood of sheep infected with scrapie
    Leigh Thorne
    Department of Molecular Pathogenesis and Genetics, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey KT15 3NB, UK
    J Gen Virol 89:3177-84. 2008
    b>Scrapie is a fatal, naturally transmissible, neurodegenerative prion disease that affects sheep and goats and is characterized by the accumulation of a misfolded protein, PrPSc, converted from host-encoded PrPc, in the central nervous ..
  16. ncbi Strain characterization of natural sheep scrapie and comparison with BSE
    Moira E Bruce
    Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK
    J Gen Virol 83:695-704. 2002
    b>Scrapie was transmitted to mice from ten sheep, collected in the UK between 1985 and 1994...
  17. ncbi Isolation and characterization of a proteinase K-sensitive PrPSc fraction
    Miguel A Pastrana
    Prion Research Unit, Department of Medicine, School of Medicine, University of Santiago de Compostela, Rue de S Francisco s n, Santiago de Compostela, Galiza, Spain 15782
    Biochemistry 45:15710-7. 2006
    ..PK-sensitive PrPSc isolates should prove useful for structural studies to help understand fundamental issues of the molecular biology of PrPSc and in the quest to design tests to detect preclinical prion disease...
  18. pmc Follicular dendritic cell dedifferentiation by treatment with an inhibitor of the lymphotoxin pathway dramatically reduces scrapie susceptibility
    Neil A Mabbott
    Neuropathogenesis Unit, Institute for Animal Health, Edinburgh EH9 3JF, Scotland, United Kingdom
    J Virol 77:6845-54. 2003
    ..Studies of mouse scrapie models have shown that mature follicular dendritic cells (FDCs), expressing the host prion protein (PrP(c)), are ..
  19. pmc Highly efficient protein misfolding cyclic amplification
    Nuria Gonzalez-Montalban
    Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, Maryland, United States of America
    PLoS Pathog 7:e1001277. 2011
    ..Using serial PMCAb, a 10¹²-fold dilution of scrapie brain material could be amplified to the level detectible by Western blotting in 3 rounds (72 hours)...
  20. ncbi Prion diseases are efficiently transmitted by blood transfusion in sheep
    Fiona Houston
    Neuropathogenesis Division, Roslin Institute, Compton, United Kingdom
    Blood 112:4739-45. 2008
    ..We previously reported preliminary data demonstrating the transmission of BSE and natural scrapie by blood transfusion in sheep...
  21. ncbi Conformational transitions, dissociation, and unfolding of scrapie amyloid (prion) protein
    J Safar
    Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892
    J Biol Chem 268:20276-84. 1993
    The infectious form of the scrapie amyloid (prion) precursor, PrPSc, is a host-derived protein and a component of the infectious agent causing scrapie...
  22. ncbi Sympathetic innervation of lymphoreticular organs is rate limiting for prion neuroinvasion
    M Glatzel
    Institute of Neuropathology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland
    Neuron 31:25-34. 2001
    ..Following intraperitoneal prion inoculation, chemical or immunological sympathectomy delayed or prevented scrapie. Prion titers in spinal cords were drastically reduced at early time points after inoculation...
  23. 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
    ..physiological conditions was used, which contained purified DRMs as a source of PrP-sen and brain microsomes from scrapie-infected mice as a source of PrP-res...
  24. ncbi Mice devoid of PrP are resistant to scrapie
    H Bueler
    Institut für Molekularbiologie I, Universitat Zurich, Switzerland
    Cell 73:1339-47. 1993
    ..Prn-p0/0 mice devoid of PrPC showed normal development and behavior. When inoculated with mouse scrapie prions, they remained free of scrapie symptoms for at least 13 months while wild-type controls all died within 6 ..
  25. pmc Proteinase K-resistant material in ARR/VRQ sheep brain affected with classical scrapie is composed mainly of VRQ prion protein
    J G Jacobs
    Central Veterinary Institute of Wageningen UR CVI, P O Box 65, 8200 AB Lelystad, The Netherlands
    J Virol 85:12537-46. 2011
    Classical scrapie is a prion disease in sheep and goats. In sheep, susceptibility to disease is genetically influenced by single amino acid substitutions...
  26. ncbi PrP(Sc) detection and infectivity in semen from scrapie-infected sheep
    Richard Rubenstein
    Department of Neurology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA
    J Gen Virol 93:1375-83. 2012
    A scrapie-positive ewe was found in a flock that had been scrapie-free for 13 years, but housed adjacent to scrapie-positive animals, separated by a wire fence...
  27. pmc Susceptibility to scrapie and disease phenotype in sheep: cross-PRNP genotype experimental transmissions with natural sources
    Lorenzo Gonzalez
    Animal Health and Veterinary Laboratories Agency, Pentlands Science Park, Bush Loan, Midlothian, EH26 0PZ, United Kingdom
    Vet Res 43:55. 2012
    It has long been established that the sheep Prnp genotype influences the susceptibility to scrapie, and some studies suggest that it can also determine several aspects of the disease phenotype...
  28. pmc Prion seeding activities of mouse scrapie strains with divergent PrPSc protease sensitivities and amyloid plaque content using RT-QuIC and eQuIC
    Sarah Vascellari
    Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
    PLoS ONE 7:e48969. 2012
    ..b>Scrapie brain dilutions up to 10(-8) and 10(-13) were detected by RT-QuIC and eQuIC, respectively...
  29. ncbi Transportation of prion protein across the intestinal mucosa of scrapie-susceptible and scrapie-resistant sheep
    M Jeffrey
    Veterinary Laboratories Agency VLA Lasswade, Pentlands Science Park, Midlothian, UK
    J Pathol 209:4-14. 2006
    To determine the mechanisms of intestinal transport of infection, and early pathogenesis, of sheep scrapie, isolated gut-loops were inoculated to ensure that significant concentrations of scrapie agent would come into direct contact with ..
  30. pmc Sheep with scrapie and mastitis transmit infectious prions through the milk
    Ciriaco Ligios
    Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy
    J Virol 85:1136-9. 2011
    ..Here, we show that sheep with scrapie and lentiviral mastitis secrete prions into the milk and infect nearly 90% of naïve suckling lambs...
  31. 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
    ..these issues we have taken a combination of pharmacological and genetic approaches using persistently infected scrapie mouse brain (SMB) cells...
  32. pmc Prion disease detection, PMCA kinetics, and IgG in urine from sheep naturally/experimentally infected with scrapie and deer with preclinical/clinical chronic wasting disease
    Richard Rubenstein
    SUNY Downstate Medical Center, Department of Neurology, Box 1213, 450 Clarkson Avenue, Brooklyn, NY 11203, USA
    J Virol 85:9031-8. 2011
    ..prion disease-associated seeding activity (PASA) in urine from naturally and orally infected sheep with clinical scrapie agent and orally infected preclinical and infected white-tailed deer with clinical chronic wasting disease (CWD)...
