prions

Summary

Summary: Small proteinaceous infectious particles which resist inactivation by procedures that modify NUCLEIC ACIDS and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PRPSC PROTEINS) and the cellular isoform PrPC (PRPC PROTEINS). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include CREUTZFELDT-JAKOB SYNDROME; GERSTMANN-STRAUSSLER SYNDROME; and INSOMNIA, FATAL FAMILIAL.

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. 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
  3. pmc Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers
    Juha Lauren
    Cellular Neuroscience, Neurodegeneration and Repair Program, Yale University School of Medicine, New Haven, Connecticut 06536, USA
    Nature 457:1128-32. 2009
  4. ncbi Novel proteinaceous infectious particles cause scrapie
    S B Prusiner
    Science 216:136-44. 1982
  5. pmc Prion-like transmission of protein aggregates in neurodegenerative diseases
    Patrik Brundin
    Patrik Brundin is at the Neuronal Survival Unit, Wallenberg Neuroscience Center, Lund University, BMC A10, 221 84 Lund, Sweden
    Nat Rev Mol Cell Biol 11:301-7. 2010
  6. pmc Structure of the cross-beta spine of amyloid-like fibrils
    Rebecca Nelson
    Howard Hughes Medical Institute, UCLA DOE Institute for Genomics and Proteomics, Box 951570, UCLA, Los Angeles, California 90095 1570, USA
    Nature 435:773-8. 2005
  7. ncbi Atomic structures of amyloid cross-beta spines reveal varied steric zippers
    Michael R Sawaya
    Howard Hughes Medical Institute, UCLA DOE Institute of Genomics and Proteomics, Los Angeles, California 90095 1570, USA
    Nature 447:453-7. 2007
  8. pmc MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response
    Fajian Hou
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Cell 146:448-61. 2011
  9. pmc Prion-like mechanisms in neurodegenerative diseases
    Bess Frost
    Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Nat Rev Neurosci 11:155-9. 2010
  10. pmc Misfolded proteins partition between two distinct quality control compartments
    Daniel Kaganovich
    Department of Biology and BioX Program, Stanford University, Stanford, California 94305, USA
    Nature 454:1088-95. 2008

Detail Information

Publications314 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
    b>Prions are lethal mammalian pathogens composed of aggregated conformational isomers of a host-encoded glycoprotein and which appear to lack nucleic acids...
  2. 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
    ..actively released into the extracellular environment by PrP-expressing cells before and after infection with sheep prions, respectively...
  3. pmc Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers
    Juha Lauren
    Cellular Neuroscience, Neurodegeneration and Repair Program, Yale University School of Medicine, New Haven, Connecticut 06536, USA
    Nature 457:1128-32. 2009
    ..Thus, PrP(C) is a mediator of amyloid-beta-oligomer-induced synaptic dysfunction, and PrP(C)-specific pharmaceuticals may have therapeutic potential for Alzheimer's disease...
  4. ncbi Novel proteinaceous infectious particles cause scrapie
    S B Prusiner
    Science 216:136-44. 1982
    ..Knowledge of the scrapie agent structure may have significance for understanding the causes of several degenerative diseases...
  5. pmc Prion-like transmission of protein aggregates in neurodegenerative diseases
    Patrik Brundin
    Patrik Brundin is at the Neuronal Survival Unit, Wallenberg Neuroscience Center, Lund University, BMC A10, 221 84 Lund, Sweden
    Nat Rev Mol Cell Biol 11:301-7. 2010
    ..The transfer of naked infectious particles between cells could therefore be a target for new disease-modifying therapies...
  6. pmc Structure of the cross-beta spine of amyloid-like fibrils
    Rebecca Nelson
    Howard Hughes Medical Institute, UCLA DOE Institute for Genomics and Proteomics, Box 951570, UCLA, Los Angeles, California 90095 1570, USA
    Nature 435:773-8. 2005
    ..conversion to amyloid-like fibrils is associated with a transmissible infection akin to that caused by mammalian prions. A seven-residue peptide segment from Sup35 forms amyloid-like fibrils and closely related microcrystals, from ..
  7. ncbi Atomic structures of amyloid cross-beta spines reveal varied steric zippers
    Michael R Sawaya
    Howard Hughes Medical Institute, UCLA DOE Institute of Genomics and Proteomics, Los Angeles, California 90095 1570, USA
    Nature 447:453-7. 2007
    ..Structures of 13 of these microcrystals all reveal steric zippers, but with variations that expand the range of atomic architectures for amyloid-like fibrils and offer an atomic-level hypothesis for the basis of prion strains...
  8. pmc MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response
    Fajian Hou
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Cell 146:448-61. 2011
    ..Remarkably, the MAVS fibrils behave like prions and effectively convert endogenous MAVS into functional aggregates...
  9. pmc Prion-like mechanisms in neurodegenerative diseases
    Bess Frost
    Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Nat Rev Neurosci 11:155-9. 2010
    ..in common neurodegenerative diseases--suggest that they share key biophysical and biochemical characteristics with prions. Propagation of protein misfolding in these diseases may therefore occur through mechanisms similar to those that ..
  10. pmc Misfolded proteins partition between two distinct quality control compartments
    Daniel Kaganovich
    Department of Biology and BioX Program, Stanford University, Stanford, California 94305, USA
    Nature 454:1088-95. 2008
    ..Our findings provide a framework for understanding the preferential accumulation of amyloidogenic proteins in inclusions linked to human disease...
  11. 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
    ....
  12. pmc The seeds of neurodegeneration: prion-like spreading in ALS
    Magdalini Polymenidou
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0670, USA
    Cell 147:498-508. 2011
    ..The major neurodegenerative diseases may therefore have mechanistic parallels for non-cell-autonomous spread of disease within the nervous system...
  13. ncbi Prions hijack tunnelling nanotubes for intercellular spread
    Karine Gousset
    Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
    Nat Cell Biol 11:328-36. 2009
    In variant Creutzfeldt-Jakob disease, prions (PrP(Sc)) enter the body with contaminated foodstuffs and can spread from the intestinal entry site to the central nervous system (CNS) by intercellular transfer from the lymphoid system to the ..
  14. pmc A systematic survey identifies prions and illuminates sequence features of prionogenic proteins
    Simon Alberti
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 137:146-58. 2009
    b>Prions are proteins that convert between structurally and functionally distinct states, one or more of which is transmissible. In yeast, this ability allows them to act as non-Mendelian elements of phenotypic inheritance...
