prion diseases

Summary

Summary: A group of genetic, infectious, or sporadic degenerative human and animal nervous system disorders associated with abnormal PRIONS. These diseases are characterized by conversion of the normal prion protein to an abnormal configuration via a post-translational process. In humans, these conditions generally feature DEMENTIA; ATAXIA; and a fatal outcome. Pathologic features include a spongiform encephalopathy without evidence of inflammation. The older literature occasionally refers to these as unconventional SLOW VIRUS DISEASES. (From Proc Natl Acad Sci USA 1998 Nov 10;95(23):13363-83)

Top Publications

  1. ncbi A general model of prion strains and their pathogenicity
    John Collinge
    MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK
    Science 318:930-6. 2007
  2. 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
  3. ncbi Prions: protein aggregation and infectious diseases
    Adriano Aguzzi
    Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    Physiol Rev 89:1105-52. 2009
  4. pmc Prions
    David W Colby
    Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94143, USA
    Cold Spring Harb Perspect Biol 3:a006833. 2011
  5. pmc Follicular dendritic cell-specific prion protein (PrP) expression alone is sufficient to sustain prion infection in the spleen
    Laura McCulloch
    The Roslin Institute and Royal Dick School of Veterinary Sciences, University of Edinburgh, Midlothian, United Kingdom
    PLoS Pathog 7:e1002402. 2011
  6. ncbi Prion propagation and toxicity in vivo occur in two distinct mechanistic phases
    Malin K Sandberg
    MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
    Nature 470:540-2. 2011
  7. pmc The most infectious prion protein particles
    Jay R Silveira
    Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA
    Nature 437:257-61. 2005
  8. pmc A systems approach to prion disease
    Daehee Hwang
    Institute for Systems Biology, Seattle, WA 98103, USA
    Mol Syst Biol 5:252. 2009
  9. ncbi Mammalian prion biology: one century of evolving concepts
    Adriano Aguzzi
    Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstr 12, CH 8091 Zurich, Switzerland
    Cell 116:313-27. 2004
  10. ncbi Packaging of prions into exosomes is associated with a novel pathway of PrP processing
    L J Vella
    Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria 3010, Australia
    J Pathol 211:582-90. 2007

Detail Information

Publications372 found, 100 shown here

  1. ncbi A general model of prion strains and their pathogenicity
    John Collinge
    MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK
    Science 318:930-6. 2007
    ..Recent advances suggest that prions themselves are not directly neurotoxic, but rather their propagation involves production of toxic species, which may be uncoupled from infectivity...
  2. 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
    ....
  3. ncbi Prions: protein aggregation and infectious diseases
    Adriano Aguzzi
    Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    Physiol Rev 89:1105-52. 2009
    ..PrPC, and therefore, understanding the physiological role of PrPC may help to clarify the mechanism underlying prion diseases. Here we discuss the evolution of the prion concept and how prion-like mechanisms may apply to other protein ..
  4. pmc Prions
    David W Colby
    Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94143, USA
    Cold Spring Harb Perspect Biol 3:a006833. 2011
    ..The prion diseases are characterized by neurodegeneration and lethality...
  5. pmc Follicular dendritic cell-specific prion protein (PrP) expression alone is sufficient to sustain prion infection in the spleen
    Laura McCulloch
    The Roslin Institute and Royal Dick School of Veterinary Sciences, University of Edinburgh, Midlothian, United Kingdom
    PLoS Pathog 7:e1002402. 2011
    b>Prion diseases are characterised by the accumulation of PrP(Sc), an abnormally folded isoform of the cellular prion protein (PrP(C)), in affected tissues...
  6. ncbi Prion propagation and toxicity in vivo occur in two distinct mechanistic phases
    Malin K Sandberg
    MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
    Nature 470:540-2. 2011
    ..Production of neurotoxic species is triggered when prion propagation saturates, leading to a switch from autocatalytic production of infectivity (phase 1) to a toxic (phase 2) pathway...
  7. pmc The most infectious prion protein particles
    Jay R Silveira
    Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA
    Nature 437:257-61. 2005
    ..These results suggest that non-fibrillar particles, with masses equivalent to 14-28 PrP molecules, are the most efficient initiators of TSE disease...
  8. pmc A systems approach to prion disease
    Daehee Hwang
    Institute for Systems Biology, Seattle, WA 98103, USA
    Mol Syst Biol 5:252. 2009
    ..Our systems analysis provides a comprehensive basis for developing models for prion replication and disease, and suggests some possible therapeutic approaches...
  9. ncbi Mammalian prion biology: one century of evolving concepts
    Adriano Aguzzi
    Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstr 12, CH 8091 Zurich, Switzerland
    Cell 116:313-27. 2004
    ..The two decades since Stanley Prusiner's formulation of the protein-only hypothesis have witnessed spectacular advances, and yet some of the most basic questions in prion science have remained unanswered...
  10. ncbi Packaging of prions into exosomes is associated with a novel pathway of PrP processing
    L J Vella
    Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria 3010, Australia
    J Pathol 211:582-90. 2007
    b>Prion diseases are fatal, transmissible neurodegenerative disorders associated with conversion of the host-encoded prion protein (PrP(C)) into an abnormal pathogenic isoform (PrP(Sc))...
  11. 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
    Much evidence supports the hypothesis that the infectious agents of prion diseases are devoid of nucleic acid, and instead are composed of a specific infectious protein...
  12. ncbi Toxic proteins in neurodegenerative disease
    J Paul Taylor
    Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    Science 296:1991-5. 2002
    ..Increased understanding of the cellular mechanisms for disposal of abnormal proteins and of the effects of toxic protein accumulation on neuronal survival may allow the development of rational, effective treatment for these disorders...
  13. pmc Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP
    Simon Mead
    MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
    Hum Mol Genet 21:1897-906. 2012
    b>Prion diseases are fatal neurodegenerative diseases of humans and animals caused by the misfolding and aggregation of prion protein (PrP)...
  14. pmc Ultra-efficient PrP(Sc) amplification highlights potentialities and pitfalls of PMCA technology
    Gian Mario Cosseddu
    Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanita, Rome, Italy
    PLoS Pathog 7:e1002370. 2011
    ..Our findings underline the potential drawback of ultrasensitive in vitro prion replication and warn on cautious interpretation when assessing the spontaneous appearance of prions in vitro...
  15. pmc Detection and characterization of proteinase K-sensitive disease-related prion protein with thermolysin
    Sabrina Cronier
    MRC Prion Unit and Department of Neurodegenerative Disease, University College London Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N3BG, UK
    Biochem J 416:297-305. 2008
    ..Detection of PK-sensitive isoforms of disease-related PrP using thermolysin should be useful for improving diagnostic sensitivity in human prion diseases.
  16. ncbi Physiology of the prion protein
    Rafael Linden
    Instituto de Biofísica da Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
    Physiol Rev 88:673-728. 2008
    b>Prion diseases are transmissible spongiform encephalopathies (TSEs), attributed to conformational conversion of the cellular prion protein (PrP(C)) into an abnormal conformer that accumulates in the brain...