  33. ncbi Propagation of ovine prions from "poor" transmitter scrapie isolates in ovine PrP transgenic mice
    Alana M Thackray
    University of Cambridge, Department of Veterinary Medicine, Madingley Road, Cambridge, CB3 OES, UK
    Exp Mol Pathol 92:167-74. 2012
    ..The existence of scrapie isolates that do not propagate in wild type mice, defined here as "poor" transmitters, are problematic for ..
  34. ncbi Emergence of multiple prion strains from single isolates of ovine scrapie
    Alana M Thackray
    University of Cambridge, Department of Veterinary Medicine, Cambridge, UK
    J Gen Virol 92:1482-91. 2011
    The infectious agent associated with prion diseases such as ovine scrapie shows strain diversity. Ovine prion strains have typically been identified by their transmission properties in wild-type mice...
  35. ncbi Neuroinvasion in sheep transmissible spongiform encephalopathies: the role of the haematogenous route
    S Siso
    Department of Pathology, Veterinary Laboratories Agency, Bush Loan, Penicuik, Midlothian, UK
    Neuropathol Appl Neurobiol 35:232-46. 2009
    ....
  36. pmc The natural atypical scrapie phenotype is preserved on experimental transmission and sub-passage in PRNP homologous sheep
    Marion M Simmons
    Department of Pathology, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone KT15 3NB, UK
    BMC Vet Res 6:14. 2010
    Atypical scrapie was first identified in Norwegian sheep in 1998 and has subsequently been identified in many countries...
  37. pmc Atypical/Nor98 scrapie infectivity in sheep peripheral tissues
    Olivier Andreoletti
    UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Veterinaire de Toulouse, Toulouse, France
    PLoS Pathog 7:e1001285. 2011
    Atypical/Nor98 scrapie was first identified in 1998 in Norway...
  38. pmc State-of-the-art review of goat TSE in the European Union, with special emphasis on PRNP genetics and epidemiology
    Gabriele Vaccari
    Department of Food Safety and Veterinary Public Health, Unit of Transmissible Spongiform Encephalopathies and Emerging Infectious Diseases of Animals, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161, Rome, Italy
    Vet Res 40:48. 2009
    b>Scrapie is a fatal, neurodegenerative disease of sheep and goats...
  39. ncbi PrP gene polymorphisms in Cyprus goats and their association with resistance or susceptibility to natural scrapie
    Penelope Papasavva-Stylianou
    TSE Section, Laboratory of Animal Health, State Veterinary Laboratories, Veterinary Services, 1417 Nicosia, Cyprus
    Vet J 187:245-50. 2011
    In contrast to scrapie in sheep, the genetic basis of susceptibility to scrapie in goats is not well understood...
  40. 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
    ..By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission...
  41. pmc Prion strain discrimination in cell culture: the cell panel assay
    Sukhvir P Mahal
    Department of Infectology, Scripps Florida, 5353 Parkside Drive, Jupiter, FL 33458, USA
    Proc Natl Acad Sci U S A 104:20908-13. 2007
    ..lines, N2a-PK1, N2a-R33, LD9 and CAD5, which show widely different responses to prion strains RML, 22L, 301C, and Me7, into a panel that allows their discrimination in vitro within 2 weeks, using the standard scrapie cell assay (SSCA).
  42. pmc Microglial cell line established from prion protein-overexpressing mice is susceptible to various murine prion strains
    Yoshifumi Iwamaru
    Research Center for Prion Diseases, National Institute of Animal Health, Kannondai 3 1 5, Tsukuba, Ibaraki 305 8602, Japan
    J Virol 81:1524-7. 2007
    ..After exposure to Chandler scrapie, we observed the replication and accumulation of disease-associated forms of the prion protein in MG20 cells up ..
  43. pmc Lesion profiling at primary isolation in RIII mice is insufficient in distinguishing BSE from classical scrapie
    Katy E Beck
    Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, Surrey KT15 3NB, UK
    Brain Pathol 20:313-22. 2010
    ..in RIII mice generates a lesion profile believed to be reproducible and distinct from that produced by classical scrapie. This profile, which is characterized by peaks at gray matter areas 1, 4 and 7 (dorsal medulla, hypothalamus and ..
  44. ncbi Ovine PrP genotype is linked with lesion profile and immunohistochemistry patterns after primary transmission of classical scrapie to wild-type mice
    Katy E Beck
    Neuropathology Unit, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, Surrey, United Kingdom
    J Neuropathol Exp Neurol 69:483-97. 2010
    It is currently believed that primary transmission of classical scrapie to wild-type mice is inefficient and characterized by low attack rates and variable incubation periods and lesion profiles...
  45. pmc Proteinase K-sensitive disease-associated ovine prion protein revealed by conformation-dependent immunoassay
    Alana M Thackray
    Centre for Veterinary Science, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 OES, UK
    Biochem J 401:475-83. 2007
    ..utilizing time-resolved fluorescence to study the conformers of disease-associated PrP in natural cases of sheep scrapie, without using PK (proteinase K) treatment to discriminate between PrPC and PrPSc...
  46. pmc Oral prion infection requires normal numbers of Peyer's patches but not of enteric lymphocytes
    Marco Prinz
    Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    Am J Pathol 162:1103-11. 2003
    ..Although susceptibility to prion infection following oral challenge correlates with the number of PPs, it is remarkably independent of the number of PP-associated lymphocytes...
  47. pmc Faecal shedding, alimentary clearance and intestinal spread of prions in hamsters fed with scrapie
    Dominique Krüger
    Robert Koch Institute, P24 Transmissible Spongiform Encephalopathies, Nordufer 20, D 13353 Berlin, Germany
    Vet Res 40:4. 2009
    ..Here, we fed hamsters 10mg of 263K scrapie brain homogenate and examined the faecal excretion of disease-associated prion protein (PrP(TSE)) during the ..
  48. ncbi Novel polymorphisms at codons 146 and 151 in the prion protein gene of Cyprus goats, and their association with natural scrapie
    Penelope Papasavva-Stylianou
    Virology Laboratory, Veterinary Services, 1417 Nicosia, Cyprus
    Vet J 173:459-62. 2007
    ..an association exists between specific combinations of polymorphisms of the prion protein (PrP) and natural scrapie in Cyprus goats, 250 goats were examined, including 164 histologically positive cases...
  49. ncbi Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis
    Giovanna Mallucci
    Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1, UK
    Science 302:871-4. 2003
    ..Thus, the propagation of nonneuronal PrPSc is not pathogenic, but arresting the continued conversion of PrPc to PrPSc within neurons during scrapie infection prevents prion neurotoxicity.