  15. pmc Prions are a common mechanism for phenotypic inheritance in wild yeasts
    Randal Halfmann
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 482:363-8. 2012
    The self-templating conformations of yeast prion proteins act as epigenetic elements of inheritance. Yeast prions might provide a mechanism for generating heritable phenotypic diversity that promotes survival in fluctuating environments ..
  16. 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
    ..We term these proteins prionoids, as they appear to infect their neighbors just like prions--but how can bulky protein aggregates be released from cells and how do they access other cells? The widespread ..
  17. ncbi Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]
    Y O Chernoff
    Department of Biological Sciences, University of Illinois, Chicago 60607 7020, USA
    Science 268:880-4. 1995
    The yeast non-Mendelian factor [psi+] has been suggested to be a self-modified protein analogous to mammalian prions. Here it is reported that an intermediate amount of the chaperone protein Hsp104 was required for the propagation of the [..
  18. ncbi Prions: protein aggregation and infectious diseases
    Adriano Aguzzi
    Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    Physiol Rev 89:1105-52. 2009
    ..Finally, we discuss potential antiprion therapies and current developments in the realm of prion diagnostics...
  19. ncbi Prions affect the appearance of other prions: the story of [PIN(+)]
    I L Derkatch
    Laboratory for Molecular Biology, Department of Biological Sciences, University of Illinois at Chicago, 900 South Ashland Avenue, Chicago, IL 60607, USA
    Cell 106:171-82. 2001
    b>Prions are self-propagating protein conformations. Recent research brought insight into prion propagation, but how they first appear is unknown...
  20. pmc Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells
    Christian Münch
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, United Kingdom
    Proc Natl Acad Sci U S A 108:3548-53. 2011
    ..This study reveals that SOD1 aggregates, propagate in a prion-like manner in neuronal cells and sheds light on the mechanisms underlying aggregate uptake and cell-to-cell transfer...
  21. ncbi Scrapie prion protein contains a phosphatidylinositol glycolipid
    N Stahl
    Department of Neurology, University of California, San Francisco 94143
    Cell 51:229-40. 1987
    ..PIPLC catalyzes the release of PrPC from cultured mammalian cells into the medium. These observations indicate that PrPC is anchored to the cell surface by the glycolipid...
  22. ncbi Rnq1: an epigenetic modifier of protein function in yeast
    N Sondheimer
    Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637, USA
    Mol Cell 5:163-72. 2000
    Two protein-based genetic elements (prions) have been identified in yeast. It is not clear whether other prions exist, nor is it understood how one might find them...
  23. pmc Prion-like disorders: blurring the divide between transmissibility and infectivity
    Mimi Cushman
    Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 805b Stellar Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA
    J Cell Sci 123:1191-201. 2010
    b>Prions are proteins that access self-templating amyloid forms, which confer phenotypic changes that can spread from individual to individual within or between species...
  24. pmc Purified and synthetic Alzheimer's amyloid beta (Aβ) prions
    Jan Stöhr
    Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 109:11025-30. 2012
    ..mice accelerated Aβ deposition, suggesting that Aβ aggregates are capable of self-propagation and hence might be prions. Recently, we demonstrated that Aβ deposition can be monitored in live mice using bioluminescence imaging (BLI)...
  25. pmc Cofactor molecules maintain infectious conformation and restrict strain properties in purified prions
    Nathan R Deleault
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Proc Natl Acad Sci U S A 109:E1938-46. 2012
    b>Prions containing misfolded prion protein (PrP(Sc)) can be formed with cofactor molecules using the technique of serial protein misfolding cyclic amplification...
  26. ncbi Nucleated conformational conversion and the replication of conformational information by a prion determinant
    T R Serio
    Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA
    Science 289:1317-21. 2000
    ..This model for replicating protein-based genetic information, nucleated conformational conversion, may be applicable to other protein assembly processes...
  27. pmc Genetic and environmental factors affecting the de novo appearance of the [PSI+] prion in Saccharomyces cerevisiae
    I L Derkatch
    Department of Biological Sciences, University of Illinois at Chicago 60607, USA
    Genetics 147:507-19. 1997
    ....
  28. ncbi An analytical solution to the kinetics of breakable filament assembly
    Tuomas P J Knowles
    Cavendish Laboratory, University of Cambridge, J J Thomson Avenue, Cambridge CB3 0HE, UK
    Science 326:1533-7. 2009
    ....
  29. pmc Peripherally applied Abeta-containing inoculates induce cerebral beta-amyloidosis
    Yvonne S Eisele
    Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, D 72076 Tubingen, Germany
    Science 330:980-2. 2010
    ..We found that intraperitoneal inoculation with β-amyloid-rich extracts induced β-amyloidosis in the brains of β-amyloid precursor protein transgenic mice after prolonged incubation times...
  30. pmc Opposing effects of glutamine and asparagine govern prion formation by intrinsically disordered proteins
    Randal Halfmann
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Mol Cell 43:72-84. 2011
    ..processes as diverse as human protein-folding diseases, bacterial biofilm assembly, and the inheritance of yeast prions (protein-based genetic elements)...
  31. pmc Prion protein interacts with BACE1 protein and differentially regulates its activity toward wild type and Swedish mutant amyloid precursor protein
    Heledd H Griffiths
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 286:33489-500. 2011
    ..Thus, although PrP(C) exerts no control on cleavage of APP(Swe) by BACE1, it has a profound influence on the cleavage of APP(WT), suggesting that PrP(C) may be a key protective player against sporadic Alzheimer disease...
  32. pmc Rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays
    Jason M Wilham
    Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, Hamilton, Montana, United States of America
    PLoS Pathog 6:e1001217. 2010
    ..diagnosis and management of prion diseases is the lack of rapid high-throughput assays to measure low levels of prions. Such measurements have typically required prolonged bioassays in animals...
  33. 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
    b>Prions are composed largely, if not entirely, of prion protein (PrPSc in the case of scrapie)...
  34. ncbi Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion
    Ryuichiro Atarashi
    Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
    Nat Med 17:175-8. 2011
    ..of abnormal conformations of prion protein (PrP(Sc)) has generated the potential for sensitive detection of prions. Here we developed a new PrP(Sc) amplification assay, called real-time quaking-induced conversion (RT-QUIC), which ..