  17. pmc Getting a grip on prions: oligomers, amyloids, and pathological membrane interactions
    Byron Caughey
    Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
    Annu Rev Biochem 78:177-204. 2009
    ....
  18. ncbi Mouse neuroblastoma cells release prion infectivity associated with exosomal vesicles
    Sandrine Alais
    LaboRétro INSERM U758, Unité de Virologie Humaine, Ecole Normale Superieure de Lyon, 69364 Lyon Cedex 07, France
    Biol Cell 100:603-15. 2008
    ..With this aim, we initiated characterization of the prion agent and the pathways by which it can be propagated using the cellular model system neuroblastoma (N2a)...
  19. pmc MicroRNA 146a (miR-146a) is over-expressed during prion disease and modulates the innate immune response and the microglial activation state
    Reuben Saba
    Molecular Pathobiology, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
    PLoS ONE 7:e30832. 2012
    ..Based on our results, we propose a role for miR-146a as a potent modulator of microglial function by regulating the activation state during prion induced neurodegeneration...
  20. pmc Prions on the move
    Charles Weissmann
    Department of Infectology, Scripps Florida, 130 Scripps Way, Jupiter, Florida 33458, USA
    EMBO Rep 12:1109-17. 2011
    ..We propose that prion populations are comprised of a variety of conformers, constituting 'quasi-species', from which the one replicating most efficiently in a particular environment is selected...
  21. pmc Recombinant prion protein induces a new transmissible prion disease in wild-type animals
    Natallia Makarava
    Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA
    Acta Neuropathol 119:177-87. 2010
    ..The length of the clinical duration is more typical of human and large animal prion diseases, than those of rodents...
  22. pmc Molecular cross talk between misfolded proteins in animal models of Alzheimer's and prion diseases
    Rodrigo Morales
    Protein Misfolding Disorders Laboratory, Department of Neurology, Mitchell Center for Alzheimer s Disease and Related Brain Disorders, University of Texas Medical School at Houston, Houston, Texas 77030, USA
    J Neurosci 30:4528-35. 2010
    ..of this study was to analyze the interaction of the protein misfolding processes implicated in Alzheimer's and prion diseases. For this purpose, we inoculated prions in an Alzheimer's transgenic mouse model that develop typical amyloid ..
  23. ncbi The transcellular spread of cytosolic amyloids, prions, and prionoids
    Adriano Aguzzi
    Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH 8091 Zurich, Switzerland
    Neuron 64:783-90. 2009
    ....
  24. pmc Prion protein facilitates uptake of zinc into neuronal cells
    Nicole T Watt
    Faculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK
    Nat Commun 3:1134. 2012
    ..These data suggest that alterations in the cellular prion protein-mediated zinc uptake may contribute to neurodegeneration in prion and other neurodegenerative diseases...
  25. pmc Variably protease-sensitive prionopathy: a new sporadic disease of the prion protein
    Wen Quan Zou
    Department of Pathology, National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH 44106, USA
    Ann Neurol 68:162-72. 2010
    ..The 2 new PSPr forms affect individuals who are either homozygous for methionine (129MM) or heterozygous for methionine/valine (129MV)...
  26. pmc Sustained translational repression by eIF2α-P mediates prion neurodegeneration
    Julie A Moreno
    MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK
    Nature 485:507-11. 2012
    ..Many of these disorders, including Alzheimer's, Parkinson's and prion diseases, are associated with the accumulation of misfolded disease-specific proteins...
  27. ncbi Increased proportions of C1 truncated prion protein protect against cellular M1000 prion infection
    Victoria Lewis
    Department of Pathology, University of Melbourne, Parkville, Victoria, Australia
    J Neuropathol Exp Neurol 68:1125-35. 2009
    ....
  28. pmc Redox control of prion and disease pathogenesis
    Neena Singh
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Antioxid Redox Signal 12:1271-94. 2010
    ..Finally, we discuss possible therapeutic avenues directed at restoring brain metal homeostasis and alleviating metal-induced oxidative stress in prion disorders...
  29. pmc Prion uptake in the gut: identification of the first uptake and replication sites
    Pekka Kujala
    Section of Cell Biology II, Netherlands Cancer Institute, Amsterdam, The Netherlands
    PLoS Pathog 7:e1002449. 2011
    ..Together, these data identify a novel potential M cell-independent mechanism for prion transport, mediated by FAE enterocytes, which acts to initiate conversion and replication upon FDCs and subsequent infection of enteric nerves...
  30. pmc Rapid cell-surface prion protein conversion revealed using a novel cell system
    R Goold
    Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
    Nat Commun 2:281. 2011
    b>Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein...
  31. ncbi The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies
    Michael Beekes
    Robert Koch Institut P24 Transmissible Spongiforme Enzephalopathien, Berlin, Germany
    FEBS J 274:588-605. 2007
    ..It may also help to identify prophylactic or therapeutic approaches that would impede naturally acquired transmissible spongiform encephalopathy infections...
  32. pmc Microglia in the degenerating brain are capable of phagocytosis of beads and of apoptotic cells, but do not efficiently remove PrPSc, even upon LPS stimulation
    Martina M Hughes
    Trinity College Institute of Neuroscience and School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Republic of Ireland
    Glia 58:2017-30. 2010
    ..Furthermore, microglia/macrophages remain IL-1β-negative during phagocytosis of apoptotic cells. The data demonstrate that phagocytic activity and pro-inflammatory microglial phenotype do not necessarily correlate...
  33. ncbi Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease
    C Cunningham
    CNS Inflammation Group, Southampton Neuroscience Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
    Eur J Neurosci 17:2147-55. 2003
    b>Prion diseases are fatal, chronic neurodegenerative diseases of mammals, characterized by amyloid deposition, astrogliosis, microglial activation, tissue vacuolation and neuronal loss...
  34. pmc A molecular switch controls interspecies prion disease transmission in mice
    Christina J Sigurdson
    Department of Pathology and Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
    J Clin Invest 120:2590-9. 2010
    ..These findings point to a triggering role of the local beta2-alpha2 loop structure for prion transmissibility between different species...
  35. ncbi Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent
    M E Bruce
    Institute for Animal Health, BBSRC MRC Neuropathogenesis Unit, Edinburgh, UK
    Nature 389:498-501. 1997
    ..Here we report the interim results of transmissions of sporadic CJD and vCJD to mice. Our data provide strong evidence that the same agent strain is involved in both BSE and vCJD...
  36. 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
    ..This experiment has established the value of using sheep as a model for studying transmission of variant Creutzfeld-Jakob disease by blood products in humans...
  37. pmc Mammalian prions generated from bacterially expressed prion protein in the absence of any mammalian cofactors
    Jae Il Kim
    Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 285:14083-7. 2010
    ....
  38. pmc Continuum of prion protein structures enciphers a multitude of prion isolate-specified phenotypes
    Giuseppe Legname
    Institute for Neurodegenerative Diseases, Department of Neurology, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 103:19105-10. 2006
    ..The biophysical explanation for the unprecedented plasticity of PrP(Sc) remains to be determined...