  50. pmc Medulla oblongata transcriptome changes during presymptomatic natural scrapie and their association with prion-related lesions
    Hicham Filali
    Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain
    BMC Genomics 13:399. 2012
    The pathogenesis of natural scrapie and other prion diseases is still poorly understood...
  51. ncbi Scrapie-like prion protein is translocated to the nuclei of infected cells independently of proteasome inhibition and interacts with chromatin
    Alain Mangé
    Institut de Genetique Humaine, UPR CNRS1142, 141 Rue de la Cardonille 34396 Montpellier CEDEX 5, France
    J Cell Sci 117:2411-6. 2004
    ..Moreover, our results show for the first time that nuclear PrP interacts with chromatin in vivo, which may have physiopathological consequences in prion diseases..
  52. 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
    ..The transmissible agent (prion) responsible for scrapie is believed to be a modified form of PrPC. Mice homozygous for disrupted PrP genes have been generated...
  53. ncbi Immunolocalisation of PrPSc in scrapie-infected N2a mouse neuroblastoma cells by light and electron microscopy
    Nathalie M Veith
    Molecular Toxicology, Department of Biology, University of Konstanz, Box X911, D 78457 Konstanz, Germany
    Eur J Cell Biol 88:45-63. 2009
    ..Here we describe the localisation of PrPC and PrPSc in a scrapie-infected neuroblastoma cell line, ScN2a, by light and electron microscopic immunolocalisation...
  54. pmc Resistance to classical scrapie in experimentally challenged goats carrying mutation K222 of the prion protein gene
    Pier Luigi Acutis
    CEA, Italian Reference Laboratory for TSEs, Neuroscienze Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d Aosta, Via Bologna 148, 10154 Torino, Italy
    Vet Res 43:8. 2012
    Susceptibility of sheep to scrapie, a transmissible spongiform encephalopathy of small ruminants, is strongly influenced by polymorphisms of the prion protein gene (PRNP)...
  55. ncbi A trans-dominant negative 37kDa/67kDa laminin receptor mutant impairs PrP(Sc) propagation in scrapie-infected neuronal cells
    Karen Vana
    Laboratorium für Molekulare Biologie Genzentrum Institut für Biochemie der LMU München, Feodor Lynen Strasse 25, D 81377 Munich, Germany
    J Mol Biol 358:57-66. 2006
    ..mouse neuroblastoma cells, and infectious moPrP27-30 to BHK cells, and interferes with the PrP(Sc) propagation in scrapie-infected neuroblastoma cells (N2aSc(+))...
  56. pmc Isolation of prion with BSE properties from farmed goat
    John Spiropoulos
    Animal Health and Veterinary Laboratories Agency, Weybridge, Surrey, UK
    Emerg Infect Dis 17:2253-61. 2011
    ..encephalopathies are fatal neurodegenerative diseases that include variant Creutzfeldt-Jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (BSE) in cattle...
  57. pmc Direct evidence of generation and accumulation of β-sheet-rich prion protein in scrapie-infected neuroblastoma cells with human IgG1 antibody specific for β-form prion protein
    Toshiya Kubota
    Department of Chemistry, Biotechnology, and Chemical Engineering, Graduate School of Science and Engineering, Kagoshima University, Kagoshima 890 0065, Japan
    J Biol Chem 287:14023-39. 2012
    ..PRB7 is the first human antibody specific to β-form PrP and has become a powerful tool for the characterization of the biochemical nature of prion and its pathology...
  58. ncbi Immunohistochemical distinction between preclinical bovine spongiform encephalopathy and scrapie infection in sheep
    C M A Thuring
    Department of Animal Husbandry and Production, Faculty of Veterinary Medicine, University College Dublin, Ballsbridge, Dublin 4, Ireland
    J Comp Pathol 132:59-69. 2005
    ..to bovine spongiform encephalopathy (BSE), the clinical signs being indistinguishable from those of scrapie. Because of the possibility of natural ovine BSE infection, laboratory tests are needed to distinguish between ..
  59. pmc The 37 kDa/67 kDa laminin receptor is required for PrP(Sc) propagation in scrapie-infected neuronal cells
    Christoph Leucht
    Laboratorium für Molekulare Biologie Genzentrum Institut für Biochemie der LMU München, Feodor Lynen Str 25, D 81377 Munich, Germany
    EMBO Rep 4:290-5. 2003
    The accumulation of PrP(Sc) in scrapie-infected neuronal cells has been prevented by three approaches: (i) transfection of ScMNB cells with an antisense laminin receptor precursor (LRP) RNA-expression plasmid, (ii) transfection of ScN2a ..
  60. pmc Use of murine bioassay to resolve ovine transmissible spongiform encephalopathy cases showing a bovine spongiform encephalopathy molecular profile
    Katy E Beck
    Animal Health and Veterinary Laboratories Agency, Addlestone, Surrey, UK
    Brain Pathol 22:265-79. 2012
    ..on the same farm in ARQ/ARQ PrP sheep showing attributes of both bovine spongiform encephalopathy (BSE) and scrapie. These cases, UK-1 and UK-2, were investigated further by transmissions to wild-type and ovine transgenic mice...
  61. ncbi Ultrastructures and strain comparison of under-glycosylated scrapie prion fibrils
    Valerie L Sim
    Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, United States
    Neurobiol Aging 30:2031-42. 2009
    ..visualization of their fibrillar cores, so we purified severely under-glycosylated prion protein fibrils from scrapie-infected transgenic mice expressing anchorless prion protein...
  62. pmc Assessment of the genetic susceptibility of sheep to scrapie by protein misfolding cyclic amplification and comparison with experimental scrapie transmission studies
    Cecilia Bucalossi
    Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy
    J Virol 85:8386-92. 2011
    The susceptibility of sheep to scrapie is influenced mainly by the prion protein polymorphisms A136V, R154H, and Q171R/H...
  63. pmc Quantitative detection and biological propagation of scrapie seeding activity in vitro facilitate use of prions as model pathogens for disinfection
    Sandra Pritzkow
    Transmissible Spongiform Encephalopathies, Project Group Immune Defense and Pathogenesis, Robert Koch Institut, Berlin, Germany
    PLoS ONE 6:e20384. 2011
    ..Here we report on the development of a methodological platform that further facilitates the use of scrapie prions as model pathogens for disinfection...
  64. ncbi Infectious titres of sheep scrapie and bovine spongiform encephalopathy agents cannot be accurately predicted from quantitative laboratory test results
    Lorenzo Gonzalez
    Animal Health and Veterinary Laboratories Agency AHVLA, AHVLA Lasswade, Pentlands Science Park, Penicuick, Midlothian EH26 0PZ, UK
    J Gen Virol 93:2518-27. 2012
    ..To address this discrepancy, 11 brain samples of sheep affected with natural scrapie or experimental bovine spongiform encephalopathy were selected on the basis of the magnitude and predominant ..