  35. pmc In vivo monitoring of the prion replication cycle reveals a critical role for Sis1 in delivering substrates to Hsp104
    Kimberly A Tipton
    California Institute of Quantitative Biomedical Science, University of California, San Francisco, 1700 4th Street, San Francisco, CA 94158 2542, USA
    Mol Cell 32:584-91. 2008
    b>Prions in Saccharomyces cerevisiae are inherited ordered aggregates reliant upon the disaggregase Hsp104 for stable maintenance. The function of other factors in the natural prion cycle is unclear...
  36. pmc Synthetic amyloid-beta oligomers impair long-term memory independently of cellular prion protein
    Claudia Balducci
    Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan 20156, Italy
    Proc Natl Acad Sci U S A 107:2295-300. 2010
    ..However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Abeta(1-42) oligomers are responsible for cognitive impairment in AD and that PrP(C) is not required...
  37. 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
    b>Prions have been responsible for an entire century of tragic episodes. Fifty years ago, kuru decimated the population of Papua New Guinea. Then, iatrogenic transmission of prions caused more than 250 cases of Creutzfeldt-Jakob disease...
  38. 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
    ..These data suggest that exosomes represent a potent pool of prion infectivity and provide a mechanism for studying prion spread and PrP processing in cells endogenously expressing PrP...
  39. pmc Prion protein and Abeta-related synaptic toxicity impairment
    Anna Maria Calella
    Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland
    EMBO Mol Med 2:306-14. 2010
    ..We report that ablation or overexpression of PrP(C) had no effect on the impairment of hippocampal synaptic plasticity in a transgenic model of AD. These findings challenge the role of PrP(C) as a mediator of Abeta toxicity...
  40. ncbi Secondary structure analysis of the scrapie-associated protein PrP 27-30 in water by infrared spectroscopy
    B W Caughey
    NIAID, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana 59840
    Biochemistry 30:7672-80. 1991
    ..The infrared-based secondary structure compositions were then used as constraints to improve the theoretical localization of the secondary structures within PrP-res 27-30...
  41. pmc Prokaryotic chaperones support yeast prions and thermotolerance and define disaggregation machinery interactions
    Michael Reidy
    Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genetics 192:185-93. 2012
    ..Hsp104 also remodels amyloid in vitro and promotes propagation of amyloid prions in yeast, but ClpB does neither, leading to a view that Hsp104 evolved these activities...
  42. pmc Interaction between prion protein and toxic amyloid β assemblies can be therapeutically targeted at multiple sites
    Darragh B Freir
    Laboratory for Neurodegenerative Research, School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin 4, Republic of Ireland
    Nat Commun 2:336. 2011
    ....
  43. pmc Prions in yeast
    Susan W Liebman
    Department of Biochemistry and Molecular Biology, University of Nevada, Reno, Nevada 89557, USA
    Genetics 191:1041-72. 2012
    ..Indeed, the "protein only" model of prion transmission was first proven using a yeast prion. Typically, known prions are ordered cross-β aggregates (amyloids)...
  44. pmc Familial prion disease with Alzheimer disease-like tau pathology and clinical phenotype
    Suman Jayadev
    Department of Neurology, University of Washington, Seattle, WA, USA
    Ann Neurol 69:712-20. 2011
    ..To describe the Alzheimer disease (AD)-like clinical and pathological features, including marked neurofibrillary tangle (NFT) pathology, of a familial prion disease due to a rare nonsense mutation of the prion gene (PRNP)...
  45. pmc Prion disease blood test using immunoprecipitation and improved quaking-induced conversion
    Christina D Orru
    Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
    MBio 2:e00078-11. 2011
    ..TSEs) or prion diseases in medicine, agriculture, and wildlife biology is the development of practical tests for prions that are at or below infectious levels...
  46. 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
    ..Our data are most consistent with several other risk loci of modest overall effects which will require further genetic association studies to provide definitive evidence...
  47. pmc Prions, prionoids and pathogenic proteins in Alzheimer disease
    Karen H Ashe
    Department of Neurology, N Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN, USA
    Prion 7:55-9. 2013
    ..There is growing evidence that amyloid-β (Aβ) aggregates may be transmissible similar to prions, at least under extreme experimental conditions...
  48. ncbi The physical basis of how prion conformations determine strain phenotypes
    Motomasa Tanaka
    Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California San Francisco and California Institute for Quantitative Biomedical Research, San Francisco, California 94143, USA
    Nature 442:585-9. 2006
    ..Accumulating evidence from yeast prions such as [PSI+] and mammalian prions argues that differences in the prion conformation underlie prion strain ..
  49. ncbi Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformers
    James Shorter
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 304:1793-7. 2004
    ..These Hsp104 activities differed in their reaction mechanism and can explain [PSI+] inheritance patterns...
  50. 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
    ..to be a powerful substrate for both homologous or heterologous PMCA, sustaining the efficient amplification of prions from all the prion sources tested...
  51. 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
    ..For mouse RML (Rocky Mountain Laboratory) prions, the majority of PK-sensitive disease-related PrP isoforms do not appear to contribute significantly to ..
  52. 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
    ..b>Prions from different species vary considerably in their transmissibility to xenogeneic hosts...
  53. ncbi Axonal prion protein is required for peripheral myelin maintenance
    Juliane Bremer
    Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    Nat Neurosci 13:310-8. 2010
    ..These results indicate that neuronal expression and regulated proteolysis of PrP(C) are essential for myelin maintenance...
  54. 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
    ..However, most amyloids appear to lack the natural transmissibility of TSE prions. One feature that distinguishes the latter from the former is the glycophosphatidylinositol membrane anchor on ..
  55. pmc Regulation of embryonic cell adhesion by the prion protein
    Edward Malaga-Trillo
    Department of Biology, University of Konstanz, Konstanz, Germany
    PLoS Biol 7:e55. 2009
    ..Altogether, our data uncover evolutionarily conserved roles of PrP in cell communication, which ultimately impinge on the stability of adherens cell junctions during embryonic development...
  56. pmc The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein
    S Gauczynski
    , Feodor-Lynen Str. 25, D-81377 Munich, Germany
    EMBO J 20:5863-75. 2001
    ..Secretion of an LRP mutant lacking the transmembrane domain (aa 86-101) from BHK cells abolishes PrP binding and internalization. Our results show that LRP/LR acts as the receptor for cellular PrP on the surface of mammalian cells...
