Advertisement

Prion Protein and the Molecular Features of Transmissible Spongiform Encephalopathy Agents

  • J. R. Silveira
  • B. Caughey
  • G. S. Baron
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 284)

Abstract

Transmissible spongiform encephalopathy (TSE) diseases, or prion diseases, are neurodegenerative diseases found in a number of mammals, including man. Although they are generally rare, TSEs are always fatal, and as of yet there are no practical therapeutic avenues to slow the course of disease. The epidemic of bovine spongiform encephalopathy (BSE) in the UK greatly increased the awareness of TSE diseases. Although it appears that BSE has not spread to North America, chronic wasting disease (CWD), a TSE found in cervids, is causing significant concern. Despite decades of investigation, the exact nature of the infectious agent of the TSEs is still controversial. Although many questions remain, substantial efforts have been made to understand the molecular features of TSE agents, with the hope of enhancing diagnosis and treatment of disease, as well as understanding the fundamental nature of the infectious agent itself. This review summarizes the current understanding of these molecular features, focusing on the role of the prion protein (PrPC) and its relationship to the disease-associated isoform (PrPsc)

Keywords

Prion Protein Bovine Spongiform Encephalopathy Chronic Wasting Disease Protein Misfolding Cyclic Amplification Scrapie Prion Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. DEFRA BSE information General statistics-GB HM Government UK Online-Department for Environment Food and Rural Affairs.http://www.defra.gov.uk/animalh/bse/bse-statistics/bse/general.html
  2. UK Monthly CJD statistics UK-Department of Health.http://www.doh.gov.uk/cjd/ cjd_stat.htm
  3. Andreoletti O, Lacroux C, Chabert A, Monnereau L, Tabouret G, Lantier F, Berthon P, Eychenne F, Lafond-Benestad S, Elsen JM, Schelcher F (2002) PrP(Sc) accumulation in placentas of ewes exposed to natural scrapie: influence of foetal PrP genotype and effect on ewe-to-lamb transmission. J Gen Virol 83: 2607–2616PubMedGoogle Scholar
  4. Asante EA, Collinge J (2001) Transgenic studies of the influence of the PrP structure on TSE diseases. Adv Protein Chem 57: 273–311PubMedCrossRefGoogle Scholar
  5. Baron GS, Caughey B (2003) Effect of Glycosylphosphatidylinositol Anchor-dependent and -independent Prion Protein Association with Model Raft Membranes on Conversion to the Protease-resistant Isoform. J Biol Chem 278: 14883–14892PubMedCrossRefGoogle Scholar
  6. Baron G S, Wehrly K, Dorward D W, Chesebro B, Caughey B (2002) Conversion of raft associated prion protein to the protease-resistant state requires insertion of PrP-res ( PrP(Sc)) into contiguous membranes. EMBO J 21: 1031–1040Google Scholar
  7. Bartz J C, Bessen RA, McKenzie D, Marsh RF, Aiken JM (2000) Adaptation and selection of prion protein strain conformations following interspecies transmission of transmissible mink encephalopathy. J Virol 74: 5542–5547PubMedCrossRefGoogle Scholar
  8. Bartz JC, Marsh RF, McKenzie DI, Aiken JM (1998) The host range of chronic wasting disease is altered on passage in ferrets. Virology 251: 297–301PubMedCrossRefGoogle Scholar
  9. Baskakov I V, Legname G, Baldwin MA, Prusiner SB, Cohen FE (2002) Pathway com- plexity of prion protein assembly into amyloid. J Biol Chem 277: 21140–21148PubMedCrossRefGoogle Scholar
  10. Basler K, Oesch B, Scott M, Westaway D, Walchli M, Groth D F, McKinley M P, Prusiner S B, Weissmann C (1986) Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell 46: 417–428PubMedCrossRefGoogle Scholar
  11. Baylis M, Houston F, Kao RR, McLean AR, Hunter N, Gravenor MB (2002) BSE—a wolf in sheep’s clothing? Trends Microbiol 10: 563–570PubMedCrossRefGoogle Scholar
  12. Belay ED, Gambetti P, Schonberger LB, Parchi P, Lyon DR, Capellari S, McQuiston JH, Bradley K, Dowdle G, Crutcher JM, Nichols CR (2001) Creutzfeldt-Jakob disease in unusually young patients who consumed venison. Arch Neurol 58: 16731678Google Scholar
  13. Bessen RA, Kocisko DA, Raymond GJ, Nandan S, Lansbury PT, Caughey B (1995) Non-genetic propagation of strain-specific properties of scrapie prion protein. Nature 375: 698–700PubMedCrossRefGoogle Scholar
  14. Bessen RA, Marsh RF (1992) Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent. J Virol 66: 2096–2101PubMedGoogle Scholar
  15. Bessen RA, Marsh RF (1994) Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy. J Virol 68: 7859–7868PubMedGoogle Scholar
  16. Bessen RA, Raymond GJ, Caughey B (1997) In situ formation of protease-resistant prion protein in transmissible spongiform encephalopathy-infected brain slices. J Biol Chem 272: 15227–15231PubMedCrossRefGoogle Scholar
  17. Bolton DC, Bendheim PE (1988) A modified host protein model of scrapie. In: Bock G, Marsh J (eds) Novel Infectious Agents and the Central Nervous System. John Wiley and Sons, Chichester, pp 164–181Google Scholar
  18. Bolton DC, Bendheim PE, Marmorstein AD, Potempska A (1987) Isolation and structural studies of the intact scrapie agent protein. Arch Biochem Biophys 258: 579590Google Scholar
  19. Borchelt DR, Scott M, Taraboulos A, Stahl N, Prusiner SB (1990) Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells. J Cell Biol 110: 743–752PubMedCrossRefGoogle Scholar
  20. Borchelt DR, Taraboulos A, Prusiner SB (1992) Evidence for synthesis of scrapie prion proteins in the endocytic pathway. J Biol Chem 267: 16188–16199PubMedGoogle Scholar
  21. Bosque PJ, Ryou C, Telling G, Peretz D, Legname G, DeArmond SJ, Prusiner SB (2002) Prions in skeletal muscle. Proc Natl Acad Sci USA 99: 3812–3817PubMedCrossRefGoogle Scholar
  22. Bossers A, Belt PBGM, Raymond GJ, Caughey B, de Vries R, Smits MA (1997) Scrapie susceptibility-linked polymorphisms modulate the in vitro conversion of sheep prion protein to protease-resistant forms. Proc Natl Acad Sci USA 94: 49314936Google Scholar
  23. Bossers A, de Vries R, Smits MA (2000) Susceptibility of sheep for scrapie as assessed by in vitro conversion of nine naturally occurring variants of PrP. J Virol 74: 1407–1414PubMedCrossRefGoogle Scholar
  24. Bounhar Y, Zhang Y, Goodyer CG, LeBlanc A (2001) Prion protein protects human neurons against Bax-mediated apoptosis. J Biol Chem 276: 39145–39149PubMedCrossRefGoogle Scholar