  65. pmc Propagation of RML prions in mice expressing PrP devoid of GPI anchor leads to formation of a novel, stable prion strain
    Sukhvir Paul Mahal
    Department of Infectology, Scripps Florida, Jupiter, Florida, United States of America
    PLoS Pathog 8:e1002746. 2012
    ..Because both RML PrP(Sc) and SFL PrP(Sc) are stably propagated in wild-type mice we propose that the two conformations are separated by a high activation energy barrier which is abrogated in tgGPI⁻ mice...
  66. pmc PK-sensitive PrP is infectious and shares basic structural features with PK-resistant PrP
    Gustavo Sajnani
    Department of Medicine, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Galiza, Spain
    PLoS Pathog 8:e1002547. 2012
    ..Although the sPrP(Sc) and rPrP(Sc) fractions have different resistance to PK-digestion, and have previously been shown to sediment differently, and have a different distribution of multimers, they share a common structure and phenotype...
  67. ncbi Specific inhibition of pathological prion protein accumulation by small interfering RNAs
    Nathalie Daude
    Institut de Pharmacologie Moleculaire et Cellulaire, Unité Mixte de Recherche 6097, Centre National de la Recherche Scientifique 660, route des Lucioles, 06560 Valbonne, France
    J Cell Sci 116:2775-9. 2003
    ..the present report, we show that small interfering RNA (siRNA) duplexes trigger specific Prnp gene silencing in scrapie-infected neuroblastoma cells...
  68. pmc Isolation of proteinase K-sensitive prions using pronase E and phosphotungstic acid
    Laura D'Castro
    MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom
    PLoS ONE 5:e15679. 2010
    ..This procedure now allows characterization of proteinase K-sensitive prions and investigation of their clinical relevance in human and animal prion disease without being confounded by contaminating PrP(C)...
  69. ncbi Mice with gene targetted prion protein alterations show that Prnp, Sinc and Prni are congruent
    R C Moore
    Institute of Cell and Molecular Biology, University of Edinburgh, UK
    Nat Genet 18:118-25. 1998
    Classical genetic analysis has identified Sinc/Prni as the major gene controlling mouse scrapie incubation time. Sinc/Prni is linked to Prnp, the gene encoding the prion protein (PrP)...
  70. ncbi Post-mortem immunodiagnosis of scrapie and bovine spongiform encephalopathy
    C F Farquhar
    Institute for Animal Health, AFRC and MRC Neuropathogenesis Unit, Edinburgh
    J Virol Methods 24:215-21. 1989
    Two polyclonal antisera were raised in rabbits against the scrapie-associated fibril protein (PrP) prepared from sheep and mice which were terminally infected with experimental scrapie...
  71. pmc Scrapie infectivity in hamster blood is not associated with platelets
    Karel Holada
    Laboratory of Cellular Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA
    J Virol 76:4649-50. 2002
    The infectivity of hamster scrapie strain 263K was measured in platelets isolated from blood pooled from six hamsters with clinical scrapie. The total number of infectious doses present in the blood pool was 220, out of which only 3...
  72. pmc The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt-Jakob disease and scrapie agents
    Laura Manuelidis
    Section of Neuropathology, Yale University Medical School, 333 Cedar Street, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 106:13529-34. 2009
    Human sporadic Creutzfeldt-Jakob disease (sCJD), endemic sheep scrapie, and epidemic bovine spongiform encephalopathy (BSE) are caused by a related group of infectious agents. The new U.K...
  73. ncbi Prions are secreted into the oral cavity in sheep with preclinical scrapie
    Ben C Maddison
    ADAS UK, Department of Biology, University of Leicester, Leicestershire, United Kingdom
    J Infect Dis 201:1672-6. 2010
    ..We analyzed buccal swab samples obtained from preclinical scrapie-infected sheep by concentrating the collected prions on silicon dioxide, followed by amplification by serial ..
  74. 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
    ..the cellular location of disease-specific co-factors using fractions derived from gradient centrifugation of a scrapie-susceptible cell line...
  75. ncbi Three serial passages of bovine spongiform encephalopathy in sheep do not significantly affect discriminatory test results
    Michael Stack
    Veterinary Laboratories Agency VLA, Woodham Lane, Addlestone, Surrey, UK
    J Gen Virol 90:764-8. 2009
    ..techniques, Western immunoblotting (WB) and immunohistochemistry (IHC), have been developed to distinguish scrapie from cases of experimental sheep BSE by the characteristics of their respective abnormal, disease-associated ..
  76. ncbi Effect of scrapie on the stability of housekeeping genes
    J Lyahyai
    Laboratorio de Genetica Bioquimica LAGENBIO, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain
    Anim Biotechnol 21:1-13. 2010
    b>Scrapie is the archetype of prion diseases, fatal neurodegenerative disorders that affect humans and animals...
  77. ncbi Caprine PRNP polymorphisms at codons 171, 211, 222 and 240 in a Greek herd and their association with classical scrapie
    Ilias G Bouzalas
    Laboratory of Microbiology and Infectious Diseases, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
    J Gen Virol 91:1629-34. 2010
    The association between PRNP variation and scrapie incidence was investigated in a highly affected Greek goat herd. Four mutations were identified at codons 171Q/R, 211R/Q, 222Q/K and 240P/S...
  78. ncbi Molecular biology and pathology of scrapie and the prion diseases of humans
    S B Prusiner
    Department of Neurology, University of California, San Francisco 94143
    Brain Pathol 1:297-310. 1991
    b>Scrapie and bovine spongiform encephalopathy of animals and Creutzfeldt-Jakob and Gerstmann-Sträussler-Scheinker diseases of humans are transmissible and genetic neurodegenerative diseases caused by prions...
  79. ncbi PrPSc accumulation in fetal cotyledons of scrapie-resistant lambs is influenced by fetus location in the uterus
    Janet Alverson
    USDA, ARS, Animal Disease Research Unit, 3003 ADBF, Washington State University, Pullman, WA 99164, USA
    J Gen Virol 87:1035-41. 2006
    Placentae from scrapie-infected ewes have been shown to accumulate PrPSc when the genotype of the fetus is of a susceptible genotype (VRQ/VRQ, ARQ/VRQ or ARQ/ARQ)...
  80. ncbi Prion protein allele A136 H154Q171 is associated with high susceptibility to scrapie in purebred and crossbred German Merinoland sheep
    G Luhken
    Department of Animal Breeding and Genetics, Justus Liebig University, Giessen, Germany
    Arch Virol 149:1571-80. 2004
    Prion protein (PrP) genotypes were determined in eight sheep that have been tested positive for atypical scrapie from purebred or crossbred Merinoland sheep flocks in Germany and compared with the PrP genotypes of their flock mates...