  57. ncbi Multiple Gln/Asn-rich prion domains confer susceptibility to induction of the yeast [PSI(+)] prion
    L Z Osherovich
    Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA
    Cell 106:183-94. 2001
    ..These studies suggest a molecular basis for the epigenetic control of [PSI(+)] inducibility and may reveal a broader role for this phenomenon in the physiology of protein aggregation...
  58. ncbi A yeast prion provides a mechanism for genetic variation and phenotypic diversity
    H L True
    Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Illinois 60637, USA
    Nature 407:477-83. 2000
    ..Further, the capacity of [PSI+] to convert previously neutral genetic variation to a non-neutral state may facilitate the evolution of new traits...
  59. pmc NMR solution structure of the human prion protein
    R Zahn
    Institut fur Molekularbiologie und Biophysik, Eidgenossische Technische Hochschule Honggerberg, CH 8093 Zurich, Switzerland
    Proc Natl Acad Sci U S A 97:145-50. 2000
    ....
  60. ncbi Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene
    R Medori
    Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106
    N Engl J Med 326:444-9. 1992
    ..Five other family members who died of this disease, which we termed "fatal familial insomnia," had broader neuropathologic changes suggesting that fatal familial insomnia could be a prion disease...
  61. pmc Genesis and variability of [PSI] prion factors in Saccharomyces cerevisiae
    I L Derkatch
    Department of Biological Sciences, University of Illinois at Chicago 60607, USA
    Genetics 144:1375-86. 1996
    ..We suggest that the different [PSI]-containing derivatives are analogous to the mysterious mammalian prion strains and result from different conformational variants of Sup35p...
  62. 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
    ....
  63. 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...
  64. 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...
  65. pmc Prion protein at the crossroads of physiology and disease
    Emiliano Biasini
    Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA
    Trends Neurosci 35:92-103. 2012
    The presence of the cellular prion protein (PrP(C)) on the cell surface is critical for the neurotoxicity of prions. Although several biological activities have been attributed to PrP(C), a definitive demonstration of its physiological ..
  66. pmc Hsp104, Hsp70 and Hsp40 interplay regulates formation, growth and elimination of Sup35 prions
    James Shorter
    Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Stellar Chance Laboratories, Philadelphia, PA 19104, USA
    EMBO J 27:2712-24. 2008
    ..At high concentrations, Hsp104 eliminates Sup35 prions. This activity is reduced when Ssa1, or enhanced when Ssb1, is incorporated into nascent prions...
  67. pmc Interactions among prions and prion "strains" in yeast
    Michael E Bradley
    Laboratory for Molecular Biology, Department of Biological Sciences, University of Illinois, 900 South Ashland Avenue, Chicago 60607, USA
    Proc Natl Acad Sci U S A 99:16392-9. 2002
    b>Prions are "infectious" proteins. When Sup35, a yeast translation termination factor, is aggregated in its [PSI(+)] prion form its function is compromised...
  68. 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
    b>Prions consist mainly, if not entirely, of PrP(Sc), an aggregated conformer of the host protein PrP(C). Prions come in different strains, all based on the same PrP(C) sequence, but differing in their conformations...
  69. pmc Cellular prion protein is essential for oligomeric amyloid-β-induced neuronal cell death
    Wataru Kudo
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Hum Mol Genet 21:1138-44. 2012
    ..These findings are the first to demonstrate that PrP(C) is required for Aβ oligomer-induced neuronal cell death, the pathology essential to cognitive loss...
  70. pmc Prion hypothesis: the end of the controversy?
    Claudio Soto
    Mitchell Center for Alzheimer s Disease and Related Brain Disorders, Department of Neurology, The University of Texas Medical School at Houston, 6431 Fannin St, Houston, TX 77030, USA
    Trends Biochem Sci 36:151-8. 2011
    ..Future research promises to reveal many more intriguing features about the rogue prions.
  71. 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
    ..For this purpose, we inoculated prions in an Alzheimer's transgenic mouse model that develop typical amyloid plaques and followed the progression of ..
  72. pmc Cellular prion protein regulates beta-secretase cleavage of the Alzheimer's amyloid precursor protein
    Edward T Parkin
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, United Kingdom
    Proc Natl Acad Sci U S A 104:11062-7. 2007
    ..In conclusion, this is a mechanism by which the cellular production of the neurotoxic Abeta is regulated by PrP(C) and may have implications for both Alzheimer's and prion diseases...
  73. pmc Interaction between human prion protein and amyloid-beta (Abeta) oligomers: role OF N-terminal residues
    Shugui Chen
    Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 285:26377-83. 2010
    ..This insight may help explain the interplay between the postulated protective and pathogenic roles of PrP in AD and may contribute to the development of novel therapeutic strategies as well...
  74. pmc Tunnelling nanotubes: a highway for prion spreading?
    Karine Gousset
    Institut Pasteur, Unité de Trafic Membranaire et Pathogénèse, Paris, France
    Prion 3:94-8. 2009
    ..Therefore, we propose a role for TNTs during prion spreading from the periphery to the central nervous system (CNS). Here, we discuss some of the key steps where TNTs might play a role during prion neuroinvasion...
  75. 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
    ..Our studies establish that transmissible prion disease can be induced in wild-type animals by inoculation of rPrP and introduce a valuable new model of prion diseases...
  76. pmc The peculiar nature of unfolding of the human prion protein
    Ilia V Baskakov
    Medical Biotechnology Center, University of Maryland Biotechnology Institute, 725 W Lombard Street, Baltimore, MD 21201, USA
    Protein Sci 13:586-95. 2004
    ..Such behavior is consistent with the thermodynamically variable model, and may be linked to the ability of PrP to adopt distinct abnormal conformations under pathologic conditions...
  77. pmc Suicidal [PSI+] is a lethal yeast prion
    Ryan P McGlinchey
    Laboratory of Biochemistry and Genetics, National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Proc Natl Acad Sci U S A 108:5337-41. 2011
    ..Our findings give a more realistic picture of the impact of the prion change than does focus on "mild" prion variants...
  78. ncbi A cellular gene encodes scrapie PrP 27-30 protein
    B Oesch
    Cell 40:735-46. 1985
    ..No PrP-related nucleic acids were found in purified preparations of scrapie prions, indicating that PrP 27-30 is not encoded by a nucleic acid carried within the infectious particles.
  79. 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...