  25. Brown DR, Qin K, Herms JW, Madlung A, Manson J, Strome R, Fraser PE, Kruck T, von Bohlen A, Schulz-Schaeffer W, Giese A, Westaway D, Kretzschmar H (1997) The cellular prion protein binds copper in vivo. Nature 390: 684–687PubMedCrossRefGoogle Scholar
  26. Brown DR, Wong BS, Hafiz F, Clive C, Haswell SJ, Jones IM (1999) Normal prion pro-Google Scholar
  27. tein has an activity like that of superoxide dismutase. Biochem J 344 Pt 1:1–5 Bruce ME, Fraser H (1991) Scrapie strain variation and its implications. Curr Top Microbiol Immunol 172: 125–138Google Scholar
  28. Bruce ME, Will RG, Ironside JW, McConnell I, Drummond D, Suttie A, McCardle L, Chree A, Hope J, Birkett C, Cousens S, Fraser H, Bostock CJ (1997) Transmissions to mice indicate that `new variant’ CJD is caused by the BSE agent. Nature 389: 498–501PubMedCrossRefGoogle Scholar
  29. Bueler H, Aguzzi A, Sailer A, Greiner RA, Autenried P, Aguet M, Weissmann C (1993) Mice devoid of PrP are resistant to scrapie. Cell 73: 1339–1347PubMedCrossRefGoogle Scholar
  30. Callahan MA, Xiong L, Caughey B (2001) Reversibility of scrapie-associated prion protein aggregation. J Biol Chem 276: 28022–28028PubMedCrossRefGoogle Scholar
  31. Cashman NR, Loertscher R, Nalbantoglu J, Shaw I, Kascsak RJ, Bolton DC, Bend-heim PE (1990) Cellular isoform of the scrapie agent protein participates in lymphocyte activation. Cell 61: 185–192PubMedCrossRefGoogle Scholar
  32. Caughey B (2001) Interactions between prion protein isoforms: the kiss of death? Trends Biochem Sci 26: 235–242PubMedCrossRefGoogle Scholar
  33. Caughey B, Kocisko DA, Raymond GJ, Lansbury PT, Jr. (1995) Aggregates of scrapieassociated prion protein induce the cell-free conversion of protease-sensitive prion protein to the protease-resistant state. Chem Biol 2: 807–817PubMedCrossRefGoogle Scholar
  34. Caughey B, Lansbury PT Jr (2003) Protofibrils, Pores, Fibrils, and Neurodegeneration: Separating the Responsible Protein Aggregates from the Innocent Bystanders. Annu Rev Neurosci 26: 267–298Google Scholar
  35. Caughey B, Neary K, Buller R, Ernst D, Perry LL, Chesebro B, Race RE (1990) Normal and scrapie-associated forms of prion protein differ in their sensitivities to phospholipase and proteases in intact neuroblastoma cells. J Virol 64: 1093–1101PubMedGoogle Scholar
  36. Caughey B, Race RE, Ernst D, Buchmeier MJ, Chesebro B (1989) Prion protein biosynthesis in scrapie-infected and uninfected neuroblastoma cells. J Virol 63: 175181Google Scholar
  37. Caughey B, Race RE, Vogel M, Buchmeier MJ, Chesebro B (1988) In vitro expression in eukaryotic cells of a prion protein gene cloned from scrapie-infected mouse brain. Proc Natl Acad Sci USA 85: 4657–4661PubMedCrossRefGoogle Scholar
  38. Caughey B, Raymond GJ (1991) The scrapie-associated form of PrP is made from a cell surface precursor that is both protease-and phospholipase-sensitive. J Biol Chem 266: 18217–18223PubMedGoogle Scholar
  39. Caughey B, Raymond GJ, Bessen RA (1998a) Strain-dependent differences in beta- sheet conformations of abnormal prion protein. J Biol Chem 273: 32230–32235PubMedCrossRefGoogle Scholar
  40. Caughey B, Raymond GJ, Ernst D, Race RE (1991a) N-terminal truncation of the scrapie-associated form of PrP by lysosomal protease(s): implications regarding the site of conversion of PrP to the protease-resistant state. J Virol 65: 6597–6603PubMedGoogle Scholar
  41. Caughey B, Raymond GJ, Kocisko DA, Lansbury PT, Jr. (1997) Scrapie infectivity correlates with converting activity, protease resistance, and aggregation of scrapie-associated prion protein in guanidine denaturation studies. J Virol 71: 41074110Google Scholar
  42. Caughey B, Raymond LD, Raymond GJ, Maxson L, Silveira J, Baron GS (2003) Inhibition of protease-resistant prion protein accumulation in vitro by curcumin. J Virol 77: 5499–5502PubMedCrossRefGoogle Scholar
  43. Caughey BW, Dong A, Bhat KS, Ernst D, Hayes SF, Caughey WS (1991b) Secondary structure analysis of the scrapie-associated protein PrP 27–30 in water by infrared spectroscopy. Biochemistry 30: 7672–7680PubMedCrossRefGoogle Scholar
  44. Caughey WS, Raymond LD, Horiuchi M, Caughey B (1998b) Inhibition of protease-resistant prion protein formation by porphyrins and phthalocyanines. Proc Natl Acad Sci USA 95: 12117–12122PubMedCrossRefGoogle Scholar
  45. Chabry J, Caughey B, Chesebro B (1998) Specific inhibition of in vitro formation of protease-resistant prion protein by synthetic peptides. J Biol Chem 273: 1320313207Google Scholar
  46. Chabry J, Priola SA, Wehrly K, Nishio J, Hope J, Chesebro B (1999) Species-independent inhibition of abnormal prion protein ( PrP) formation by a peptide containing a conserved PrP sequence. J Virol 73: 6245–6250Google Scholar
  47. Chernoff YO, Lindquist SL, Ono B, Inge-Vechtomov SG, Liebman SW (1995) Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]. Science 268: 880–884PubMedCrossRefGoogle Scholar
  48. Chesebro B (1999) Prion protein and the transmissible spongiform encephalopathy diseases. Neuron 24: 503–506PubMedCrossRefGoogle Scholar
  49. Chiarini LB, Freitas AR, Zanata SM, Brentani RR, Martins VR, Linden R (2002) Cellular prion protein transduces neuroprotective signals. EMBO J 21: 3317–3326PubMedCrossRefGoogle Scholar
  50. Chiesa R, Drisaldi B, Quaglio E, Migheli A, Piccardo P, Ghetti B, Harris DA (2000) Accumulation of protease-resistant prion protein ( PrP) and apoptosis of cerebellar granule cells in transgenic mice expressing a PrP insertional mutation. Proc Natl Acad Sci USA 97: 5574–5579Google Scholar
  51. Chiesa R, Piccardo P, Ghetti B, Harris DA (1998) Neurological illness in transgenic mice expressing a prion protein with an insertional mutation. Neuron 21: 13391351Google Scholar
  52. Collinge J, Palmer MS, Dryden AJ (1991) Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. Lancet 337: 1441–1442PubMedCrossRefGoogle Scholar
  53. Collinge J, Sidle KC, Meads J, Ironside J, Hill AF (1996) Molecular analysis of prion strain variation and the aetiology of `new variant’ CJD. Nature 383: 685–690PubMedCrossRefGoogle Scholar
  54. Comincini S, Foti MG, Tranulis MA, Hills D, Di Guardo G, Vaccari G, Williams JL, Harbitz I, Ferretti L (2001) Genomic organization, comparative analysis, and genetic polymorphisms of the bovine and ovine prion Doppel genes ( PRND ). Mamm Genome 12: 729–733Google Scholar
  55. Cutlip RC, Miller JM, Race RE, Jenny AL, Katz JB, Lehmkuhl HD, DeBey BM, Robinson MM (1994) Intracerebral transmission of scrapie to cattle. J Infect Dis 169: 814–820PubMedCrossRefGoogle Scholar