  39. ncbi The neurotoxicity of prion protein (PrP) peptide 106-126 is independent of the expression level of PrP and is not mediated by abnormal PrP species
    Luana Fioriti
    Dulbecco Telethon Institute, Istituto di Ricerche Farmacologiche Mario Negri, Milan 20157, Italy
    Mol Cell Neurosci 28:165-76. 2005
    ..These results indicate that PrP106-126 interferes with a PrP function that requires only low protein levels, and is not impaired by a pathogenic insertion in the octapeptide region...
  40. pmc Antihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions
    Déborah Tribouillard-Tanvier
    INSERM U613, Brest, France
    PLoS ONE 3:e1981. 2008
    ..Prion-based diseases are incurable transmissible neurodegenerative disorders affecting animals and humans...
  41. ncbi Cellular and sub-cellular pathology of animal prion diseases: relationship between morphological changes, accumulation of abnormal prion protein and clinical disease
    Martin Jeffrey
    Veterinary Laboratories Agency, Lasswade Laboratory, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, EH26 0PZ, UK
    Acta Neuropathol 121:113-34. 2011
    The transmissible spongiform encephalopathies (TSEs) or prion diseases of animals are characterised by CNS spongiform change, gliosis and the accumulation of disease-associated forms of prion protein (PrP(d))...
  42. pmc An overview of human prion diseases
    Muhammad Imran
    Department of Human Genetics and Molecular Biology, University of Health Sciences UHS, Khayaban e Jamia Punjab, Lahore 54600, Pakistan
    Virol J 8:559. 2011
    b>Prion diseases are transmissible, progressive and invariably fatal neurodegenerative conditions associated with misfolding and aggregation of a host-encoded cellular prion protein, PrP(C)...
  43. ncbi Sporadic human prion diseases: molecular insights and diagnosis
    Gianfranco Puoti
    Division of Neurology, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy
    Lancet Neurol 11:618-28. 2012
    Human prion diseases can be sporadic, inherited, or acquired by infection...
  44. pmc MicroRNAs as a molecular basis for mental retardation, Alzheimer's and prion diseases
    Patrick Provost
    CHUL Research Center CHUQ and Faculty of Medicine, Universite Laval, Quebec, QC, Canada
    Brain Res 1338:58-66. 2010
    ....
  45. pmc M cell-depletion blocks oral prion disease pathogenesis
    D S Donaldson
    The Roslin Institute and Royal Dick School of Veterinary Sciences, University of Edinburgh, Edinburgh, UK
    Mucosal Immunol 5:216-25. 2012
    Many prion diseases are orally acquired...
  46. ncbi Oxidative stress and the prion protein in transmissible spongiform encephalopathies
    Ollivier Milhavet
    Institut de Genetique Humaine, CNRS U P R 1142, 141, rue de la Cardonille, 34396 Cedex 5, Montpellier, France
    Brain Res Brain Res Rev 38:328-39. 2002
    ..Subsequently, we will discuss the relationship between the prion protein and the cellular response to oxidative stress, attempting ultimately to link PrP function and neurodegeneration in these disorders...
  47. pmc Prion diseases and their biochemical mechanisms
    Nathan J Cobb
    Department of Physiology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Biochemistry 48:2574-85. 2009
    b>Prion diseases, also known as the transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative disorders that affect humans and animals...
  48. pmc Cellular factors implicated in prion replication
    Karim Abid
    Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA
    FEBS Lett 584:2409-14. 2010
    Prions are the unconventional infectious agents responsible for prion diseases, which are composed mainly by the misfolded prion protein (PrP(Sc)) that replicates by converting the host associated cellular prion protein (PrP(C))...
  49. pmc Cell-free propagation of prion strains
    Joaquin Castilla
    Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, USA
    EMBO J 27:2557-66. 2008
    Prions are the infectious agents responsible for prion diseases, which appear to be composed exclusively by the misfolded prion protein (PrP(Sc))...
  50. pmc Design and construction of diverse mammalian prion strains
    David W Colby
    Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 106:20417-22. 2009
    ....
  51. pmc Mutant PrPSc conformers induced by a synthetic peptide and several prion strains
    Patrick Tremblay
    Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, California 94143, USA
    J Virol 78:2088-99. 2004
    ....
  52. pmc De novo generation of a transmissible spongiform encephalopathy by mouse transgenesis
    Christina J Sigurdson
    Universitatsspital Zurich, Institute of Neuropathology, CH 8091 Zurich, Switzerland
    Proc Natl Acad Sci U S A 106:304-9. 2009
    ..This shows that expression of a subtly altered prion protein, with known 3D structure, efficiently generates a prion disease...
  53. ncbi Lipid rafts: structure, function and role in HIV, Alzheimer's and prion diseases
    Jacques Fantini
    Laboratoire de Biochimie et Physicochimie des Membranes Biologiques, Institut Méditerranéen de Recherche en Nutrition, UMR INRA 1111, Facultédes Sciences de St Jérôme, 13331 Marseille cedex 20, France
    Expert Rev Mol Med 4:1-22. 2002
    ..The possibility of modulating raft homeostasis, using statins and synthetic sphingolipid analogues, offers new approaches for therapeutic interventions in raft-associated diseases...
  54. pmc Detection of protease-resistant cervid prion protein in water from a CWD-endemic area
    T A Nichols
    Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, USA
    Prion 3:171-83. 2009
    ..These data demonstrate detection of very low levels of PrP(CWD) in the environment by sPMCA and suggest persistence and accumulation of prions in the environment that may promote CWD transmission...
  55. pmc Morphological and functional abnormalities in mitochondria associated with synaptic degeneration in prion disease
    Zuzana Siskova
    CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton, UK
    Am J Pathol 177:1411-21. 2010
    ....
  56. pmc Genes contributing to prion pathogenesis
    GULTEKIN TAMGUNEY
    Institute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA
    J Gen Virol 89:1777-88. 2008
    b>Prion diseases are caused by conversion of a normally folded, non-pathogenic isoform of the prion protein (PrP(C)) to a misfolded, pathogenic isoform (PrP(Sc))...
  57. ncbi Eight prion strains have PrP(Sc) molecules with different conformations
    J Safar
    Department of Neurology, University of California, San Francisco 94143 0518, USA
    Nat Med 4:1157-65. 1998
    ....
  58. pmc Highly efficient prion transmission by blood transfusion
    Olivier Andreoletti
    UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Veterinaire de Toulouse, Toulouse, France
    PLoS Pathog 8:e1002782. 2012
    ..These results demonstrate that TSE transmission by blood transfusion can be highly efficient and that this efficiency is more dependent on the viability of transfused cells than the level of infectivity measured by IC inoculation...
  59. pmc Cells release prions in association with exosomes
    Benoit Fevrier
    Centre National de la Recherche Scientifique, Unite Mixte de Recherche 144, Institut Curie, 75005 Paris, France
    Proc Natl Acad Sci U S A 101:9683-8. 2004
    b>Prion diseases are infectious neurodegenerative disorders linked to the accumulation in the central nervous system of the abnormally folded prion protein (PrP) scrapie (PrPsc), which is thought to be the infectious agent...