  80. pmc Newly identified prions in budding yeast, and their possible functions
    Emily T Crow
    Department of Molecular Pharmacology and Biological Chemistry, The Feinberg School of Medicine, Northwestern University, 320 East Superior Street, Chicago, IL 60611, USA
    Semin Cell Dev Biol 22:452-9. 2011
    Yeast prions are atypical genetic elements that are transmitted as heritable protein conformations. [PSI+], [URE3], and [PIN+] are three well-studied prions in the budding yeast, Saccharomyces cerevisiae...
  81. ncbi Characterization of the role of dendritic cells in prion transfer to primary neurons
    Christelle Langevin
    Institut Pasteur, Unité de Trafic Membranaire et Pathogénèse, 25 rue du Dr Roux, Paris Cedex 15, France
    Biochem J 431:189-98. 2010
    ..Additionally, fixed BMDCs also failed to transfer prion infectivity to neurons, suggesting an active transport of prion aggregates, in accordance with a role of TNTs (tunnelling nanotubes) observed in the co-cultures...
  82. pmc Essential role of coiled coils for aggregation and activity of Q/N-rich prions and PolyQ proteins
    Ferdinando Fiumara
    Department of Neuroscience, Columbia University, New York, NY 10032, USA
    Cell 143:1121-35. 2010
    The functional switch of glutamine/asparagine (Q/N)-rich prions and the neurotoxicity of polyQ-expanded proteins involve complex aggregation-prone structural transitions, commonly presumed to be forming β sheets...
  83. 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
    ....
  84. 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...
  85. pmc Analysis of protein levels of 24 cytokines in scrapie agent-infected brain and glial cell cultures from mice differing in prion protein expression levels
    Déborah Tribouillard-Tanvier
    Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
    J Virol 83:11244-53. 2009
    ....
  86. pmc Scrambled prion domains form prions and amyloid
    Eric D Ross
    Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0830, USA
    Mol Cell Biol 24:7206-13. 2004
    ..Sup35p and Rnq1p, although none of the many other yeast Q/N-rich domain proteins have yet been found to be prions. To examine the role of amino acid sequence composition in prion formation, we used Ure2p as a model system and ..
  87. ncbi Reciprocal interference between specific CJD and scrapie agents in neural cell cultures
    Noriuki Nishida
    Yale Medical School, New Haven, CT 06510, USA
    Science 310:493-6. 2005
    ..This relationship between particular strains of sheep- and human-derived agents is likely to affect their prevalence and epidemic spread...
  88. pmc The yeast global transcriptional co-repressor protein Cyc8 can propagate as a prion
    Basant K Patel
    Laboratory for Molecular Biology, Department of Biological Sciences, University of Illinois at Chicago, 900 S Ashland Avenue, Chicago, Illinois 60607, USA
    Nat Cell Biol 11:344-9. 2009
    ..proteins can misfold into a self-seeding amyloid-like conformation, only six are known to be infectious, that is prions. The prions [PSI(+)], [PIN(+)], [URE3], [SWI(+)] and [HET-s] cause distinct heritable physiological changes in ..
  89. 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...
  90. pmc Structural organization of brain-derived mammalian prions examined by hydrogen-deuterium exchange
    Vytautas Smirnovas
    Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, USA
    Nat Struct Mol Biol 18:504-6. 2011
    ....
  91. pmc Huntington toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1
    Anatoli B Meriin
    Boston University School of Medicine, Boston, MA 02118, USA
    J Cell Biol 157:997-1004. 2002
    ..Since Hsp104 is required for prion maintenance in yeast, this suggested a role for prions in polyQ aggregation and toxicity...
  92. pmc Interactome analyses identify ties of PrP and its mammalian paralogs to oligomannosidic N-glycans and endoplasmic reticulum-derived chaperones
    Joel C Watts
    Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada
    PLoS Pathog 5:e1000608. 2009
    ....
  93. 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)...
  94. ncbi Aplysia CPEB can form prion-like multimers in sensory neurons that contribute to long-term facilitation
    Kausik Si
    Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA
    Cell 140:421-35. 2010
    b>Prions are proteins that can assume at least two distinct conformational states, one of which is dominant and self-perpetuating...
  95. 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
    b>Prions are infectious proteins consisting mainly of PrP(Sc), a beta sheet-rich conformer of the normal host protein PrP(C), and occur in different strains. Strain identity is thought to be encoded by PrP(Sc) conformation...
  96. ncbi In vitro conversion of full-length mammalian prion protein produces amyloid form with physical properties of PrP(Sc)
    Olga V Bocharova
    Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA
    J Mol Biol 346:645-59. 2005
    ....
  97. 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
    ..Thus, MG20 cell lines persistently infected with various murine prion strains provide a useful model for the study of the pathogenesis of prion diseases...
  98. ncbi A yeast prion, Mod5, promotes acquired drug resistance and cell survival under environmental stress
    Genjiro Suzuki
    Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Science 336:355-9. 2012
    ..Thus, phenotypic changes caused by active prion conversion under environmental selection may contribute to cellular adaptation in living organisms...
  99. pmc Detection of chronic wasting disease prions in salivary, urinary, and intestinal tissues of deer: potential mechanisms of prion shedding and transmission
    Nicholas J Haley
    Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
    J Virol 85:6309-18. 2011
    Efficient horizontal transmission is a signature trait of chronic wasting disease (CWD) in cervids. Infectious prions shed into excreta appear to play a key role in this facile transmission, as has been demonstrated by bioassays of cervid ..
  100. ncbi Copper is toxic to PrP-ablated mice and exacerbates disease in a mouse model of E200K genetic prion disease
    Tamar Canello
    Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, 91120 Jerusalem, Israel
    Neurobiol Dis 45:1010-7. 2012
    ....
  101. 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
    ..isolates used here revealed that the tg338 mouse line was more versatile and more robust at strain typing ovine prions than tg59 mice...

Research Grants74

  1. Thirteenth Annual Meeting of the Rocky Mountain Virology Association
    Joel Rovnak; Fiscal Year: 2013
    ..Special sessions on HIV pathogenesis, vaccine development, pandemic influenza, prions, virus discovery and the global impact of viral diseases have been featured at past meetings...
  2. Mechanisms of Virus Replication and Gene Expression
    ANNE ELIZABETH SIMON; Fiscal Year: 2013
    ..West Nile, caliciviruses, as well as prions, viroids, fungal hypoviruses, and the model plant viruses Tobacco mosaic virus and Turnip crinkle virus...