  56. DebBurman SK, Raymond GJ, Caughey B, Lindquist S (1997) Chaperone-supervised conversion of prion protein to its protease-resistant form. Proc Nail Acad Sci USA 94: 13938–13943CrossRefGoogle Scholar
  57. Demaimay R, Harper J, Gordon H, Weaver D, Chesebro B, Caughey B (1998) Structural aspects of Congo red as an inhibitor of protease-resistant prion protein formation. J Neurochem 71: 2534–2541PubMedCrossRefGoogle Scholar
  58. Dickinson AG (1976) Scrapie in sheep and goats. In: Kimberlin RH (eds) Slow virus diseases of animals and man. North-Holland Publishing Company, Amsterdam, pp 209–241Google Scholar
  59. Dickinson AG, Meikle VM, Fraser H (1968) Identification of a gene which controls the incubation period of some strains of scrapie agent in mice. J Comp Pathol 78: 293–299PubMedCrossRefGoogle Scholar
  60. Diringer H, Gelderblom H, Hilmert H, Ozel M, Edelbluth C, Kimberlin RH (1983) Scrapie infectivity, fibrils and low molecular weight protein. Nature 306: 476–478PubMedCrossRefGoogle Scholar
  61. Donne DG, Viles JH, Groth D, Mehlhorn I, James TL, Cohen FE, Prusiner SB, Wright PE, Dyson HJ (1997) Structure of the recombinant full-length hamster prion protein PrP(29–231): the N terminus is highly flexible. Proc Natl Acad Sci USA 94: 13452–13457CrossRefGoogle Scholar
  62. Eigen M (1996) Prionics or the kinetic basis of prion diseases. Biophys Chem 63: A118CrossRefGoogle Scholar
  63. Enari M, Flechsig E, Weissmann C (2001) Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells abrogated by exposure to a prion protein antibody. Proc Natl Acad Sci USA 98: 9295–9299PubMedCrossRefGoogle Scholar
  64. Flechsig E, Shmerling D, Hegyi I, Raeber AJ, Fischer M, Cozzio A, von Mering C, Aguzzi A, Weissmann C (2000) Prion protein devoid of the octapeptide repeat region restores susceptibility to scrapie in PrP knockout mice. Neuron 27: 399–408PubMedCrossRefGoogle Scholar
  65. Fraser H, Bruce ME, Chree A, McConnell I, Wells GA (1992) Transmission of bovine spongiform encephalopathy and scrapie to mice. J Gen Virol 73 (Pt 8): 1891–1897PubMedCrossRefGoogle Scholar
  66. Gajdusek DC (1988) Transmissible and non-transmissible amyloidoses: autocatalytic post-translational conversion of host precursor proteins to beta-pleated sheet configurations. J Neuroimmunol 20: 95–110PubMedCrossRefGoogle Scholar
  67. Giaccone G, Verga L, Bugiani O, Frangione B, Serban D, Prusiner SB, Farlow MR, Ghetti B, Tagliavini F (1992) Prion protein preamyloid and amyloid deposits in Gerstmann-Straussler-Scheinker disease, Indiana kindred. Proc Natl Acad Sci USA 89: 9349–9353Google Scholar
  68. Gibbs CJ, Jr., Safar J, Ceroni M, Di Martino A, Clark WW, Hourrigan JL (1990) Experimental transmission of scrapie to cattle. Lancet 335: 1275PubMedCrossRefGoogle Scholar
  69. Graner E, Mercadante AF, Zanata SM, Forlenza OV, Cabral AL, Veiga SS, Juliano MA, Roesler R, Walz R, Minetti A, Izquierdo I, Martins VR, Brentani RR (2000) Cellular prion protein binds laminin and mediates neuritogenesis. Brain Res Mol Brain Res 76: 85–92PubMedCrossRefGoogle Scholar
  70. Griffith JS (1967) Self-replication and scrapie. Nature 215: 1043–1044PubMedCrossRefGoogle Scholar
  71. Guiroy DC, Liberski PP, Williams ES, Gajdusek DC (1994) Electron microscopic findings in brain of Rocky Mountain elk with chronic wasting disease. Folia Neuropathol 32: 171–173PubMedGoogle Scholar
  72. Guiroy DC, Williams ES, Song KJ, Yanagihara R, Gajdusek DC (1993) Fibrils in brain of Rocky Mountain elk with chronic wasting disease contain scrapie amyloid. Acta Neuropathol (Berl) 86: 77–80CrossRefGoogle Scholar
  73. Guiroy DC, Williams ES, Yanagihara R, Gajdusek DC (1991) Topographic distribution of scrapie amyloid-immunoreactive plaques in chronic wasting disease in captive mule deer ( Odocoileus hemionus hemionus ). Acta Neuropathol (Berl) 81: 475–478Google Scholar
  74. Hamir AN, Cutlip RC, Miller JM, Williams ES, Stack MJ, Miller MW, O’Rourke KI, Chaplin MJ (2001) Preliminary findings on the experimental transmission of chronic wasting disease agent of mule deer to cattle. J Vet Diagn Invest 13: 91–96PubMedCrossRefGoogle Scholar
  75. Hegde RS, Tremblay P, Groth D, DeArmond SJ, Prusiner SB, Lingappa VR (1999) Transmissible and genetic prion diseases share a common pathway of neurodegeneration. Nature 402: 822–826PubMedCrossRefGoogle Scholar
  76. Heppner F, Musahl C, Arrighi I, Klein MA, Rulicke T, Oesch B, Zinkernagel RM, Kalinke U, Aguzzi A (2001) Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies. Science 294: 178–189PubMedCrossRefGoogle Scholar
  77. Herrmann LM, Caughey B (1998) The importance of the disulfide bond in prion protein conversion. Neuroreport 9: 2457–2461PubMedCrossRefGoogle Scholar
  78. Hill AF, Antoniou M, Collinge J (1999) Protease-resistant prion protein produced in vitro lacks detectable infectivity. J Gen Virol 80 (Pt 1): 11–14PubMedGoogle Scholar
  79. Hill AF, Desbruslais M, Joiner S, Sidle KC, Gowland I, Collinge J, Doey LJ, Lantos P (1997) The same prion strain causes vCJD and BSE. Nature 389: 448–450PubMedCrossRefGoogle Scholar
  80. Holscher C, Delius H, Burkle A (1998) Overexpression of nonconvertible PrPc deltal14–121 in scrapie-infected mouse neuroblastoma cells leads to trans-dominant inhibition of wild-type PrP(Sc) accumulation. J Virol 72: 1153–1159PubMedGoogle Scholar
  81. Hope J (1994) The nature of the scrapie agent: the evolution of the virino. Ann N Y Acad Sci 724: 282–289PubMedCrossRefGoogle Scholar
  82. Hope J, Morton LJ, Farquhar CF, Multhaup G, Beyreuther K, Kimberlin RH (1986) The major polypeptide of scrapie-associated fibrils (SAF) has the same size, charge distribution and N-terminal protein sequence as predicted for the normal brain protein ( PrP ). EMBO J 5: 2591–2597Google Scholar
  83. Hope J, Multhaup G, Reekie LJ, Kimberlin RH, Beyreuther K (1988) Molecular pathology of scrapie-associated fibril protein (PrP) in mouse brain affected by the ME7 strain of scrapie. Eur J Biochem 172: 271–277PubMedCrossRefGoogle Scholar
  84. Hope J, Wood SC, Birkett CR, Chong A, Bruce ME, Cairns D, Goldmann W, Hunter N, Bostock CJ (1999) Molecular analysis of ovine prion protein identifies similarities between BSE and an experimental isolate of natural scrapie, CH1641. J Gen Virol 80 (Pt 1): 1–4PubMedGoogle Scholar