  81. ncbi Occurrence and distribution of infection-specific PrP in tissues of clinical scrapie cases and cull sheep from scrapie-affected farms in Shetland
    M Jeffrey
    Veterinary Laboratories Agency Lasswade, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, UK
    J Comp Pathol 127:264-73. 2002
    The prion protein (PrP) genotypes of all cull sheep originating from four scrapie-affected farms in Shetland in 1998-1999 were determined and a representative sample of the different genotypes was selected for necropsy...
  82. ncbi Protease-sensitive scrapie prion protein in aggregates of heterogeneous sizes
    Salit Tzaban
    Department of Molecular Biology, The Hebrew University Hadassah Medical School, and Hadassah University Hospital, Jerusalem 91120, Israel
    Biochemistry 41:12868-75. 2002
    ..The small PrP(Sc) aggregates described here are consistent with the previous demonstration of scrapie infectivity in brain fractions with a sedimentation coefficient as small as 40 S [Prusiner et al. (1980) J...
  83. pmc Transmission barriers for bovine, ovine, and human prions in transgenic mice
    Michael R Scott
    Institute for Neurodegenerative Diseases, University of California, San Francisco, 94143 0518, USA
    J Virol 79:5259-71. 2005
    ..These mice also posed no transmission barrier for Suffolk sheep scrapie prions, suggesting that cattle may be highly susceptible to some sheep scrapie strains...
  84. ncbi Biochemistry and structure of PrP(C) and PrP(Sc)
    Detlev Riesner
    , , , Germany
    Br Med Bull 66:21-33. 2003
    ..it is shown that the prion model was developed from the biochemical and biophysical properties of the scrapie infectious agent...
  85. 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
    ..only anchorless PrP, we found that PrP anchoring to the cell membrane was required for typical clinical scrapie. However, in the present experiments, using homozygous transgenic mice expressing two-fold more anchorless PrP, ..
  86. 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
    ..Disruption of the PrP gene in the mouse abolishes susceptibility to scrapie and prion replication...
  87. pmc Sheep-passaged bovine spongiform encephalopathy agent exhibits altered pathobiological properties in bovine-PrP transgenic mice
    Juan Carlos Espinosa
    Centro de Investigacion en Sanidad Animal, INIA, 28130 Valdeolmos, Madrid, Spain
    J Virol 81:835-43. 2007
    ..can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern...
  88. 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 mice are being used in experiments designed to address the role of PrP in the pathogenesis of scrapie and the replication of infectivity.
  89. pmc Lentivector-mediated RNAi efficiently suppresses prion protein and prolongs survival of scrapie-infected mice
    Alexander Pfeifer
    Institute of Pharmacology and Toxicology, University of Bonn, Bonn, Germany
    J Clin Invest 116:3204-10. 2006
    ..Treatment of scrapie-infected neuronal cells with these lentivectors resulted in an efficient and stable suppression of PrP(Sc) ..
  90. pmc Disease dynamics over very different time-scales: foot-and-mouth disease and scrapie on the network of livestock movements in the UK
    Rowland R Kao
    Department of Zoology, University of Oxford, Oxford OX1 3PS, UK
    J R Soc Interface 4:907-16. 2007
    ..UK and the dynamics of two diseases: foot-and-mouth disease (FMD), which has an incubation period of days, and scrapie, which incubates over years...
  91. ncbi Efficient in vitro amplification of a mouse-adapted scrapie prion protein
    Yuichi Murayama
    Prion Disease Research Center, National Institute of Animal Health, 3 1 5 Kannondai, Tsukuba, Ibaraki 305 0856, Japan
    Neurosci Lett 413:270-3. 2007
    Protein misfolding cyclic amplification (PMCA) is a highly sensitive technique used to detect minute amounts of scrapie prion protein (PrP(Sc)), a major protein component of the infectious agents associated with prion diseases...
  92. ncbi Transfer of scrapie prion infectivity by cell contact in culture
    Nnennaya Kanu
    Department of Biochemistry and Molecular Biology, University College London, Gower Street, WC1E 6BT, London, United Kingdom
    Curr Biol 12:523-30. 2002
    When a cell is infected with scrapie prions, newly synthesized molecules of the prion protein PrP(C) are expressed at the cell surface and may subsequently be converted to the abnormal form PrP(Sc)...
  93. ncbi A novel method for preclinical detection of PrPSc in blood
    Richard Rubenstein
    Departments of Neurology and Physiology Pharmacology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA
    J Gen Virol 91:1883-92. 2010
    ..disease-associated form of the prion protein (PrP(Sc)) in protease-untreated plasma from preclinical and clinical scrapie sheep, and white-tailed deer with chronic wasting disease, following natural and experimental infection...
  94. 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
    ..Neuro2A cells chronically infected with scrapie prions showed decreased ER-calcium content that correlated with a stronger upregulation of UPR-inducible ..
  95. ncbi Comparative study of the effects of several chemical and physical treatments on the activity of protease resistance and infectivity of scrapie strain 263K
    H L Yao
    National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Ying Xin Rd 100, Beijing 100052
    J Vet Med B Infect Dis Vet Public Health 52:437-43. 2005
    ..of chemical and physical factors on the protease resistant activity in vitro and the infectivity in vivo of scrapie strain 263K, PrPSc from the hamsters infected intracerebrally with scrapie strain 263K were treated with several ..
  96. pmc Molecular and transmission characteristics of primary-passaged ovine scrapie isolates in conventional and ovine PrP transgenic mice
    Alana M Thackray
    Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 OES, United Kingdom
    J Virol 82:11197-207. 2008
    ..Here, we have compared the molecular and transmission characteristics of ovine ARQ/ARQ and VRQ/VRQ scrapie isolates following primary passage in tg338 (VRQ) and tg59 (ARQ) ovine PrP transgenic mice and the conventional ..
  97. pmc Cells expressing anchorless prion protein are resistant to scrapie infection
    Kristin L McNally
    Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA
    J Virol 83:4469-75. 2009
    ..cells expressing GPI-anchored PrP-sen, anchorless PrP-sen, or both forms of PrP-sen were exposed to the mouse scrapie strain 22L. Cells expressing anchored PrP-sen produced PrP-res after exposure to 22L...
  98. pmc Detection of PrPsc in blood from sheep infected with the scrapie and bovine spongiform encephalopathy agents
    L A Terry
    Department of Molecular Pathogenesis and Genetics, Veterinary Laboratories Agency, Woodham Lane, New Haw, Surrey KT15 3NB, United Kingdom
    J Virol 83:12552-8. 2009
    ..In sheep with clinical disease, PrP(sc) was detected in the blood of 55% of scrapie agent-infected animals (n = 80) and 71% of animals with bovine spongiform encephalopathy (n = 7)...