  3. NOVEL THERAPEUTICS FOR PRION DISEASES
    Stanley B Prusiner; Fiscal Year: 2013
    b>Prions are infectious proteins that cause age-dependent neurodegeneration in humans and animals...
  4. Impact of Microparticles on Oral TSE Infections
    Joel A Pedersen; Fiscal Year: 2012
    ..We have recently demonstrated that prions bind to soil, clay minerals and silicon dioxide (Johnson et al., 2007)...
  5. Towards Therapeutics for Neurodegenerative Diseases
    Stanley B Prusiner; Fiscal Year: 2013
    ..e., prions (Meyer-Luehmann et al., 2006; Clavaguera et al...
  6. Quantitative analysis of the evolving genotype-to-phenotype map
    DANIEL JAROSZ; Fiscal Year: 2012
    ..Using digital ribosome profiling, yeast and bacterial genetics, and biochemistry I will characterize two prions, [PSI+] and [GAR+], and determine how they affect adaptation to changing environments...
  7. Structure and assembly of the fungal prion HET-s
    William N Wan; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prions are aberrantly folded proteins implicated in the invariably fatal transmissible spongiform encephalopathies (TSEs)...
  8. Ubiquitin and regulation of prion induction by a short-lived protein
    Keith D Wilkinson; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prions are infectious protein isoforms that cause fatal and incurable neurodegenerative diseases in mammals and transmit heritable traits in yeast...
  9. Quantitative analysis of the evolving genotype-to-phenotype map
    DANIEL JAROSZ; Fiscal Year: 2013
    ..Using digital ribosome profiling, yeast and bacterial genetics, and biochemistry I will characterize two prions, [PSI+] and [GAR+], and determine how they affect adaptation to changing environments...
  10. Liposome-siRNA-Peptide Complexes as Therapy to Cure Prion Diseases in Mouse Model
    Mark D Zabel; Fiscal Year: 2013
    ..Infect mice with mouse-adapted strains of scrapie and CWD prions b. Monitor mice for early behavioral and cognitive defects prior to onset of clinical diseas c...
  11. Transmissibility of Neurodegenerative Diseases
    DMITRY Y GOLDGABER; Fiscal Year: 2011
    ..agents of various infectious diseases, as well as of the unconventional infectious agents that we now call prions. While extensive efforts to demonstrate transmissibility were carried out with several LONDs decades ago with ..
  12. Pathogenesis of Chronic Wasting Disease in Transgenic Mice
    DAVIS MARTIN SEELIG; Fiscal Year: 2013
    ..marrow transfer experiments, we hypothesize that marrow of CWD-infected Tg[CerPrP] mice will contain infectious prions, which will be associated with myeloid lineage cells...
  13. MOLECULAR CHAPERONES AND PROTEIN DEGRADATION
    Alfred L Goldberg; Fiscal Year: 2013
    ..We also recently found that prions (PrPSc) aggregates disrupt proteasome function by inhibiting gate opening and substrate entry into the 20S ..
  14. Pathogenesis, Transmission and Detection of Zoonotic Prion Diseases (P01)
    Claudio Soto; Fiscal Year: 2012
    ..goals of this Program Project are to understand the mechanism of transmission and pathogenesis of BSE and CWD prions, to estimate the risk of these infectious agents to propagate disease to other animals and especially to humans, ..
  15. Control of Macromolecular Traffic Through Plasmodesmata
    VITALY H CITOVSKY; Fiscal Year: 2013
    ..Whereas both mammalian and plant pathogens, e.g., prions and (potentially) HIV as well as most plant viruses, utilize cell-to-cell transport pathways, the first such ..
  16. Characteristics of Prion Entry and Neuroinvasion Following Nasal Cavity Infection
    Anthony E Kincaid; Fiscal Year: 2013
    Project Summary/Abstract. The objectives of this project are to determine how prions enter the body, infect lymphoid tissue and travel via peripheral nerves to gain access to the central nervous system where they cause disease...
  17. In Vitro Dissection of Genetic Susceptibility to Prion Disease
    George A Carlson; Fiscal Year: 2011
    ..cultures can be produced from any strain or stock of mice, as well as from other species, and can be infected with prions. Neurosphere cultures provide a new approach to study prion biology and will be developed as a sensitive bioassay...
  18. Development of a Biochemical Diagnosis for Creutzfeldt-Jakob disease
    Claudio Soto; Fiscal Year: 2013
    ..PMCA, has a similar power of amplification as PCR and allowed us to detect, for the first time, prions in blood and urine, even at the pre-symptomatic stages of the disease...
  19. Molecular Mechanisms of Prion and Amyloid Propagation
    Christopher P Jaroniec; Fiscal Year: 2013
    ..Mammalian prions propagate by a mechanism involving the conformational conversion of a largely a-helical cellular prion protein, ..
  20. TRANSGENETIC STUDIES OF PRION DISEASE IN CERVIDS
    Glenn C Telling; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prions cause fatal, incurable, infectious neurodegenerative diseases in animals and humans. Transmission occurs by corruption of cellular prion protein (PrPC) by the pathogenic conformation, PrPSc...
  21. Structural basis of species-specific infectivities of two prion strains
    Peter M Tessier; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Prions are infectious proteins that cause devastating neurodegenerative diseases (transmissible encephalopathies) in humans, cattle and other mammals...
  22. Elucidating the Relations of Heat Shock Factors, Molecular Chaperones and Prions
    Liming Li; Fiscal Year: 2012
    ..in de novo formation and "strain" maintenance of [PSI+];2) to test if HSF and Hsp90 complex regulate other yeast prions. We will investigate if the effects of HSF and Hsp90/cochaperones are [PSI+] specific: 3) to identify additional ..
  23. Phosphorylation of Prion Protein as a novel mechanism for conversion
    Andrea C LeBlanc; Fiscal Year: 2010
    ..We will perform these techniques in systems known to be sensitive to transmissible prions and capable of generating protease-resistant prion protein: normal or mutant prion protein- transfected mouse ..
  24. Mechanisms of prion transport
    Richard A Bessen; Fiscal Year: 2013
    ..In this application, in vivo and in vitro models will be used to investigate transynaptic and axonal transport of prions. The neuromuscular junction, a peripheral synapse, will be used to study transynaptic spread of prions between ..
  25. Absorption, Metabolism and Biodistribution of Prions after Oral Ingestion
    Claudio Soto; Fiscal Year: 2013
    ..b>Prions can infect an individual by various routes, including oral ingestion, enter into the body and remain silently ..