  60. ncbi Phenotypic heterogeneity in inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and mutant prion protein
    Jonathan D F Wadsworth
    MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery Queen Square, London, UK
    Brain 129:1557-69. 2006
    Inherited prion diseases are caused by PRNP coding mutations and display marked phenotypic heterogeneity within families segregating the same pathogenic mutation...
  61. pmc A new method for the characterization of strain-specific conformational stability of protease-sensitive and protease-resistant PrP
    Laura Pirisinu
    Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanita, Rome, Italy
    PLoS ONE 5:e12723. 2010
    ....
  62. ncbi Enzymatic degradation of prion protein in brain stem from infected cattle and sheep
    Jan P M Langeveld
    Division of Infectious Diseases and Food Chain Quality, Institute for Animal Science and Health, Lelystad, The Netherlands
    J Infect Dis 188:1782-9. 2003
    ..This enzymatic process could lead to the development of a method for the decontamination of medical and laboratory equipment. The ultimate effectiveness of this method of prion inactivation has to be tested in mouse bioassays...
  63. 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
    The central event in the pathogenesis of prion diseases, a group of fatal, transmissible neurodegenerative disorders including Creutzfeldt-Jakob disease (CJD) in humans, is the conversion of the normal or cellular prion protein (PrPC) ..
  64. pmc Protease-sensitive synthetic prions
    David W Colby
    Institute for Neurodegenerative Diseases, University of California, San Francisco, California, United States of America
    PLoS Pathog 6:e1000736. 2010
    ..These novel synthetic prions demonstrate that conformational changes in wild-type PrP can produce mouse prions composed exclusively of sPrP(Sc)...
  65. pmc De novo generation of infectious prions in vitro produces a new disease phenotype
    Marcelo A Barria
    George and Cynthia Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX, USA
    PLoS Pathog 5:e1000421. 2009
    ..The findings also suggest that prion diversity is not restricted to those currently known, and that likely new forms of infectious protein foldings may be produced, resulting in novel disease phenotypes...
  66. ncbi Stromal complement receptor CD21/35 facilitates lymphoid prion colonization and pathogenesis
    Mark D Zabel
    Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    J Immunol 179:6144-52. 2007
    ..Because both PrP(C) and CD21/35 are highly expressed on follicular dendritic cells, CD21/35 appears to be involved in targeting prions to follicular dendritic cells and expediting neuroinvasion following peripheral exposure to prions...
  67. ncbi Endoplasmic reticulum stress features are prominent in Alzheimer disease but not in prion diseases in vivo
    Ursula Unterberger
    Institute of Neurology, Medical University of Vienna, Austria
    J Neuropathol Exp Neurol 65:348-57. 2006
    b>Prion diseases and Alzheimer disease (AD) share a variety of clinical and neuropathologic features (e.g...
  68. ncbi Prediction of amyloid fibril-forming proteins
    Y Kallberg
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Medical Nobel Institute, Karolinska Institutet, S-171 77 Stockholm, Sweden
    J Biol Chem 276:12945-50. 2001
    ..Likewise, when Abeta residues 14-23 are removed or changed to a nondiscordant sequence, fibrils are no longer formed. We propose that alpha-helix/beta-strand-discordant stretches are associated with amyloid fibril formation...
  69. ncbi Association of an 11-12 kDa protease-resistant prion protein fragment with subtypes of dura graft-associated Creutzfeldt-Jakob disease and other prion diseases
    Katsuya Satoh
    Department of Neurological Science, Tohoku University Graduate School of Medicine, 2 1 Seiryo machi, Sendai 980 8575, Japan
    J Gen Virol 84:2885-93. 2003
    ..The disease type-specific association of fPrP11-12 was also observed in subjects with other prion diseases. An fPrP11-12-like C-terminal PrP fragment was detected in brain lysates from patients associated with fPrP11-..
  70. pmc Infectious prions in pre-clinical deer and transmission of chronic wasting disease solely by environmental exposure
    Candace K Mathiason
    Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America
    PLoS ONE 4:e5916. 2009
    Key to understanding the epidemiology and pathogenesis of prion diseases, including chronic wasting disease (CWD) of cervids, is determining the mode of transmission from one individual to another...
  71. 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
    ..Finally, we observed the release of PrPC/PrPSc via exocytotic pathways, i.e. via exosomes and as an opaque electron-dense mass which may represent a mechanism of intercellular spreading of infectious prions...
  72. ncbi The neurodegeneration sequence in prion diseases: evidence from functional, morphological and ultrastructural studies of the GABAergic system
    Essia Bouzamondo-Bernstein
    Institute for Neurodegenerative Diseases, and Department of Pathology, University of California San Francisco, San Francisco, California, USA
    J Neuropathol Exp Neurol 63:882-99. 2004
    ..Loss of the GABAergic system of neurons has been reported to be the first detectable neuropathological change in prion diseases, which features the accumulation of an aberrant isoform of the prion protein (PrP(Sc))...
  73. pmc Proteasomal dysfunction and endoplasmic reticulum stress enhance trafficking of prion protein aggregates through the secretory pathway and increase accumulation of pathologic prion protein
    Max Nunziante
    Institute of Virology, Prion Research Group, Technische Universitat Munchen, 81675 Munich, Germany
    J Biol Chem 286:33942-53. 2011
    ..PrP(c)) underlies formation of PrP(Sc), which is closely associated with pathogenesis and transmission of prion diseases. The precise conformational prerequisites and the cellular environment necessary for this post-translational ..
  74. pmc A new mechanism for transmissible prion diseases
    Natallia Makarava
    Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, Maryland 21201, USA
    J Neurosci 32:7345-55. 2012
    ..The current work demonstrates that a new mechanism responsible for prion diseases different from the PrP(Sc)-templated or spontaneous conversion of PrP(C) into PrP(Sc) exists...
  75. pmc Post-natal knockout of prion protein alters hippocampal CA1 properties, but does not result in neurodegeneration
    G R Mallucci
    MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK
    EMBO J 21:202-10. 2002
    ..Furthermore, they show that acute depletion of PrP does not affect neuronal survival in this model, ruling out loss of PrP function as a pathogenic mechanism in prion disease and validating therapeutic approaches targeting PrP...
  76. ncbi A brain aggregate model gives new insights into the pathobiology and treatment of prion diseases
    Krystyna Bajsarowicz
    Department of Pathology, University of California, San Francisco, USA
    J Neuropathol Exp Neurol 71:449-66. 2012
    ..We conclude that the decrease was dominated by the ability of Qa to decrease the formation of PrP. Therefore, BrnAggs provide an efficient in vitro tool for screening drug therapies and studying the complex biology of prions...