  85. Horiuchi M, Baron GS, Xiong LW, Caughey B (2001) Inhibition of interactions and interconversions of prion protein isoforms by peptide fragments from the C-terminal folded domain. J Biol Chem 276: 15489–15497PubMedCrossRefGoogle Scholar
  86. Horiuchi M, Caughey B (1999a) Prion protein interconversions and the transmissible spongiform encephalopathies. Structure Fold Des 7: R231 - R240PubMedCrossRefGoogle Scholar
  87. Horiuchi M, Caughey B (1999b) Specific binding of normal prion protein to the scrapie form via a localized domain initiates its conversion to the protease-resistant state. EMBO J 18: 3193–3203PubMedCrossRefGoogle Scholar
  88. Horiuchi M, Nemoto T, Ishiguro N, Furuoka H, Mohri S, Shinagawa M (2002) Biological and biochemical characterization of sheep scrapie in Japan. J Clin Microbiol 40: 3421–3426PubMedCrossRefGoogle Scholar
  89. Horiuchi M, Priola SA, Chabry J, Caughey B (2000) Interactions between heterologous forms of prion protein: binding, inhibition of conversion, and species barriers. Proc Natl Acad Sci USA 97: 5836–5841PubMedCrossRefGoogle Scholar
  90. Hornemann S, Glockshuber R (1998) A scrapie-like unfolding intermediate of the prion protein domain PrP(121–231) induced by acidic pH. Proc Natl Acad Sci USA 95: 6010–6014PubMedCrossRefGoogle Scholar
  91. Hornemann S, Korth C, Oesch B, Riek R, Wider G, Wuthrich K, Glockshuber R (1997) Recombinant full-length murine prion protein, mPrP(23–231): purification and spectroscopic characterization. FEBS Lett 413: 277–281PubMedCrossRefGoogle Scholar
  92. Hornshaw MP, McDermott JR, Candy JM (1995) Copper binding to the N-terminal tandem repeat regions of mammalian and avian prion protein. Biochem Biophys Res Commun 207: 621–629PubMedCrossRefGoogle Scholar
  93. Hunter N, Goldmann W, Smith G, Hope J (1994) Frequencies of PrP gene variants in healthy cattle and cattle with BSE in Scotland. Vet Rec 135: 400–403PubMedCrossRefGoogle Scholar
  94. Jackson GS, Hosszu LL, Power A, Hill AF, Kenney J, Saibil H, Craven CJ, Waltho JP, Clarke AR, Collinge J (1999) Reversible conversion of monomeric human prion protein between native and fibrilogenic conformations. Science 283: 1935–1937PubMedCrossRefGoogle Scholar
  95. Jackson GS, Murray I, Hosszu LL, Gibbs N, Waltho JP, Clarke AR, Collinge J (2001) Location and properties of metal-binding sites on the human prion protein. Proc Natl Acad Sci USA 98: 8531–8535PubMedCrossRefGoogle Scholar
  96. Jarrett JT, Lansbury PT, Jr. (1993) Seeding “one-dimensional crystallization” of amyloid: a pathogenic mechanism in Alzheimer’s disease and scrapie? Cell 73: 10551058Google Scholar
  97. Jeffrey M, Goodsir CM, Bruce ME, McBride PA, Farquhar C (1994) Morphogenesis of amyloid plaques in 87 V murine scrapie. Neuropathol Appl Neurobiol 20: 535–542PubMedCrossRefGoogle Scholar
  98. Kaneko K, Peretz D, Pan KM, Blochberger TC, Wille H, Gabizon R, Griffith OH, Cohen FE, Baldwin MA, Prusiner SB (1995) Prion protein ( PrP) synthetic peptides induce cellular PrP to acquire properties of the scrapie isoform. Proc Natl Acad Sci USA 92: 11160–11164Google Scholar
  99. Kaneko K, Vey M, Scott M, Pilkuhn S, Cohen FE, Prusiner SB (1997a) COOH-terminal sequence of the cellular prion protein directs subcellular trafficking and controls conversion into the scrapie isoform. Proc Natl Acad Sci USA 94: 2333–2338PubMedCrossRefGoogle Scholar
  100. Kaneko K, Wille H, Mehlhorn I, Zhang H, Ball H, Cohen FE, Baldwin MA, Prusiner SB (1997b) Molecular properties of complexes formed between the prion protein and synthetic peptides. J Mol Biol 270: 574–586PubMedCrossRefGoogle Scholar
  101. Kaneko K, Zulianello L, Scott M, Cooper CM, Wallace AC, James TL, Cohen FE, Prusiner SB (1997c) Evidence for protein X binding to a discontinuous epitope on the cellular prion protein during scrapie prion propagation. Proc Natl Acad Sci USA 94: 10069–10074PubMedCrossRefGoogle Scholar
  102. Kascsak RJ, Rubenstein R, Carp RI (1991) Evidence for biological and structural diversity among scrapie strains. In: Chesebro B (eds) Transmissible Spongiform Encephalopathies: Scrapie, BSE and Related Human Disorders. Springer Verlag, Berlin, Heidelberg, pp 139–152Google Scholar
  103. Kascsak RJ, Rubenstein R, Merz PA, Carp RI, Robakis NK, Wisniewski HM, Diringer H (1986) Immunological comparison of scrapie-associated fibrils isolated from animals infected with four different scrapie strains. J Virol 59: 676–683PubMedGoogle Scholar
  104. Kascsak RJ, Rubenstein R, Merz PA, Carp RI, Wisniewski HM, Diringer H (1985) Biochemical differences among scrapie-associated fibrils support the biological diversity of scrapie agents. J Gen Virol 66 (Pt 8): 1715–1722PubMedCrossRefGoogle Scholar
  105. Knaus KJ, Morillas M, Swietnicki W, Malone M, Surewicz WK, Yee VC (2001) Crystal structure of the human prion protein reveals a mechanism for oligomerization. Nat Struct Biol 8: 770–774PubMedCrossRefGoogle Scholar
  106. Kocisko DA, Come JH, Priola SA, Chesebro B, Raymond GJ, Lansbury PT, Caughey B (1994) Cell-free formation of protease-resistant prion protein. Nature 370: 471474Google Scholar
  107. Kocisko DA, Lansbury PT, Jr., Caughey B (1996) Partial unfolding and refolding of scrapie-associated prion protein: evidence for a critical 16-kDa C-terminal domain. Biochemistry 35: 13434–13442PubMedCrossRefGoogle Scholar
  108. Kocisko DA, Priola SA, Raymond GJ, Chesebro B, Lansbury PT, Jr., Caughey B (1995) Species specificity in the cell-free conversion of prion protein to protease-resistant forms: a model for the scrapie species barrier. Proc Natl Acad Sci USA 92: 3923–3927PubMedCrossRefGoogle Scholar
  109. Korth C, Kaneko K, Prusiner SB (2000) Expression of unglycosylated mutated prion protein facilitates PrP(Sc) formation in neuroblastoma cells infected with different prion strains. J Gen Virol 81: 2555–2563PubMedGoogle Scholar
  110. Kryndushkin DS, Smirnov VN, Ter Avanesyan MD, Kushnirov VV (2002) Increased expression of Hsp40 chaperones, transcriptional factors, and ribosomal protein RppO can cure yeast prions. J Biol Chem 277: 23702–23708PubMedCrossRefGoogle Scholar
  111. Kuwahara C, Takeuchi AM, Nishimura T, Haraguchi K, Kubosaki A, Matsumoto Y, Saeki K, Matsumoto Y, Yokoyama T, Itohara S, Onodera T (1999) Prions prevent neuronal cell-line death. Nature 400: 225–226PubMedCrossRefGoogle Scholar
  112. Lansbury PT, Jr., Caughey B (1995) The chemistry of scrapie infection: implications of the `ice 9’ metaphor. Chem Biol 2: 1–5PubMedCrossRefGoogle Scholar