  26. Emergence of drug resistance in prion populations
    Roy G Smith; Fiscal Year: 2013
    Abstract Prions, the pathogens causing transmissible spongiform encephalopathies, are unique in that they consist mainly, if not entirely of multimers of PrPSc, a conformational isomer of the host- encoded protein PrPC...
  27. A new genetic approach for studying prions and other pathogenic protein aggregate
    Ann Hochschild; Fiscal Year: 2011
    Abstract Prions are infectious, self-propagating protein aggregates that have been implicated in a number of devastating neurodegenerative diseases known as transmissible spongiform encephalopathies...
  28. A new genetic approach for studying prions and other pathogenic protein aggregate
    Ann Hochschild; Fiscal Year: 2012
    Abstract Prions are infectious, self-propagating protein aggregates that have been implicated in a number of devastating neurodegenerative diseases known as transmissible spongiform encephalopathies...
  29. PMCA Detection of CWD Infection in Cervid and Non-Cervid Species
    EDWARD ARTHUR HOOVER; Fiscal Year: 2013
    ..We have shown that Infected deer harbor and shed high levels of infectious prions in saliva, blood, urine, and feces, and in the tissues generating those body fluids and excreta, thereby leading ..
  30. Mechanisms of prion aggregation and species barriers
    Christina Sigurdson; Fiscal Year: 2013
    ..We propose to investigate the underlying mechanisms for when and how prions can infect a new host.
  31. Cyclic Amplification of Prion Protein Misfolding
    Claudio Soto; Fiscal Year: 2013
    ..We have described a procedure to replicate prions in vitro with high efficiency...
  32. C. Elegans Model for Neurodegenerative Diseases of Aging
    Richard I Morimoto; Fiscal Year: 2010
    ..Receptor, Ataxin-3, Huntingtin, mutant SOD1, A2 and related amyloidogenic proteins ADan and ABri, and yeast prions (Sup35)...
  33. MURINE TRANSGENIC MODELS OF PRION DISEASES
    David A Harris; Fiscal Year: 2013
    ..Our objective is to understand the molecular and cellular mechanisms by which prions kill neurons and damage the central nervous system...
  34. Investigation of the yeast prion factor [PSI+]
    Susan W Liebman; Fiscal Year: 2012
    ..prion aggregates first arise in cells, what other proteins are associated with them, and how do pre-existing prions enhance the de novo appearance of heterologous prions? Aim I also tests the hypothesis that Sla2, the yeast ..
  35. Defining the mechanistic basis of a prion disaggregase
    James Shorter; Fiscal Year: 2013
    ..which can disaggregate environmentally denatured protein aggregates (like Hsp104), cannot disaggregate amyloids or prions. This Hsp104 activity has enabled yeast to harness multiple prions for beneficial purposes...
  36. UPTAKE, TRANSPORT, AND SPREAD OF PRIONS
    David A Harris; Fiscal Year: 2010
    ..For this reason, a major focus of research in the field has been to understand how prions gain access to the CNS from the periphery, and how they spread within the spinalcord and brain...
  37. Characterization of chaperone-prion specificity in Saccharomyces cerevisiae
    JUSTIN KEITH HINES; Fiscal Year: 2010
    ..Much of what is known about amyloid formation from protein monomers has arisen from studies of the yeast prions which are dependent on molecular chaperone proteins, but the origin of specificity between chaperones and prions ..
  38. DEGENERATIVE AND DEMENTING DISEASES OF AGING
    Stanley B Prusiner; Fiscal Year: 2013
    ..b>Prions seem to be composed solely of PrPSc molecules, which are derived from a precursor PrPc by a poorly understood ..
  39. Protein Conformational Switches
    Susan L Lindquist; Fiscal Year: 2013
    ..shape and to selectively template that change in shape to other proteins of the same type, a property shared by prions and other amyloid-forming proteins across the evolutionary spectrum...
  40. BioCARS: A Synchroton Structural Biology Resource
    JOHN KEITH MOFFAT; Fiscal Year: 2011
    ..of biohazards classified at the BSL-3 level;examples include human pathogenic viruses such as West Nile virus and prions. Others such as anthrax related toxins or enzymes are key to the metabolism of pathogenic microorganisms...
  41. Replication mechanism of human prions
    Witold K Surewicz; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prions, unprecedented among infectious pathogens, are composed of misfolded proteins. Mammalian prions tend to accumulate at high levels in the nervous system, causing fatal neurodegeneration...
  42. C. Elegans Model for Neurodegenerative Diseases of Aging
    Richard I Morimoto; Fiscal Year: 2013
    ..Ataxin-3, Huntingtin, mutant SOD1, A[unreadable] and related amyloidogenic proteins ADan and ABri, and yeast prions (Sup35)...
  43. ION CHANNEL MODULATION BY THE PRION PROTEIN: A NOVEL TOXIC MECHANISM
    David A Harris; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): A great deal is now known about the chemical nature of prions and the mechanism by which they propagate. In contrast, how abnormal forms of the prion protein (PrP) kill nerve cells is still a mystery...
  44. CWD: A Model of Prion Transmission via Saliva and Urine
    NICHOLAS JAMES HALEY; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The levels of infectious prions in animals infected with chronic wasting disease (CWD) in cervids, as with variant Creutzfeldt-Jakob-disease (vCJD) in human, are often beyond the limits of detection ..
  45. Contributions of protein aggregation to gene regulation and phenotypic diversity
    RANDAL ARTHUR HALFMANN; Fiscal Year: 2013
    ..of proteins known to form self-propagating aggregates that act as protein-based elements of inheritance, or prions. By switching to and from its aggregated state, Mot3 broadens the range of phenotypes accessible to clonal yeast ..
  46. Self-Propagating Mechanism of Prion Diseases
    Ilia V Baskakov; Fiscal Year: 2013
    ..Little is known about the molecular aspects of how prions originate and evolve in animals and humans or the principles that underlie the evolution of prion strains...
  47. Molecular Pathogenesis of Age-Dependent CNS Regeneration
    Stanley B Prusiner; Fiscal Year: 2013
    ..For both the mammalian and fungal prions, we have succeeded in producing a variety of synthetic strains...