  77. pmc Prion-induced activation of cholesterogenic gene expression by Srebp2 in neuronal cells
    Christian Bach
    Institute of Virology, Technische Universitat Munchen, Trogerstrasse 30, 81675 Munich, Germany
    J Biol Chem 284:31260-9. 2009
    b>Prion diseases are neurodegenerative diseases associated with the accumulation of a pathogenic isoform of the host-encoded prion protein. The cellular responses to prion infection are not well defined...
  78. ncbi Prion stability and infectivity in the environment
    Richard C Wiggins
    National Health and Environmental Effects Research Laboratory, US EPA Office of Research and Development, MD B305 02, Research Triangle Park, NC 27711, USA
    Neurochem Res 34:158-68. 2009
    ..Since certain of the prion diseases have a history of epidemics in economically important animal species and have the potential to transmit to ..
  79. pmc Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents
    Yervand Eduard Karapetyan
    Department of Infectious Diseases, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA
    Proc Natl Acad Sci U S A 110:7044-9. 2013
    b>Prion diseases such as Creutzfeldt-Jakob disease (CJD) are incurable and rapidly fatal neurodegenerative diseases...
  80. pmc Crucial role for prion protein membrane anchoring in the neuroinvasion and neural spread of prion infection
    Mikael Klingeborn
    Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA
    J Virol 85:1484-94. 2011
    In nature prion diseases are usually transmitted by extracerebral prion infection, but clinical disease results only after invasion of the central nervous system (CNS)...
  81. ncbi The genetics of prion diseases
    James A Mastrianni
    Department of Neurology, The University of Chicago, Chicago, Illinois 60637, USA
    Genet Med 12:187-95. 2010
    b>Prion diseases are a rare group of fatal neurodegenerative disorders of humans and animals that manifest primarily as progressive dementia and ataxia...
  82. ncbi Facilitated cross-species transmission of prions in extraneural tissue
    Vincent Beringue
    Institut National de la Recherche Agronomique UR892, Virologie Immunologie Moléculaires, Jouy en Josas, France
    Science 335:472-5. 2012
    ..Thus, prion cross-species transmission efficacy can exhibit a marked tissue dependence...
  83. pmc Dissociation of infectivity from seeding ability in prions with alternate docking mechanism
    Michael B Miller
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire, United States of America
    PLoS Pathog 7:e1002128. 2011
    ..These results suggest that the propagation of PrP(Sc) molecules may not depend on a single stereotypic mechanism, but that normal PrP(C)/PrP(Sc) interaction through polybasic domains may be required to generate prion infectivity...
  84. pmc Orally administered prion protein is incorporated by m cells and spreads into lymphoid tissues with macrophages in prion protein knockout mice
    Ikuro Takakura
    Cellular Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
    Am J Pathol 179:1301-9. 2011
    ....
  85. ncbi Common structural traits across pathogenic mutants of the human prion protein and their implications for familial prion diseases
    Giulia Rossetti
    Statistical and Biological Physics Sector, Scuola Internazionale Superiore di Studi Avanzati SISSA, via Bonomea 265, I 34136 Trieste, Italy
    J Mol Biol 411:700-12. 2011
    Human (Hu) familial prion diseases are associated with about 40 point mutations of the gene coding for the prion protein (PrP). Most of the variants associated with these mutations are located in the globular domain of the protein...
  86. pmc Discovery of 2-aminothiazoles as potent antiprion compounds
    Sina Ghaemmaghami
    Institute for Neurodegenerative Diseases, San Francisco, CA 94143 0518, USA
    J Virol 84:3408-12. 2010
    b>Prion diseases are fatal, untreatable neurodegenerative diseases caused by the accumulation of the misfolded, infectious isoform of the prion protein (PrP), termed PrP(Sc)...
  87. ncbi Synthetic mammalian prions
    Giuseppe Legname
    Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
    Science 305:673-6. 2004
    ..Neuropathological findings suggest that a novel prion strain was created. Our results provide compelling evidence that prions are infectious proteins...
  88. pmc Darwinian evolution of prions in cell culture
    Jiali Li
    Department of Infectology, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA
    Science 327:869-72. 2010
    ..Prions, albeit devoid of a nucleic acid genome, are thus subject to mutation and selective amplification...
  89. pmc Genesis of mammalian prions: from non-infectious amyloid fibrils to a transmissible prion disease
    Natallia Makarava
    Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, Maryland, United States of America
    PLoS Pathog 7:e1002419. 2011
    ..The current work illustrates that transmissible prion diseases can be induced by PrP structures different from that of authentic PrP(Sc) and suggests that a new mechanism ..
  90. ncbi Microglia and the pathogenesis of spongiform encephalopathies
    P Rezaie
    Department of Neuropathology, Institute of Psychiatry, King's College London, DeCrespigny Park, SE5 8AF, London, UK
    Brain Res Brain Res Rev 35:55-72. 2001
    ..The prion diseases, also known as spongiform encephalopathies, are fatal neurodegenerative disorders with sporadic, genetic or ..
  91. pmc Biochemical properties of highly neuroinvasive prion strains
    Cyrus Bett
    Department of Pathology, University of California, San Diego, La Jolla, California, USA
    PLoS Pathog 8:e1002522. 2012
    ....
  92. ncbi The role of lipid rafts in prion protein biology
    Victoria Lewis
    Department of Pathology, University of Melbourne, Victoria 3010, Australia
    Front Biosci (Landmark Ed) 16:151-68. 2011
    ..the misfolded isoform PrP(Sc )is the central pathogenic event in the uniquely transmissible neurodegenerative prion diseases. As both PrP(C) and PrP(Sc) are associated with membranes, the nature of the membrane microenvironment may ..
  93. ncbi A highly sensitive immunoassay for the detection of prion-infected material in whole human blood without the use of proteinase K
    M Howard Tattum
    MRC Prion Unit and the Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK
    Transfusion 50:2619-27. 2010
    ....
  94. ncbi Prion protein is necessary for normal synaptic function
    J Collinge
    Department of Biochemistry and Molecular Genetics, St Mary s Hospital Medical School, Imperial College, London, UK
    Nature 370:295-7. 1994
    The prion diseases are neurodegenerative conditions, transmissible by inoculation, and in some cases inherited as an autosomal dominant disorder...
  95. pmc Prion protein misfolding and disease
    Roger A Moore
    Rocky Mountain Laboratories, Laboratory of Persistent Viral Diseases, NIAID, NIH, 903 S 4th Street, Hamilton, MT 59840, United States
    Curr Opin Struct Biol 19:14-22. 2009
    Transmissible spongiform encephalopathies (TSEs or prion diseases) are a rare group of invariably fatal neurodegenerative disorders that affect humans and other mammals...
  96. pmc Prion disease susceptibility is affected by beta-structure folding propensity and local side-chain interactions in PrP
    M Qasim Khan
    Campbell Family Institute for Cancer Research, Department of Biochemistry, University of Toronto, Toronto Medical Discovery Tower 4 307, 101 College Street, Toronto, ON, Canada M5G 1L7
    Proc Natl Acad Sci U S A 107:19808-13. 2010
    b>Prion diseases occur when the normally α-helical prion protein (PrP) converts to a pathological β-structured state with prion infectivity (PrP(Sc)). Exposure to PrP(Sc) from other mammals can catalyze this conversion...