  113. Lawson VA, Priola SA, Wehrly K, Chesebro B (2001) N-terminal truncation of prion protein affects both formation and conformation of abnormal protease-resistant prion protein generated in vitro. J Biol Chem 276: 35265–35271PubMedCrossRefGoogle Scholar
  114. Li R, Liu D, Zanusso G, Liu T, Fayen JD, Huang JH, Petersen RB, Gambetti P, Sy MS (2001) The expression and potential function of cellular prion protein in human lymphocytes. Cell Immunol 207: 49–58PubMedCrossRefGoogle Scholar
  115. Liu H, Farr-Jones S, Ulyanov NB, Llinas M, Marqusee S, Groth D, Cohen FE, Prusiner SB, James TL (1999) Solution structure of Syrian hamster prion protein rPrP(90231). Biochemistry 38: 5362–5377PubMedCrossRefGoogle Scholar
  116. Locht C, Chesebro B, Race R, Keith JM (1986) Molecular cloning and complete sequence of prion protein cDNA from mouse brain infected with the scrapie agent. Proc Natl Acad Sci USA 83: 6372–6376PubMedCrossRefGoogle Scholar
  117. Lucassen R, Nishina K, Supattapone S (2003) In vitro amplification of protease-resistant prion protein requires free sulfhydryl groups. Biochemistry 42:4127–4135 Ma J, Lindquist S (2002) Conversion of PrP to a self-perpetuating PrPSc-like conformation in the cytosol. Science 298: 1785–1788Google Scholar
  118. Marella M, Lehmann S, Grassi J, Chabry J (2002) Filipin prevents pathological prion protein accumulation by reducing endocytosis and inducing cellular PrP release. J Biol Chem 277: 25457–25464PubMedCrossRefGoogle Scholar
  119. Masel J, Jansen VA, Nowak MA (1999) Quantifying the kinetic parameters of prion replication. Biophys Chem 77: 139–152PubMedCrossRefGoogle Scholar
  120. Maxson L, Wong C, Herrmann LM, Caughey B, and Baron GS (2003) A solid-phase assay for identification of modulators of prion protein interactions. Anal Biochem (in press)Google Scholar
  121. McKenzie D, Bartz J, Mirwald J, Olander D, Marsh R, Aiken J (1998) Reversibility of scrapie inactivation is enhanced by copper. J Biol Chem 273: 25545–25547PubMedCrossRefGoogle Scholar
  122. McKinley MP, Meyer RK, Kenaga L, Rahbar F, Cotter R, Serban A, Prusiner SB (1991) Scrapie prion rod formation in vitro requires both detergent extraction and limited proteolysis. J Virol 65: 1340–1351PubMedGoogle Scholar
  123. Merz PA, Somerville RA, Wisniewski HM, Iqbal K (1981) Abnormal fibrils from scrapie-infected brain. Acta Neuropathol (Berl) 54: 63–74CrossRefGoogle Scholar
  124. Miller MW, Williams ES, McCarty CW, Spraker TR, Kreeger TJ, Larsen CT, Thorne ET (2000) Epizootiology of chronic wasting disease in free-ranging cervids in Colorado and Wyoming. J Wildl Dis 36: 676–690PubMedGoogle Scholar
  125. Monari L, Chen SG, Brown P, Parchi P, Petersen RB, Mikol J, Gray F, Cortelli P, Montagna P, Ghetti B,. (1994) Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism. Proc Natl Acad Sci USA 91: 2839–2842PubMedCrossRefGoogle Scholar
  126. Morillas M, Swietnicki W, Gambetti P, Surewicz WK (1999) Membrane environment alters the conformational structure of the recombinant human prion protein. J Biol Chem 274: 36859–36865PubMedCrossRefGoogle Scholar
  127. Moriyama H, Edskes HK, Wickner RB (2000) IURE3] prion propagation in Saccharomyces cerevisiae: requirement for chaperone Hsp104 and curing by overexpressed chaperone Ydjlp. Mol Cell Biol 20: 8916–8922PubMedCrossRefGoogle Scholar
  128. Morrissey MP, Shakhnovich EI (1999) Evidence for the role of PrP(C) helix 1 in the hydrophilic seeding of prion aggregates. Proc Natl Acad Sci USA 96: 11293–11298PubMedCrossRefGoogle Scholar
  129. Mouillet-Richard S, Ermonval M, Chebassier C, Laplanche JL, Lehmann S, Launay JM, Kellermann 0 (2000) Signal transduction through prion protein. Science 289: 1925–1928Google Scholar
  130. Muramoto T, Scott M, Cohen FE, Prusiner SB (1996) Recombinant scrapie-like prion protein of 106 amino acids is soluble. Proc Natl Acad Sci USA 93: 15457–15462PubMedCrossRefGoogle Scholar
  131. Nguyen JT, Inouye H, Baldwin MA, Fletterick RJ, Cohen FE, Prusiner SB, Kirschner DA (1995) X-ray diffraction of scrapie prion rods and PrP peptides. J Mol Biol 252: 412–422PubMedCrossRefGoogle Scholar
  132. O’Rourke KI, Besser TE, Miller MW, Cline TF, Spraker TR, Jenny AL, Wild MA, Zebarth GL, Williams ES (1999) PrP genotypes of captive and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease. J Gen Virol 80 (Pt 10): 2765–2769PubMedGoogle Scholar
  133. Oesch B, Jensen M, Nilsson P, Fogh J (1994) Properties of the scrapie prion protein: quantitative analysis of protease resistance. Biochemistry 33: 5926–5931PubMedCrossRefGoogle Scholar
  134. Oesch B, Westaway D, Walchli M, McKinley MP, Kent SB, Aebersold R, Barry RA, Tempst P, Teplow DB, Hood LE (1985) A cellular gene encodes scrapie PrP 27–30 protein. Cell 40: 735–746PubMedCrossRefGoogle Scholar
  135. Paitel E, Alves dC, Vilette D, Grassi J, Checler F (2002) Overexpression of PrPc triggers caspase 3 activation: potentiation by proteasome inhibitors and blockade by anti-PrP antibodies. J Neurochem 83: 1208–1214PubMedCrossRefGoogle Scholar
  136. Paitel E, Fahraeus R, Checler F (2003) Cellular prion protein sensitizes neurons to apoptotic stimuli through Mdm2-regulated and p53-dependent caspase 3-like activation. J Biol Chem 278: 10061–10066PubMedCrossRefGoogle Scholar
  137. Palmer MS, Dryden AJ, Hughes JT, Collinge J (1991) Homozygous prion protein gen- otype predisposes to sporadic Creutzfeldt-Jakob disease. Nature 352: 340–342PubMedCrossRefGoogle Scholar
  138. Pan KM, Baldwin M, Nguyen J, Gasset M, Serban A, Groth D, Mehlhorn I, Huang Z, Fletterick RJ, Cohen FE (1993) Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci USA 90: 10962–10966PubMedCrossRefGoogle Scholar
  139. Parchi P, Capellari S, Chen SG, Petersen RB, Gambetti P, Kopp N, Brown P, Kitamoto T, Tateishi J, Giese A, Kretzschmar H (1997) Typing prion isoforms. Nature 386: 232–234PubMedCrossRefGoogle Scholar
  140. Parizek P, Roeckl C, Weber J, Flechsig E, Aguzzi A, Raeber AJ (2001) Similar turnover and shedding of the cellular prion protein in primary lymphoid and neuronal cells. J Biol Chem 276: 44627–44632PubMedCrossRefGoogle Scholar
  141. Patino MM, Liu JJ, Glover JR, Lindquist S (1996) Support for the prion hypothesis for inheritance of a phenotypic trait in yeast. Science 273: 622–626PubMedCrossRefGoogle Scholar
  142. Pauly PC, Harris DA (1998) Copper stimulates endocytosis of the prion protein. J Biol Chem 273: 33107–33110PubMedCrossRefGoogle Scholar