  48. BioCARS: A Synchroton Structural Biology Resource
    JOHN KEITH MOFFAT; Fiscal Year: 2012
    ..of biohazards classified at the BSL-3 level; examples include human pathogenic viruses such as West Nile virus and prions. Others such as anthraxrelated toxins or enzymes are key to the metabolism of pathogenic microorganisms...
  49. A Prion Reveals Complex Traits and Phenotypic Diversity
    HEATHER L TRUE-KROB; Fiscal Year: 2013
    ..Due to their unique mode of propagation and inheritance, these prions have a profound impact on the ability of the organism to alter its phenotypes and adapt to changing environments...
  50. Origin and Mechanism of Promiscuous Prion Strains
    Surachai Supattapone; Fiscal Year: 2013
    ..We recently reported that cofactor molecules regulate the major strain properties of mammalian prions, including neurotropism and PrPSc conformation...
  51. Pathogenicity of prion protein aggregates from uninfected cells and brains
    Wen Quan Zou; Fiscal Year: 2013
    ..partially proteinase K (PK)-resistant aggregated prion protein (PrPSc) constitutes the major component of prions that cause a group of fatal transmissible spongiform encephalopathies or prion diseases in animals and humans...
  52. Generation of Tau Prion Strains in Dividing Mammalian Cells
    DAVID WINLAND SANDERS; Fiscal Year: 2013
    ..However, whether or not the proteins associated with these diverse diseases are true prions, defined by the ability to propagate unique conformations, is an unsettled matter...
  53. The determinants of aggregation and toxicity of prion-like domains
    Eric D Ross; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prions are infectious proteins that result from the structural conversion of proteins into a self-templating conformation...
  54. Characterization of de novo generation of infectious prions
    Joaquin Castilla; Fiscal Year: 2009
    ..In addition, the in vitro generated prions possess key prion features, i.e., they are infectious in vivo and maintain their prion strain specificity...
  55. Mechanisms of prion spread
    Christina Sigurdson; Fiscal Year: 2013
    ..b>Prions are the only protein aggregates that are naturally transmitted as an infectious disease, and most recently, human ..
  56. Elucidating factors involved in formation and propagation of yeast prion strains
    Kevin C Stein; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Prions are proteins that self-propagate an aggregated or amyloid-like structure that converts protein from its native state to this aggregated conformation...
  57. Functional Diversity of J-protein Components of Hsp70 Chaperone Machinery
    Elizabeth A Craig; Fiscal Year: 2012
    ..To understand the specificity of Sis1, its function in the propagation of yeast prions will be exploited, as it is specifically required for fragmentation of prion complexes...
  58. The Role of Competitive Forces in Prion Propagation and Appearance
    Tricia R Serio; Fiscal Year: 2013
    ..To directly test this hypothesis, we will determine: 1) the pathways by which dominant-negative mutants cure prions, 2) the pathways by which prion variants establish dominance, and 3) the molecular basis of the requirement for an ..
  59. Structure and Mechanism of a Prion-remodeling Factor
    Francis T F Tsai; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prions are unconventional, highly infectious agents, which are composed entirely of a protein that adopts an abnormal conformation...
  60. Regulation of Amyloid Fibril Assembly by Hsp40 Molecular Chaperones
    Daniel W Summers; Fiscal Year: 2010
    ..Budding yeast possess several endogenous proteins called prions that assemble into intracellular, amyloid-like fibrils...
  61. Detection and structural analysis of misfolded proteins causing neurodegeneration
    David W Colby; Fiscal Year: 2012
    ..An analogous assay for detecting prions had femtogram sensitivity (Colby et. al., PNAS, 2007)...
  62. Hsp40 and conformational disease
    Douglas M Cyr; Fiscal Year: 2011
    ..b>Prions are infectious proteins that that assemble into a self-perpetuating amyloid-like state that is associated with ..
  63. PrP-scrapie transport across intestinal & BBB
    Neena Singh; Fiscal Year: 2007
    ..by intra-venous inoculation of peripheral blood to experimental animals raises two important questions: 1) how are prions from food transported across the intestinal epithelial barrier, and 2) how do prions in the peripheral blood cross ..
  64. Assessing the Transmissibility of CWD to Humans
    Qingzhong Kong; Fiscal Year: 2010
    ..CWD transmission to humans and to establish a surveillance program to monitor for human subjects infected by CWD prions. Research Design: For Aims 1 and 2, humanized and cervidized Tg mice will be intracerebrally (i.e...
  65. Biochemical Detection of Prions in Blood
    Joaquin Castilla; Fiscal Year: 2005
    ..PMCA has tremendous promise to increase detection of prions in tissues and biological fluids during early stages of the disease and thus may be useful for pre-symptomatic ..
  66. CNS DEGENERATION CAUSED BY NOVEL PATHOGENS
    STANLEY PRUSINER; Fiscal Year: 1993
    b>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...
  67. 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]..
  68. MOLECULAR DETERMINANTS OF HUMAN PRION DISEASES
    James Mastrianni; Fiscal Year: 2000
    The objectives of 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...
  69. Preventing Human Prion Diseases - Inactivation of Prions
    Stanley B Prusiner; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Prions are infectious proteins that cause neurodegenerative diseases in humans and animals...
  70. TRANSMISSIBLE AND GENETIC NEURODENGENERATIVE DISEASES
    STANLEY PRUSINER; Fiscal Year: 1999
    ..These results are of considerable importance, as the number of hypotheses available to explain strains of prions continues to shrink...
  71. Interaction of Prions with Dendritic Cells
    Michael Green; Fiscal Year: 2004
    ..An increased understanding of the way in which prions, unusual "protein only" infectious agents, cause disease may allow us to develop ways to enhance our biological ..
  72. Recombinant human serum albumin for use in cell culture media
    Ning Huang; Fiscal Year: 2007
    ..However, the use of pHSA carries the risk of transmission of virus and emerging infectious pathogens, such as prions, from blood for which no tests are available...
  73. Structural Investigations of the Prion Protein het-s
    Roland Riek; Fiscal Year: 2006
    ..Thus, prions are infectious proteins which propagate by converting the normal form of the protein into an altered beta-sheet-..
  74. EXPRESSION OF GLYCOLIPID ANCHORED PRIONS IN TRYPANOSOMES
    GEORGE CROSS; Fiscal Year: 2001
    ..1 percent of the total cellular protein. Despite the accumulated knowledge implicating prions or mutant prion genes in several encephalopathies, the central theory - that prion propagation involves a self-..