  99. ncbi Dynamics and genetics of PrPSc placental accumulation in sheep
    C Lacroux
    UMR INRA ENVT 1225, Interactions Hôte Agent Pathogène, Ecole Nationale Veterinaire de Toulouse, 23 Chemin des Capelles, 31076 Toulouse, France
    J Gen Virol 88:1056-61. 2007
    Placentae from scrapie-affected ewes are an important source of contamination...
  100. ncbi Complement facilitates early prion pathogenesis
    M A Klein
    Institute of Neuropathology, University of Zurich, Schmelzbergstrasse, Zurich, Switzerland
    Nat Med 7:488-92. 2001
    New-variant Creutzfeldt-Jakob disease and scrapie are typically initiated by extracerebral exposure to the causative agent, and exhibit early prion replication in lymphoid organs...
  101. ncbi PrP(Sc) accumulation in placentas of ewes exposed to natural scrapie: influence of foetal PrP genotype and effect on ewe-to-lamb transmission
    Olivier Andreoletti
    UMR 959 INRA ENVT, Physiopathologie Infectieuse et Parasitaire des Ruminants, Ecole Nationale Veterinaire, 23 Chemin des Capelles, 31076 Toulouse Cedex 3, France
    J Gen Virol 83:2607-16. 2002
    Placentas from scrapie-affected ewes are known to be infectious. Nevertheless, placenta infectivity in such ewes is not systematic...

Research Grants64

  1. Biomimetic Approach to the Fabrication of Red Blood Cell Mimics
    Joseph M DeSimone; Fiscal Year: 2010
    ..and infectious prion proteins the agents associated with variant Creutzfeldt-Jakob disease, mad cow disease, and scrapie. Military uses of blood supplies are also clear...
  2. SYNTHESES AND CELLULAR STUDIES OF NEW PHOTOSENSITIZERS FOR MEDICAL APPLICATIONS
    Kevin M Smith; Fiscal Year: 2013
    ..blood, bone marrow purging, and for inhibition of transmissible spongiform encephalopathies [bovine (BSE), sheep (scrapie) and human forms (Creutzfeld-Jacob disease)]...
  3. Preventing Human Prion Diseases - Inactivation of Prions
    Stanley B Prusiner; Fiscal Year: 2010
    ..we plan to study three strains of prions passaged in mice: RML and 301V, which originated from sheep with scrapie and cattle with BSE, respectively, plus a novel synthetic strain MoSP1, which is the most stable strain reported ..
  4. A Proteomic Approach to Biomarker Discovery in Prion Disease
    Lingjun Li; Fiscal Year: 2009
    ..impact upon human and animal health are Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (BSE), scrapie and chronic wasting disease (CWD)...
  5. Impact of Microparticles on Oral TSE Infections
    Joel A Pedersen; Fiscal Year: 2012
    ..Oral transmission is the primary route of infection for BSE, scrapie and TME and is the suspected route of transmission for vCJD and CWD...
  6. Towards Therapeutics for Neurodegenerative Diseases
    Stanley B Prusiner; Fiscal Year: 2013
    ..The adaption of bioluminescence to the in vivo readout of experimental scrapie and Alzheimer's disease in Tg mice (Tamgtiney et al., 2009a;Watts et al...
  7. Structure and assembly of the fungal prion HET-s
    William N Wan; Fiscal Year: 2013
    ..TSEs include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in deer and elk, and ..
  8. Liposome-siRNA-Peptide Complexes as Therapy to Cure Prion Diseases in Mouse Model
    Mark D Zabel; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Transmissible spongiform encephalopathies (TSEs) include scrapie in sheep;bovine spongiform encephalopathy (BSE) in cattle;chronic wasting disease (CWD) in deer and elk;and Kuru and Creutzfeldt-Jakob ..
  9. Transmissibility of Neurodegenerative Diseases
    DMITRY Y GOLDGABER; Fiscal Year: 2011
    ..to animals were obtained with a notable exception of prion diseases such as Creitzfeldt-Jakob disease in man and scrapie and mad cow disease in animals...
  10. Role of Prion Protein in Manganese Neurotoxicity
    ANUMANTHA GOUNDER KANTHASAMY; Fiscal Year: 2013
    ..protein, iii) to determine whether chronic manganese exposure accelerates the accumulation and aggregation of the scrapie form of prion protein (PrPSc) and causes increased neuronal damage in a mouse model of prion disease, iv) to ..
  11. Characteristics of Prion Entry and Neuroinvasion Following Nasal Cavity Infection
    Anthony E Kincaid; Fiscal Year: 2013
    ..to the horizontal spread of prion disease between animals, such as chronic wasting disease in deer and elk, and scrapie in sheep and goats...
  12. In Vitro Dissection of Genetic Susceptibility to Prion Disease
    George A Carlson; Fiscal Year: 2011
    ..Even the mechanisms by which alternative alleles of Prnp determine scrapie incubation time are unresolved...
  13. Molecular Basis of Iron Imbalance in sCJD Brain and CSF
    Neena Singh; Fiscal Year: 2013
    ..The principal cause of neurotoxicity in this and other prion disorders is accumulation of PrP-scrapie (PrPSc), a [unreadable]-sheet rich isoform of prion protein (PrPC) in the brain parenchyma...
  14. The iron modulatory function of prion protein and prion disorders
    Neena Singh; Fiscal Year: 2013
    ..A change in the conformation of PrPC to an aggregated, PrP-scrapie (PrPSc) form is believed to be the principal cause of neurotoxicity in these disorders...
  15. Neurodegeneration in prion diseases: Therapy and diagnosis
    Claudio Soto; Fiscal Year: 2010
    ..The in vitro results were supported by in vivo data showing that in a murine scrapie model the first alteration consisted on the up-regulation of Grp58 in the brain, which was detected during the ..
  16. Phosphorylation of Prion Protein as a novel mechanism for conversion
    Andrea C LeBlanc; Fiscal Year: 2010
    ..Our preliminary evidence indicates cdk5-independent phosphorylation of PrP in N2A cells and in scrapie- infected mouse brains...
  17. Key molecular mechanisms of extraneural pathogenesis and transmission of TSEs
    Mark D Zabel; Fiscal Year: 2012
    ..These include chronic wating disease (CWD) of deer and elk, scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jacob disease and kuru in humans...
  18. Therapeutic Approaches for Prion Disease
    Thomas M Wisniewski; Fiscal Year: 2013
    ..Mabs will be tested for therapeutic efficacy in tissue culture models of scrapie and human sporadic CJD prion infection and 3) Passive immunization studies using existing Mabs and antibodies ..