  143. Peretz D, Scott MR, Groth D, Williamson RA, Burton DR, Cohen FE, Prusiner SB (2001a) Strain-specified relative conformational stability of the scrapie prion protein. Protein Sci 10: 854–863PubMedCrossRefGoogle Scholar
  144. Peretz D, Williamson RA, Kaneko K, Vergara J, Leclerc E, Schmitt-Ulms G, Mehlhorn IR, Legname G, Wormald MR, Rudd PM, Dwek RA, Burton DR, Prusiner SB (2001b) Antibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature 412: 739–743PubMedCrossRefGoogle Scholar
  145. Peretz D, Williamson RA, Legname G, Matsunaga Y, Vergara J, Burton DR, DeArmond SJ, Prusiner SB, Scott MR (2002) A change in the conformation of prions accompanies the emergence of a new prion strain. Neuron 34: 921–932PubMedCrossRefGoogle Scholar
  146. Post K, Pitschke M, Schafer O, Wille H, Appel TR, Kirsch D, Mehlhorn I, Serban H, Prusiner SB, Riesner D (1998) Rapid acquisition of beta-sheet structure in the prion protein prior to multimer formation. Biol Chem 379: 1307–1317PubMedCrossRefGoogle Scholar
  147. Priola SA (2001) Prion protein diversity and disease in the transmissible spongiform encephalopathies. Adv Protein Chem 57: 1–27PubMedCrossRefGoogle Scholar
  148. Priola SA, Caughey B, Race RE, Chesebro B (1994) Heterologous PrP molecules interfere with accumulation of protease-resistant PrP in scrapie-infected murine neuroblastoma cells. J Virol 68: 4873–4878PubMedGoogle Scholar
  149. Priola SA, Chabry J, Chan K (2001) Efficient conversion of normal prion protein (PrP) by abnormal hamster PrP is determined by homology at amino acid residue 155. J Virol 75: 4673–4680PubMedCrossRefGoogle Scholar
  150. Priola SA, Chesebro B (1995) A single hamster PrP amino acid blocks conversion to protease-resistant PrP in scrapie-infected mouse neuroblastoma cells. J Virol 69: 7754–7758PubMedGoogle Scholar
  151. Prusiner SB (1991) Molecular biology of prion diseases. Science 252:1515–1522 Prusiner SB (1998) Prions. Proc Natl Acad Sci USA 95: 13363–13383CrossRefGoogle Scholar
  152. Prusiner SB, Groth D, Serban A, Stahl N, Gabizon R (1993) Attempts to restore scrapie prion infectivity after exposure to protein denaturants. Proc Natl Acad Sci USA 90: 2793–2797PubMedCrossRefGoogle Scholar
  153. Prusiner SB, McKinley MP, Bowman KA, Bolton DC, Bendheim PE, Groth DF, Glenner GG (1983) Scrapie prions aggregate to form amyloid-like birefringent rods. Cell 35: 349–358PubMedCrossRefGoogle Scholar
  154. Prusiner SB, Scott M, Foster D, Pan KM, Groth D, Mirenda C, Torchia M, Yang SL, Serban D, Carlson GA (1990) Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63: 673–686PubMedCrossRefGoogle Scholar
  155. Race R, Jenny A, Sutton D (1998) Scrapie infectivity and proteinase K-resistant prion protein in sheep placenta, brain, spleen, and lymph node: implications for transmission and antemortem diagnosis. J Infect Dis 178: 949–953PubMedCrossRefGoogle Scholar
  156. Race RE, Raines A, Baron TG, Miller MW, Jenny A, Williams ES (2002) Comparison of abnormal prion protein glycoform patterns from transmissible spongiform encephalopathy agent-infected deer, elk, sheep, and cattle. J Virol 76: 12365–12368PubMedCrossRefGoogle Scholar
  157. Raymond GJ, Bossers A, Raymond LD, O’Rourke KI, McHolland LE, Bryant PK, III, Miller MW, Williams ES, Smits M, Caughey B (2000) Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease. EMBO J 19: 4425–4430PubMedCrossRefGoogle Scholar
  158. Raymond GJ, Hope J, Kocisko DA, Priola SA, Raymond LD, Bossers A, Ironside J, Will RG, Chen SG, Petersen RB, Gambetti P, Rubenstein R, Smits MA, Lansbury PT, Jr., Caughey B (1997) Molecular assessment of the potential transmissibilities of BSE and scrapie to humans. Nature 388: 285–288PubMedCrossRefGoogle Scholar
  159. Rieger R, Edenhofer F, Lasmezas CI, Weiss S (1997) The human 37-kDa laminin receptor precursor interacts with the prion protein in eukaryotic cells. Nat Med 3: 1383–1388PubMedCrossRefGoogle Scholar
  160. Riek R, Hornemann S, Wider G, Billeter M, Glockshuber R, Wuthrich K (1996) NMR structure of the mouse prion protein domain PrP(121–321). Nature 382: 180–182PubMedCrossRefGoogle Scholar
  161. Riek R, Hornemann S, Wider G, Glockshuber R, Wuthrich K (1997) NMR characterization of the full-length recombinant murine prion protein, mPrP(23–231). FEBS Lett 413: 282–288PubMedCrossRefGoogle Scholar
  162. Riesner D, Kellings K, Post K, Wille H, Serban H, Groth D, Baldwin MA, Prusiner SB (1996) Disruption of prion rods generates 10-nm spherical particles having high alpha-helical content and lacking scrapie infectivity. J Virol 70: 1714–1722PubMedGoogle Scholar
  163. Rogers M, Yehiely F, Scott M, Prusiner SB (1993) Conversion of truncated and elongated prion proteins into the scrapie isoform in cultured cells. Proc Natl Acad Sci USA 90: 3182–3186PubMedCrossRefGoogle Scholar
  164. Rubenstein R, Gray PC, Wehlburg CM, Wagner JS, Tisone GC (1998) Detection and discrimination of PrPSc by multi-spectral ultraviolet fluorescence. Biochem Biophys Res Commun 246: 100–106PubMedCrossRefGoogle Scholar
  165. Rudd PM, Endo T, Colominas C, Groth D, Wheeler SF, Harvey DJ, Wormald MR, Serban H, Prusiner SB, Kobata A, Dwek RA (1999) Glycosylation differences between the normal and pathogenic prion protein isoforms. Proc Natl Acad Sci USA 96: 13044–13049PubMedCrossRefGoogle Scholar
  166. Rydh A, Suhr O, Hietala SO, Ahlstrom KR, Pepys MB, Hawkins PN (1998) Serum amyloid P component scintigraphy in familial amyloid polyneuropathy: regression of visceral amyloid following liver transplantation. Eur J Nucl Med 25: 709–713PubMedCrossRefGoogle Scholar
  167. Saborio GP, Permanne B, Soto C (2001) Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411: 810–813PubMedCrossRefGoogle Scholar
  168. Saborio GP, Soto C, Kascsak RJ, Levy E, Kascsak R, Harris DA, Frangione B (1999) Cell-lysate conversion of prion protein into its protease-resistant isoform suggests the participation of a cellular chaperone. Biochem Biophys Res Commun 258: 470–475PubMedCrossRefGoogle Scholar
  169. Safar J, Roller PP, Gajdusek DC, Gibbs CJ, Jr. (1993a) Conformational transitions, dissociation, and unfolding of scrapie amyloid (prion) protein. J Biol Chem 268: 20276–20284PubMedGoogle Scholar
  170. Safar J, Roller PP, Gajdusek DC, Gibbs CJ, Jr. (1993b) Thermal stability and conformational transitions of scrapie amyloid (prion) protein correlate with infectivity. Protein Sci 2: 2206–2216PubMedCrossRefGoogle Scholar