  97. ncbi Variant Creutzfeldt-Jakob disease
    J W Ironside
    National Creutzfeldt Jakob Disease Surveillance Unit, Division of Pathology, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK
    Haemophilia 16:175-80. 2010
    ..Continued surveillance is required to investigate the prevalence of secondary variant CJD infection in other patients with bleeding disorders who have been treated with UK-sourced pooled plasma products...
  98. 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)...
  99. 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
    ..Studies of prion diseases may advance investigations of other neurodegenerative disorders and of how neurons differentiate, function for ..
  100. pmc Generating a prion with bacterially expressed recombinant prion protein
    Fei Wang
    Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, OH 43210, USA
    Science 327:1132-5. 2010
    ..Thus, as postulated by the prion hypothesis, the infectivity in mammalian prion disease results from an altered conformation of PrP...
  101. pmc All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD
    Sandra McCutcheon
    The Roslin Institute and Royal Dick School of Veterinary Studies, University of Edinburgh, Roslin, Edinburgh, United Kingdom
    PLoS ONE 6:e23169. 2011
    ..These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion...

Research Grants75

  1. SYNTHESES AND CELLULAR STUDIES OF NEW PHOTOSENSITIZERS FOR MEDICAL APPLICATIONS
    Kevin M Smith; Fiscal Year: 2013
    ..The full potential can be realized only when new drugs with higher cellular selectivity and specificity are discovered, their mechanisms of biological action investigated, and their efficacy evaluated relative to existing modalities. ..
  2. WHOLE SLIDE IMAGING SYSTEM FOR TRANSLATIONAL NEUROSCIENCE
    Jin Moo Lee; Fiscal Year: 2010
    ..multiple sclerosis, ischemic stroke, intracerebral hemorrhage, CNS infections, brain tumors, neurotrauma, prion diseases, and peripheral nerve injury...
  3. NOVEL THERAPEUTICS FOR PRION DISEASES
    Stanley B Prusiner; Fiscal Year: 2013
    ..The prion diseases are invariably fatal and no effective treatment exists...
  4. MALDI-TOF/TOF MS TO SUPPORT BIOMEDICAL RESEARCH
    Catherine E Costello; Fiscal Year: 2012
    ..topics include Cardiovascular Disease, Alzheimer Disease, familial and sporadic systemic amyloid diseases, prion diseases, Cancer, Huntington Disease, Lyme and Rheumatoid Arthritis, Sickle Cell Disease, Traumatic Brain Injury, ..
  5. A Proteomic Approach to Biomarker Discovery in Prion Disease
    Lingjun Li; Fiscal Year: 2009
    ..biomarkers will provide a basis for the development of an ante-mortem antibody-based screening test for prion diseases in suspected animals...
  6. Impact of Microparticles on Oral TSE Infections
    Joel A Pedersen; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Prion diseases are inevitably fatal, transmissible disorders inducing a progressive neurologic dysfunction after a prolonged incubation period...
  7. Structure and assembly of the fungal prion HET-s
    William N Wan; Fiscal Year: 2013
    ..Preliminary results demonstrate the amenability of HET-s(218-289) to structure determination and biophysical characterization as well as its similarities to and subsequent extensibility in the study of pathological prions. ..
  8. Liposome-siRNA-Peptide Complexes as Therapy to Cure Prion Diseases in Mouse Model
    Mark D Zabel; Fiscal Year: 2013
    ..Recent advances toward an effective therapy for prion diseases employ RNAi to suppress expression of a normal host protein, PrPC, in neurons and subsequent prion ..
  9. The Role of Toxic Ion Channels in ALS Pathogenesis
    Michael J Allen; Fiscal Year: 2013
    ..With successful funding we are convinced that continuation of our work will lead to the development of new antibody-based diagnostics, as well as effective new therapeutic treatments for ALS. ..
  10. Acquisition of a Leica TCS SP5 Confocal Microscope For A Multi-User Facility
    Patricia A Conrad; Fiscal Year: 2013
    ..goal of developing better strategies to alleviate resistance), and examining transport and neurotoxicity in Prion Diseases (with the goal of determining pathogenesis.)...
  11. Investigation of the Establishment of the Prion State
    Irina L Derkatch; Fiscal Year: 2010
    ..is expected to facilitate the development of new strategies for preventing the onset and transmission of prion diseases. The long-term goal of PI's research is to understand the biogenesis and biological role of prions, ..
  12. Role of Prion Protein in Manganese Neurotoxicity
    ANUMANTHA GOUNDER KANTHASAMY; Fiscal Year: 2013
    ..Therefore, dysregulation of metal homeostasis has been suggested to play a role in the pathogenesis of prion diseases. Recent observations of elevated manganese (Mn) levels in the brain and blood of humans and animals afflicted ..
  13. Transmissibility of Neurodegenerative Diseases
    DMITRY Y GOLDGABER; Fiscal Year: 2011
    ..no experimental proof of transmission from human cases 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...
  14. Trekking with the Ribognome: Single Molecule Microscopy of Intracellular miRNPs
    Nils G Walter; Fiscal Year: 2010
    ..protein assembly, particularly that occurring during protein misfolding diseases such as Alzheimer's and prion diseases, be detected by our novel "molecular Christmas tree" probe concept? What are the lower limits for DNA repeat ..
  15. Fluorescence Fluctuation Spectroscopy for von Willebrand Factor Multimer Analysis
    Michael J Levene; Fiscal Year: 2010
    ..will have broad applicability to the measurement of oligomerization, including the study of amyloid and prion diseases. VWF is a blood protein that is critical for proper clotting and exists in multimers composed of between 2 and ..
  16. Pathogenesis, Transmission and Detection of Zoonotic Prion Diseases (P01)
    Claudio Soto; Fiscal Year: 2012
    ..The findings generated in this Program will have undoubtedly contribute to understand the pathogenesis, route of propagation and early detection of these two worrisome zoonotic prion diseases.
  17. Characteristics of Prion Entry and Neuroinvasion Following Nasal Cavity Infection
    Anthony E Kincaid; Fiscal Year: 2013
    ..This route of inoculation is likely to be relevant to the natural spread of prion diseases because a study published this year demonstrated that sheep can be infected with scrapie via intranasal ..
  18. Development of a Biochemical Diagnosis for Creutzfeldt-Jakob disease
    Claudio Soto; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Human prion diseases are infectious and invariably fatal forms of neurodegenerative diseases, including sporadic Creutzfeldt-Jakob disease (sCJD), the most common form, and variant CJD (vCJD) which is ..
  19. Molecular Mechanisms of Prion and Amyloid Propagation
    Christopher P Jaroniec; Fiscal Year: 2013
    ..In addition, we will use hydrogen/deuterium exchange solution NMR methods, atomic force microscopy and tilted-beam transmission electron microscopy. ..
  20. Feed Safety and BSE/Ruminant Feed Ban Support Project (U18)
    CLAUDIA G COLES; Fiscal Year: 2013
    ..WSDA describes how even very very low probability events are significant for prion diseases due to pre-clinical infectivity, long incubation periods and 100% mortality in animals and humans...