  19. Emergence of drug resistance in prion populations
    Roy G Smith; Fiscal Year: 2013
    ..innovation making this investigation possible is the Cell Panel Assay (CPA), which is based on the Standard Scrapie Cell Assay (SSCA), both of which were developed in our laboratories and which allow the rapid discrimination ..
  20. Guanabenz in the treatment of mutant SOD1 ALS mice
    RAYMOND PHILIP ROOS; Fiscal Year: 2013
    ..Guanabenz was previously shown to promote clearance of scrapie prion protein (PrPsc) (a misfolded protein) in tissue-culture cells and also to significantly prolong survival of ..
  21. Function and dysfunction of prion protein in cellular iron metabolism
    Neena Singh; Fiscal Year: 2010
    ..pathogenic agent in all prion disorders comprises of a beta-sheet rich isoform of the prion protein termed PrP-scrapie (PrPSc)...
  22. Role of Brain Ferroxidases in AD and sCJD Pathogenesis
    Neena Singh; Fiscal Year: 2013
    ..from the Singh laboratory indicates a significant reduction of ferroxidase activity in sCJD affected human and scrapie infected mouse brains...
  23. NEUROPEPTIDE REGULATION OF ENTEROPANCREATIC FUNCTION
    Michael W Mulholland; Fiscal Year: 2013
    ..rabbits for experimental use, 6) Providing all animal care and veterinary care, 7) Production of large volumes of scrapie infected hamster and mouse brains for purification, 8) Providing cryopreservation of the various mouse lines...
  24. Structural Characterization of Prion Isoforms in Multiple TSE Diseases
    MICHELE ANN MCGUIRL; Fiscal Year: 2012
    ..CJD) and variant CJD, Gerstmann- Straussler-Scheinker disease, Fatal Familial Insomnia, and kuru (humans), scrapie (sheep), chronic wasting disease (elk, deer), and mad cow disease (cattle)...
  25. Origin and Mechanism of Promiscuous Prion Strains
    Surachai Supattapone; Fiscal Year: 2013
    ..To test this hypothesis, we will simulate the rendering process in the laboratory and study whether sheep scrapie and deer CWD can be converted into promiscuous strains capable of infecting humans or cows...
  26. Molecular basis of cell-specific prion strain propagation
    Charles Weissmann; Fiscal Year: 2010
    ..The aims of this project are to perfect the Scrapie Cell Assay (SCA), which allows the sensitive and rapid quantification of prions in cell culture rather than by ..
  27. Characterization of de novo generation of infectious prions
    Joaquin Castilla; Fiscal Year: 2009
    ..e. Bovine spongiform encephalopathy (BSE) in US cattle and Nor98 (atypical scrapie) in New Zealand sheep, provide evidence that this infrequent spontaneous phenomenon may occur naturally...
  28. Characterization of prion protein conformational changes
    VALERIE D DAGGETT; Fiscal Year: 2010
    ..TSEs, or prion diseases, include Creutzfeldt-Jakob disease, fatal familial insomnia and Kuru in humans, scrapie in sheep, bovine spongiform encephalopathy in cattle, and chronic wasting disease in deer and elk...
  29. Specific amyloid-beta oligomer aptamers
    Karen H Ashe; Fiscal Year: 2010
    ..Srinand Sreevatsan developed DNA aptamers capable of detecting the scrapie isoform of the prion protein in the blood of scrapie-infected sheep, at levels far below the detection threshold ..
  30. Species Susceptibility Assay for Chronic Wasting Disease
    Surachai Supattapone; Fiscal Year: 2005
    ..amplification to measure the potential susceptibility of a range of potential host species to CWD as well as scrapie. Species to be tested include humans, cows, pigs, sheep, goats, chickens, dogs, cats, coyotes, foxes, raccoons, ..
  31. Intercellular transfer of prion in prion disease
    Man Sun Sy; Fiscal Year: 2006
    ..the same pathogenic mechanism based on the conversion of the normal cellular prion (PrP c) into the infectious scrapie prion (prpSc)...
  32. Mechanisms of Prion Misfolding
    Pedro Fernandez Funez; Fiscal Year: 2010
    ..The hallmark pathological event in these maladies is the misfolding, aggregation and brain deposition of scrapie Prion protein (PrPSc), which leads to spongiform degeneration of brain neurons...
  33. CNS DEGENERATION CAUSED BY NOVEL PATHOGENS
    STANLEY PRUSINER; Fiscal Year: 1993
    Prions cause transmissible and genetic neurodegenerative diseases including scrapie and bovine spongiform encephalopathy of animals and Creutzfeldt- Jakob disease and Gerstmann-Straussler-Scheinker syndrome (GSS) of humans...
  34. 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 ..
  35. Germinal Center Function in Prion Disease
    Alan Young; Fiscal Year: 2007
    ..clearly demonstrated a disruption in the differentiation and phenotype of these two B cell subsets in response to scrapie infection...
  36. Structural Investigations of the Prion Protein het-s
    Roland Riek; Fiscal Year: 2006
    ..unreadable] DESCRIPTION (provided by applicant): The "protein-only hypothesis" states that prion diseases such as scrapie in sheep, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease in human are distinct from ..
  37. Biosensor for Rapid Detection of Prion
    Thomas Hazel; Fiscal Year: 2005
    ..prion based on the CANARY biosensor technology developed at MIT and an antibody that specifically recognizes the scrapie form of the prion protein in cattle and humans...
  38. EXPRESSION OF GLYCOLIPID ANCHORED PRIONS IN TRYPANOSOMES
    GEORGE CROSS; Fiscal Year: 2001
    ..propagation involves a self-catalysed conversion of the endogenous cellular protein (PrPC) to the infectious scrapie prion (PrPSc) - cannot readily be tested because of the inability to produce infective PrPSc or native PrPC in ..
  39. CWD: ROLE OF THE LYMPHOID TISSUE PHASE IN PRION DISEASE
    Christina Sigurdson; Fiscal Year: 2004
    ..topical, and important feature of several TSEs, including variant Creutzfeldt-Jakob disease (vCJD) in humans, scrapie in sheep, and chronic wasting disease (CWD) in deer...
  40. Transmissible Spongiform Encephalopathy (Prion) Disease of Deer and Elk
    Laura Solforosi; Fiscal Year: 2007
    ..That aim was to determine the tissue distribution and titers of infectious deer scrapie inoculated into tg mice that have their murine PrP gene ko and replaced by deer PrP controlled by murine PrP ..
  41. Sensitive ImmunoPCR of Blood-Borne Prions
    ELLIOT STEVENS; Fiscal Year: 2009
    ..and lymphoid tissues of affected sheep;(b) Define the presence of PrPd within the blood of clinical end-stage scrapie-affected sheep and (c) Map the appearance of PrPd within the blood of experimentally infected animals throughout ..