  171. Safar J, Roller PP, Gajdusek DC, Gibbs CJ, Jr. (1994) Scrapie amyloid (prion) protein has the conformational characteristics of an aggregated molten globule folding intermediate. Biochemistry 33: 8375–8383PubMedCrossRefGoogle Scholar
  172. Safar J, Wille H, Itri V, Groth D, Serban H, Torchia M, Cohen FE, Prusiner SB (1998) Eight prion strains have PrP(Sc) molecules with different conformations. Nat Med 4: 1157–1165PubMedCrossRefGoogle Scholar
  173. Safar JG, Scott M, Monaghan J, Deering C, Didorenko S, Vergara J, Ball H, Legname G, Leclerc E, Solforosi L, Serban H, Groth D, Burton DR, Prusiner SB, Williamson RA (2002) Measuring prions causing bovine spongiform encephalopathy or chronic wasting disease by immunoassays and transgenic mice. Nat Biotechnol 20: 1147–1150PubMedCrossRefGoogle Scholar
  174. Sanghera N, Pinheiro TJ (2002) Binding of prion protein to lipid membranes and implications for prion conversion. J Mol Biol 315: 1241–1256PubMedCrossRefGoogle Scholar
  175. Scott MR, Kohler R, Foster D, Prusiner SB (1992) Chimeric prion protein expression in cultured cells and transgenic mice. Protein Sci 1: 986–997PubMedCrossRefGoogle Scholar
  176. Shaked GM, Fridlander G, Meiner Z, Taraboulos A, Gabizon R (1999) Protease-resistant and detergent-insoluble prion protein is not necessarily associated with prion infectivity. J Biol Chem 274: 17981–17986PubMedCrossRefGoogle Scholar
  177. Shaked GM, Meiner Z, Avraham I, Taraboulos A, Gabizon R (200la) Reconstitution of prion infectivity from solubilized protease-resistant PrP and nonprotein components of prion rods. J Biol Chem 276: 14324–14328Google Scholar
  178. Shaked GM, Shaked Y, Kariv-Inbal Z, Halimi M, Avraham I, Gabizon R (2001b) A protease-resistant prion protein isoform is present in urine of animals and humans affected with prion diseases. J Biol Chem 276: 31479–31482PubMedCrossRefGoogle Scholar
  179. Shyng SL, Heuser JE, Harris DA (1994) A glycolipid-anchored prion protein is endocytosed via clathrin-coated pits. J Cell Biol 125: 1239–1250PubMedCrossRefGoogle Scholar
  180. Shyng SL, Huber MT, Harris DA (1993) A prion protein cycles between the cell surface and an endocytic compartment in cultured neuroblastoma cells. J Biol Chem 268: 15922–15928PubMedGoogle Scholar
  181. Shyng SL, Lehmann S, Moulder KL, Harris DA (1995a) Sulfated glycans stimulate endocytosis of the cellular isoform of the prion protein, PrPC, in cultured cells. J Biol Chem 270: 30221–30229Google Scholar
  182. Shyng SL, Moulder KL, Lesko A, Harris DA (1995b) The N-terminal domain of a glycolipid-anchored prion protein is essential for its endocytosis via clathrin-coated pits. J Biol Chem 270: 14793–14800PubMedCrossRefGoogle Scholar
  183. Sigurdsson EM, Permanne B, Soto C, Wisniewski T, Frangione B (2000) In vivo reversal of amyloid-beta lesions in rat brain. J Neuropathol Exp Neurol 59: 11–17PubMedGoogle Scholar
  184. Somerville RA, Chong A, Mulqueen OU, Birkett CR, Wood SC, Hope J (1997) Biochemical typing of scrapie strains. Nature 386: 564PubMedCrossRefGoogle Scholar
  185. Somerville RA, Millson GC, Kimberlin RH (1980) Sensitivity of scrapie infectivity to detergents and 2-mercaptoethanol. Intervirology 13: 126–129PubMedCrossRefGoogle Scholar
  186. Somerville RA, Ritchie LA (1990) Differential glycosylation of the protein (PrP) forming scrapie-associated fibrils. J Gen Virol 71 (Pt 4): 833–839PubMedCrossRefGoogle Scholar
  187. Somerville RA, Ritchie LA, Gibson PH (1989) Structural and biochemical evidence that scrapie-associated fibrils assemble in vivo. J Gen Virol 70 (Pt 1): 25–35PubMedCrossRefGoogle Scholar
  188. Soto C, Kascsak RJ, Saborio GP, Aucouturier P, Wisniewski T, Prelli F, Kascsak R, Mendez E, Harris DA, Ironside J, Tagliavini F, Carp RI, Frangione B (2000) Reversion of prion protein conformational changes by synthetic beta-sheet breaker peptides. Lancet 355: 192–197PubMedCrossRefGoogle Scholar
  189. Speare JO, Rush TS, III, Bloom ME, Caughey B (2003) The role of helix 1 aspartates and salt bridges in the stability and conversion of prion protein. J Biol Chem 278: 12522–12529PubMedCrossRefGoogle Scholar
  190. Spielhaupter C, Schatzl HM (2001) PrPC directly interacts with proteins involved in signaling pathways. J Biol Chem 276: 44604–44612PubMedCrossRefGoogle Scholar
  191. Stahl N, Baldwin MA, Burlingame AL, Prusiner SB (1990a) Identification of glycoinositol phospholipid linked and truncated forms of the scrapie prion protein. Biochemistry 29: 8879–8884PubMedCrossRefGoogle Scholar
  192. Stahl N, Borchelt DR, Hsiao K, Prusiner SB (1987) Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell 51: 229–240PubMedCrossRefGoogle Scholar
  193. Stahl N, Borchelt DR, Prusiner SB (1990b) Differential release of cellular and scrapie prion proteins from cellular membranes by phosphatidylinositol-specific phospholipase C. Biochemistry 29: 5405–5412PubMedCrossRefGoogle Scholar
  194. Stimson E, Hope J, Chong A, Burlingame AL (1999) Site-specific characterization of the N-linked glycans of murine prion protein by high-performance liquid chromatography/electrospray mass spectrometry and exoglycosidase digestions. Biochemistry 38: 4885–4895PubMedCrossRefGoogle Scholar
  195. Sunyach C, Jen A, Deng J, Fitzgerald KT, Frobert Y, Grassi J, McCaffrey MW, Morris R (2003) The mechanism of internalisation of glycosylphosphatidylinositol-anchored prion protein. EMBO J 22: 3591–3601PubMedCrossRefGoogle Scholar
  196. Supattapone S, Bosque P, Muramoto T, Wille H, Aagaard C, Peretz D, Nguyen HO, Heinrich C, Torchia M, Safar J, Cohen FE, DeArmond SJ, Prusiner SB, Scott M (1999a) Prion protein of 106 residues creates an artifical transmission barrier for prion replication in transgenic mice. Cell 96: 869–878PubMedCrossRefGoogle Scholar
  197. Supattapone S, Nguyen HO, Cohen FE, Prusiner SB, Scott MR (1999b) Elimination of prions by branched polyamines and implications for therapeutics. Proc Natl Acad Sci USA 96: 14529–14534PubMedCrossRefGoogle Scholar
  198. Supattapone S, Wille H, Uyechi L, Safar J, Tremblay P, Szoka FC, Cohen FE, Prusiner SB, Scott MR (2001) Branched polyamines cure prion-infected neuroblastoma cells. J Virol 75: 3453–3461PubMedCrossRefGoogle Scholar
  199. Swietnicki W, Petersen R, Gambetti P, Surewicz WK (1997) pH-dependent stability and conformation of the recombinant human prion protein PrP(90–231). J Biol Chem 272: 27517–27520Google Scholar