  21. Structural basis of species-specific infectivities of two prion strains
    Peter M Tessier; Fiscal Year: 2010
    ..2-sheet rich conformation, but a suite of related aggregated conformers that are responsible for different prion diseases. Naturally occurring prions in yeast also display very similar behavior...
  22. Elucidating the Relations of Heat Shock Factors, Molecular Chaperones and Prions
    Liming Li; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: Prion diseases are a group of infectious neurodegenerative diseases also known as transmissible spongiform encephalopathies...
  23. Phosphorylation of Prion Protein as a novel mechanism for conversion
    Andrea C LeBlanc; Fiscal Year: 2010
    ..A fragment of the phosphorylated prion protein becomes resistant to proteinase K as it often does in prion diseases. Furthermore, electron microscopy shows the formation of fibrillar and globular aggregate structures in ..
  24. Mechanisms of prion transport
    Richard A Bessen; Fiscal Year: 2013
    b>Prion diseases are fatal neurodegenerative diseases of humans and animals. Dissemination in the nervous system occurs by prion agent movement along nerve fibers and transynaptic spread between neurons...
  25. Key molecular mechanisms of extraneural pathogenesis and transmission of TSEs
    Mark D Zabel; Fiscal Year: 2012
    b>Prion diseases are invariably fatal infectious diseases affecting a wide range of animals...
  26. Therapeutic Approaches for Prion Disease
    Thomas M Wisniewski; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prion diseases are infectious, conformational neurodegenerative disorders characterized by the structural modification of the prion protein, PrPC, into a pathological conformer, PrPSc...
  27. Pathogenetic Mechanisms of Prion Disease
    Pierluigi Gambetti; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The Program Project focuses on three major aspects of human prion diseases: 1) structure of human PrPSc, 2) non-invasive, accurate diagnosis;3) prion diversity and phenotypic determination, and ..
  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 ..
  29. Absorption, Metabolism and Biodistribution of Prions after Oral Ingestion
    Claudio Soto; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prion diseases are a group of fatal neurodegenerative disorders affecting animals and humans...
  30. Molecular Aspects of Copper Binding to the Prion Protein
    Glenn L Millhauser; Fiscal Year: 2013
    ..These proteins are essential for neuron health and understanding their behavior will lead to new strategies for treating neurodegenerative diseases, such as Alzheimer's, and treating brain trauma. ..
  31. Emergence of drug resistance in prion populations
    Roy G Smith; Fiscal Year: 2013
    ..The finding that prions can acquire drug resistance impacts on the strategies envisaged for therapeutic approaches to prion disease. ..
  32. A new genetic approach for studying prions and other pathogenic protein aggregate
    Ann Hochschild; Fiscal Year: 2012
    ..abstract_text> ..
  33. A new genetic approach for studying prions and other pathogenic protein aggregate
    Ann Hochschild; Fiscal Year: 2011
    ..abstract_text> ..
  34. Engineering chaperones for extracellular amyloids
    Diego E Rincon-Limas; Fiscal Year: 2013
    ..are expected to have a positive impact because they will lead to the application of secHsp70 in other cerebral amyloidosis, such as prion diseases, as well as in disorders with systemic distribution of amyloids, such as Type 2 diabetes.
  35. Allele-Specific RNAi to treat Genetic Prion Disease - Resubmission 01
    James A Mastrianni; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prion diseases are fatal neurodegenerative diseases that result from the accumulation of a misfolded isoform of the prion protein (PrPSc)...
  36. Function and dysfunction of prion protein in cellular iron metabolism
    Neena Singh; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: Prion diseases are fatal neurodegenerative disorders for which there is currently no treatment...
  37. Mechanisms of prion aggregation and species barriers
    Christina Sigurdson; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prion diseases are infectious and fatal neurodegenerative disorders with no available treatment...
  38. Heat Shock Directed Drug Discovery For The Treatment Of Gliomas
    Sandro Santagata; Fiscal Year: 2012
    ..Of additional relevance, some of these HSR modulating drugs may have application in classic protein folding CNS disorders such as neurodegenerative and prion diseases.
  39. PMCA Detection of CWD Infection in Cervid and Non-Cervid Species
    EDWARD ARTHUR HOOVER; Fiscal Year: 2013
    ..The increasing parallels in the pathogenesis between prion diseases and human neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, add relevance ..
  40. High-Throughput Nanoscale Approaches to Studying and Inhibiting Amyloid Toxicity
    Timothy Lu; Fiscal Year: 2011
    ..by the applicant) Abstract: Amyloids play an integral role in a broad range of human illnesses including prion diseases, neurodegenerative conditions such as Alzheimer's and Parkinson's diseases, systemic amyloidoses, ..
  41. Cyclic Amplification of Prion Protein Misfolding
    Claudio Soto; Fiscal Year: 2013
    ..b>Prion diseases are a group of infectious neurodegenerative disorders associated with the cerebral accumulation of misfolded ..
  42. MURINE TRANSGENIC MODELS OF PRION DISEASES
    David A Harris; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The overall goal of this project is to investigate the pathogenesis of prion diseases using transgenic mouse models...
  43. Structural Characterization of Prion Isoforms in Multiple TSE Diseases
    MICHELE ANN MCGUIRL; Fiscal Year: 2012
    ..in its aggregated isoforms, and to elucidate the relationship between isoform structure and different types of prion diseases. Prion protein is the causative agent of many fatal neurodegenerative diseases of mammals...
  44. Investigation of the yeast prion factor [PSI+]
    Susan W Liebman; Fiscal Year: 2012
    ..diseases including Alzheimer's, Huntington's and Parkinson's, as well as with the infectious prion diseases e.g. Mad Cow, Chronic Wasting in deer and Creutzfeldt-Jacob in humans...
  45. UPTAKE, TRANSPORT, AND SPREAD OF PRIONS
    David A Harris; Fiscal Year: 2010
    b>Prion diseases are fatal neurodegenerative disorders of humans and animals...
  46. Characterization of chaperone-prion specificity in Saccharomyces cerevisiae
    JUSTIN KEITH HINES; Fiscal Year: 2010
    ..may lead to the ability to manipulate chaperone proteins in the pursuit of treatments for amyloid and prion diseases. Relevance: Neurodegenerative diseases such as Parkinson's and Alzheimer's are of a growing concern ..
  47. DEGENERATIVE AND DEMENTING DISEASES OF AGING
    Stanley B Prusiner; Fiscal Year: 2013
    ..projects and four-cores, we propose to continue our studies focused on neurodegeneration caused by human prion diseases, the most common of which is sporadic (s) CJD...
  48. Multidimensional Femtosecond Correlation Spectroscopic Probes of Biomolecules
    Shaul Mukamel; Fiscal Year: 2013
    ..Surface specific technique will be applied for probing the toxicity of fibrils on membranes. Simulation techniques for probing the binding, fluctuations, and motions of biomolecular complexes will be developed. ..