  42. CNS DEGENERATION CAUSED BY NOVEL PATHOGENS
    STANLEY PRUSINER; Fiscal Year: 2002
    ..directed toward elucidating the molecular mechanism of conversion of the cellular prion protein) (PrP/c) into the scrapie isoform (PrP/sc) are proposed...
  43. CONVERSION OF A NORMAL PROTEIN TO THE SCRAPIE PROTEIN
    PAUL BENDHEIM; Fiscal Year: 1992
    ..The system we will use involves the scrapie agent amyloid protein (Sp33-37); an abnormally modified, degradation-resistant isoform of a normal cellular ..
  44. Ante-mortem Diagnostics for Prion Infection
    CHAMIKA WANSAPURA; Fiscal Year: 2009
    ..During Phase I, Vegrandis will demonstrate the technology proof-of-concept by performing experiments using scrapie as the model analyte...
  45. CWD--MODEL OF NVCJD AND LYMPHOID PATHOGENESIS IN TSE'S
    Edward Hoover; Fiscal Year: 2003
    ..protein accumulation in lymphoid tissues is an intriguing and likely important feature of several TSE including scrapie in sheep, CWD in deer and nvCJD in humans...
  46. CJD DIAGNOSIS BY IMMUNO-MULTI-SPECTRAL UV FLUORESCENCE
    Richard Rubenstein; Fiscal Year: 2002
    ..measurements of fluorescence from untreated and proteinase K (PK)-treated PrP(Sc), purified from 263K scrapie strain-infected hamster brains and ME7 scrapie strain-infected mouse brains, were performed...
  47. Metals and Protein Structure in Protein-Folding Diseases
    Lisa Miller; Fiscal Year: 2007
    ..are involved in protein misfolding and aggregation in two protein-folding diseases: Alzheimer's disease and scrapie. We hypothesize that elevated concentrations of metal ions (notably Cu, Fe, and Zn) in the brain are involved in ..
  48. PROPERTIES OF CELLULAR PRION PROTEINS
    David Harris; Fiscal Year: 1999
    DESCRIPTION: (adapted from Applicant's Abstract) The scrapie prion protein (PrPsc) is the major component of the infectious particle (prion) responsible for a group of fatal neurodegenerative disorders, including Creutzfeldt-Jakob ..
  49. SCRAPIE AGENT REPLICATION IN AN IN VITRO NEURONAL MODEL
    Richard Rubenstein; Fiscal Year: 1992
    Because of the importance of the nervous system in disease manifestations caused by scrapie, we will pursue detailed investigation of neuronal infection with a variety of scrapie agents...
  50. LATENCY OF SCRAPIE VIRUS: DELAYED DISEASE AND AGING
    JOHN HOTCHIN; Fiscal Year: 1980
    A new form of latent scrapie virus has been found. This causes a delayed form of scrapie in mice 18 months after inoculation of the newborn mouse. The project will characterize this model...
  51. Prion Inactivation in Human Plasma Derived Products
    William Drohan; Fiscal Year: 2003
    ..They will be spiked with scrapie and irradiated at several dosages under varying conditions...
  52. New Animal and Culture Models to rapidly evaluate infectivity of the vCJD Agent
    Laura Manuelidis; Fiscal Year: 2009
    ..We have discovered comparable viruslike particles in cultures with high titers of scrapie infectivity, and thus we suspect such particles can also aid in the diagnosis, prevention and fundamental ..
  53. ACTIVATION OF GENES IN THE AGING BRAIN AND IN SCRAPIE
    Ashley Haase; Fiscal Year: 1991
    We have recently constructed a cDNA library from the brain mRNAs of animals infected with the scrapie agent...
  54. PROTEIN CHEMISTRY OF SCRAPIE AND RELATED DISEASES
    Peter Lansbury; Fiscal Year: 1999
    ..In addition, the possibility for human infection by livestock TSE agent will be studied in detail. Finally, the structure of the protein which comprises the infective agent will be modeled. ..
  55. INVESTIGATIONS OF AMYLOIDOGENESIS
    Sebastian Doniach; Fiscal Year: 2003
    ..is the encephalopathies such as Creuzfeld-Jacob disease in humans, BSC (or 'mad cow disease') in cattle and scrapie in sheep...
  56. MUTATION AND SNP IDENTIFICATION WITHOUT SEQUENCING
    Robert Wagner; Fiscal Year: 1999
    ..Kits will be prepared to identify alleles at three codons of the sheep prion protein gene related to scrapie susceptibility and to precisely identify a collection of key mutations in the p53 tumor suppressor gene...
  57. Experimental Creutzfeldt Jacob Disease
    Laura Manuelidis; Fiscal Year: 2007
    ..We also have successfully passaged the UK BSE agent for comparison, in addition to two reference sheep scrapie agents. Additional human CJD isolates from Japan have also been propagated in mice and cultures...
  58. Amyloid beta Peptide and Apolipoprotein E
    Thomas Wisniewski; Fiscal Year: 2009
    ..These studies will test our central hypothesis that blocking the Aa/apoE interaction can serve as a novel, non-toxic therapeutic target for Alzheimer's disease. ..
  59. Spiroplasma 16S rDNA in TSE Brain Tissues
    Frank Bastian; Fiscal Year: 2006
    ..the transmissible spongiform encephalopathies (TSE), which include Creutzfeldt Jakob disease (CJD) in humans and scrapie in sheep, remains an enigma. In this application we present evidence for the association of Spiroplasma sp...
  60. Immunization Approaches for Alzheimer's Disease
    Thomas Wisniewski; Fiscal Year: 2008
    ..Vaccination is potentially an effective treatment, but is associated with significant toxicity in about 6% of patients. We propose studies to help develop safe, effective vaccines. [unreadable] [unreadable] [unreadable]..
  61. PrP-scrapie transport across intestinal & BBB
    Neena Singh; Fiscal Year: 2007
    ..Despite these concerns, surprisingly little is known about the mechanism(s) by which the infectious prion or PrP-scrapie (PrPsc), a protein of 27-30kDa, is transported from the intestine or peripheral blood to the central nervous ..
  62. Aberrant processing of mutant prion protein in GSS & CJD
    Neena Singh; Fiscal Year: 2005
    ..This study will uncover alternative pathways of neuronal toxicity by mutant PrP besides conversion to PrPSc, and help in developing rational therapeutic strategies. ..
  63. MECHANISM OF CELL DEATH BY PRIONS
    Neena Singh; Fiscal Year: 2004
    ..Abstract): Neuronal death in prion disorders is believed to result from a conformationally transformed, scrapie isoform (PrPSc) of the normal host prion protein (PrPC)...