  49. Predicting progression of human prion disease
    Michael D Geschwind; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Human prion diseases, such as Jakob-Creutzfeldt disease (CJD) are devastating neurodegenerative diseases that currently are untreatable...
  50. Genome-wide screening for effectors of toxic prion protein-induced neuronal death
    Corinne Ida Lasmezas; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prion diseases are fatal protein misfolding neurodegenerative diseases (PMNDs) like Alzheimer, Parkinson, Huntington's Diseases or Amyotrophic Lateral Sclerosis...
  51. Molecular determinants of lamin a accumulation in human aging and disease
    Agnieszka Kalinowski; Fiscal Year: 2012
    ..that result from destructive protein-membrane interactions, such as Alzheimer's disease, tauopathies and prion diseases. In this project, we will determine whether the strong interaction between (delta)50 lamin A and the inner ..
  52. Mechanism of GroEL-assisted Protein Folding
    Lingling Chen; Fiscal Year: 2010
    ..to a better understanding of folding-related human diseases, such as Cystic Fibrosis, Alzheimer's, Prion diseases and cataracts, at the molecular level, and could lead to the design of novel therapeutic approaches...
  53. Mimicry of Amyloid Oligomers
    James S Nowick; Fiscal Year: 2013
    ..neurodegenerative disorders, including Alzheimer's disease, Huntington's disease, and the prion diseases. Although amyloid fibrils have long been viewed as the hallmark of Alzheimer's and other ..
  54. Therapeutic Targeting of Abnormal Conformation in Neurodegenerative Disease
    Thomas M Wisniewski; Fiscal Year: 2013
    ..conformational disorders, which include diffuse Lewy body disease (DLBD), Parkinson's disease (PD), prion diseases, and frontotemporal lobar degeneration (FTLD). The most toxic conformers are the oligomeric forms...
  55. High Throughput Screening for compounds reducing cell surface prion protein
    Corinne Ida Lasmezas; Fiscal Year: 2013
    ..b>Prion diseases are transmisible neurodegenerative diseases caused by misfolding of PrP...
  56. Self-Propagating Mechanism of Prion Diseases
    Ilia V Baskakov; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prion diseases are a group of fatal age-dependent neurodegenerative diseases that can arise spontaneously or be inherited, but can also be infectious...
  57. CWD: A Model of Prion Transmission via Saliva and Urine
    NICHOLAS JAMES HALEY; Fiscal Year: 2013
    ..In addition, the mechanisms of pathogenesis and transmission of prion diseases are not clearly defined...
  58. ION CHANNEL MODULATION BY THE PRION PROTEIN: A NOVEL TOXIC MECHANISM
    David A Harris; Fiscal Year: 2013
    ..point mutations in the central region of PrP have a similar effect, suggesting that some familial prion diseases are due to excitotoxic activation of ion channels...
  59. A Prion Reveals Complex Traits and Phenotypic Diversity
    HEATHER L TRUE-KROB; Fiscal Year: 2013
    ..in many neurodegenerative disorders including Parkinson's, Alzheimer's, Huntington's, and prion diseases. We are investigating how a group of proteins adopt a specific type of "misfolded" state (prion conformation) ..
  60. Identifying the Role of PrPSc Distribution &Other Proteins in Prion Pathogenesis
    David B Berry; Fiscal Year: 2013
    ..b>Prion diseases encompass a range of genetic, spontaneous, and transmitted neuropathologies that affect humans and a number of ..
  61. Pathogenicity of prion protein aggregates from uninfected cells and brains
    Wen Quan Zou; Fiscal Year: 2013
    ..the major component of prions that cause a group of fatal transmissible spongiform encephalopathies or prion diseases in animals and humans...
  62. Harnessing novel cell-penetrating antibodies for neuronal correction
    Anne Messer; Fiscal Year: 2012
    ..human neurodegenerative disorders, including Huntington's, Parkinson's, Alzheimer's, and prion diseases. However, the practical application of intrabodies is currently hampered by a lack of robust gene or protein ..
  63. Characterization of de novo generation of infectious prions
    Joaquin Castilla; Fiscal Year: 2009
    ..The occurrence of spontaneous cases of prion diseases in humans (sporadic CJD) and in other species, i.e...
  64. Intercellular transfer of prion in prion disease
    Man Sun Sy; Fiscal Year: 2006
    unreadable] DESCRIPTION (provided by applicant): Transmissible spongiform encephalopathies (TSE) or prion diseases are a group of fatal neuro-degenerative disorders that affect both humans and animals...
  65. CEREBROVASCULAR AMYLOIDOSIS
    Peter Gorevic; Fiscal Year: 1999
    ..for the central nervous system that may manifest prominent cerebrovascular amyloidosis include the prion diseases, certain hereditary stroke-like syndromes due to cystatin C or Alzheimer's disease (AD) amyloid beta protein (..
  66. Biochemical Detection of Prions in Blood
    Joaquin Castilla; Fiscal Year: 2005
    ..Transmissible spongiform encephalopathies, also called prion diseases, are a group of fatal infectious neurodegenerative disorders affecting humans and animals...
  67. CNS DEGENERATION CAUSED BY NOVEL PATHOGENS
    STANLEY PRUSINER; Fiscal Year: 1993
    ..Molecular genetic studies in mice and humans have shown that susceptibility to prion diseases - experimental scrapie in mice and GSS in humans - is genetically linked to mutations in the open reading ..
  68. 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 ..
  69. Germinal Center Function in Prion Disease
    Alan Young; Fiscal Year: 2007
    ..Blood is known to be infectious in prion diseases. To address this concern, individuals at risk for harboring human prion disease are now excluded from donating ..
  70. TRANSMISSIBLE AND GENETIC NEURODENGENERATIVE DISEASES
    STANLEY PRUSINER; Fiscal Year: 1999
    b>Prion diseases are neurodegenerative disorders of humans and animals. These diseases can present as genetic, infectious or sporadic illnesses and are often transmissible to experimental animals...
  71. MOLECULAR DETERMINANTS OF HUMAN PRION DISEASES
    James Mastrianni; Fiscal Year: 2000
    ..my proposed investigations are to define the mechanism by which prions are generated de-novo in the inherited prion diseases and to develop as a physician-scientist...
  72. 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. ..
  73. Interaction of Prions with Dendritic Cells
    Michael Green; Fiscal Year: 2004
    ..outbreak of chronic wasting disease among deer and elk in the United States have brought the issue of prion diseases into the spotlight...
  74. Transmission of Prions Within and Between Species
    Robert Harrington; Fiscal Year: 2006
    ..Harrington with a well rounded scientific background and allow specific research training pertinent to his area of research interest. [unreadable] [unreadable]..
  75. CWD: ROLE OF THE LYMPHOID TISSUE PHASE IN PRION DISEASE
    Christina Sigurdson; Fiscal Year: 2004
    ..The results of these studies will contribute to understanding PrP trafficking in the lymphoid system and could provide a basis for development of blood-based diagnostic assays and intervention strategies. ..