  200. Tagliavini F, Prelli F, Porro M, Rossi G, Giaccone G, Farlow MR, Dlouhy SR, Ghetti B, Bugiani O, Frangione B (1994) Amyloid fibrils in Gerstmann-StrausslerScheinker disease ( Indiana and Swedish kindreds) express only PrP peptides encoded by the mutant allele. Cell 79: 695–703Google Scholar
  201. Taraboulos A, Scott M, Semenov A, Avrahami D, Laszlo L, Prusiner SB, Avraham D (1995) Cholesterol depletion and modification of COOH-terminal targeting sequence of the prion protein inhibit formation of the scrapie isoform. J Cell Biol 129: 121–132PubMedCrossRefGoogle Scholar
  202. Tatzelt J, Prusiner SB, Welch W] (1996) Chemical chaperones interfere with the formation of scrapie prion protein. EMBO J 15: 6363–6373PubMedGoogle Scholar
  203. Telling GC, Parchi P, DeArmond SJ, Cortelli P, Montagna P, Gabizon R, Mastrianni J, Lugaresi E, Gambetti P, Prusiner SB (1996) Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity. Science 274: 2079–2082PubMedCrossRefGoogle Scholar
  204. Thackray AM, Knight R, Haswell SJ, Bujdoso R, Brown DR (2002) Metal imbalance and compromised antioxidant function are early changes in prion disease. Biochem J 362: 253–258PubMedCrossRefGoogle Scholar
  205. Tobler I, Deboer T, Fischer M (1997) Sleep and sleep regulation in normal and prion protein-deficient mice. J Neurosci 17: 1869–1879PubMedGoogle Scholar
  206. Tobler I, Gaus SE, Deboer T, Achermann P, Fischer M, Rulicke T, Moser M, Oesch B, McBride PA, Manson JC (1996) Altered circadian activity rhythms and sleep in mice devoid of prion protein. Nature 380: 639–642PubMedCrossRefGoogle Scholar
  207. Tuo W, O’Rourke KI, Zhuang D, Cheevers WP, Spraker TR, Knowles DP (2002) Pregnancy status and fetal prion genetics determine PrPSc accumulation in placentomes of scrapie-infected sheep. Proc Natl Acad Sci USA 99: 6310–6315PubMedCrossRefGoogle Scholar
  208. Turk E, Teplow DB, Hood LE, Prusiner SB (1988) Purification and properties of the cellular and scrapie hamster prion proteins. Eur J Biochem 176: 21–30PubMedCrossRefGoogle Scholar
  209. Tzaban S, Friedlander G, Schonberger O, Horonchik L, Yedidia Y, Shaked G, Gabizon R, Taraboulos A (2002) Protease-sensitive scrapie prion protein in aggregates of heterogeneous sizes. Biochemistry 41: 12868–12875PubMedCrossRefGoogle Scholar
  210. Viles JH, Cohen FE, Prusiner SB, Goodin DB, Wright PE, Dyson HJ (1999) Copper binding to the prion protein: structural implications of four identical cooperative binding sites. Proc Natl Acad Sci USA 96: 2042–2047PubMedCrossRefGoogle Scholar
  211. Vorberg I, Chan K, Priola SA (2001) Deletion of beta-strand and alpha-helix secondary structure in normal prion protein inhibits formation of its protease-resistant isoform. J Virol 75: 10024–10032PubMedCrossRefGoogle Scholar
  212. Vorberg I, Priola SA (2002) Molecular basis of scrapie strain glycoform variation. J Biol Chem 277: 36775–36781PubMedCrossRefGoogle Scholar
  213. Wadsworth JD, Hill AF, Joiner S, Jackson GS, Clarke AR, Collinge J (1999) Strain-specific prion-protein conformation determined by metal ions. Nat Cell Biol 1: 55–59PubMedCrossRefGoogle Scholar
  214. Waggoner DJ, Drisaldi B, Bartnikas TB, Casareno RL, Prohaska JR, Gitlin JD, Harris DA (2000) Brain copper content and cuproenzyme activity do not vary with prion protein expression level. J Biol Chem 275: 7455–7458PubMedCrossRefGoogle Scholar
  215. Weissmann C (1991) A `unified theory’ of prion propagation. Nature 352:679–683 Weissmann C (1999) Molecular genetics of transmissible spongiform encephalopathies. J Biol Chem 274: 3–6CrossRefGoogle Scholar
  216. Welker E, Raymond LD, Scheraga HA, Caughey B (2002) Intramolecular versus intermolecular disulfide bonds in prion proteins. J Biol Chem 277: 33477–33481PubMedCrossRefGoogle Scholar
  217. Welker E, Wedemeyer WJ, Scheraga HA (2001) A role for intermolecular disulfide bonds in prion diseases? Proc Natl Acad Sci USA 98: 4334–4336PubMedCrossRefGoogle Scholar
  218. White AR, Enever P, Tayebi M, Mushens R, Linehan J, Brandner S, Anstee D, Collinge J, Hawke S (2003) Monoclonal antibodies inhibit prion replication and delay the development of prion disease. Nature 422: 80–83PubMedCrossRefGoogle Scholar
  219. Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A, Smith PG (1996) A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347: 921–925PubMedCrossRefGoogle Scholar
  220. Wille H, Michelitsch MD, Guenebaut V, Supattapone S, Serban A, Cohen FE, Agard DA, Prusiner SB (2002) Structural studies of the scrapie prion protein by electron crystallography. Proc Natl Acad Sci USA 99: 3563–3568PubMedCrossRefGoogle Scholar
  221. Wille H, Prusiner SB (1999) Ultrastructural studies on scrapie prion protein crystals obtained from reverse micellar solutions. Biophys J 76: 1048–1062PubMedCrossRefGoogle Scholar
  222. Williams ES, Miller MW (2002) Chronic wasting disease in deer and elk in North America. Rev Sci Tech 21: 305–316PubMedGoogle Scholar
  223. Winklhofer KF, Tatzelt J (2000) Cationic lipopolyamines induce degradation of PrPSc in scrapie-infected mouse neuroblastoma cells. Biol Chem 381: 463–469PubMedCrossRefGoogle Scholar
  224. Wong BS, Chen SG, Colucci M, Xie Z, Pan T, Liu T, Li R, Gambetti P, Sy MS, Brown DR (2001a) Aberrant metal binding by prion protein in human prion disease. J Neurochem 78: 1400–1408PubMedCrossRefGoogle Scholar
  225. Wong C, Xiong LW, Horiuchi M, Raymond L, Wehrly K, Chesebro B, Caughey B (2001b) Sulfated glycans and elevated temperature stimulate PrPSc-dependent cell-free formation of protease-resistant prion protein. EMBO J 20: 377–386PubMedCrossRefGoogle Scholar
  226. Wuthrich K, Riek R (2001) Three-dimensional structures of prion proteins. Adv Protein Chem 57: 55–82PubMedCrossRefGoogle Scholar
  227. Xiong LW, Raymond LD, Hayes SF, Raymond GJ, Caughey B (2001) Conformational change, aggregation and fibril formation induced by detergent treatments of cellular prion protein. J Neurochem 79: 669–678PubMedCrossRefGoogle Scholar
  228. Zanata SM, Lopes MH, Mercadante AF, Hajj GN, Chiarini LB, Nomizo R, Freitas AR, Cabral AL, Lee KS, Juliano MA, de Oliveira E, Jachieri SG, Burlingame A, Huang L, Linden R, Brentani RR, Martins VR (2002) Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection. EMBO J 21: 33073316Google Scholar
  229. Zeidler M, Stewart G, Cousens SN, Estibeiro K, Will RG (1997) Codon 129 genotype and new variant CJD. Lancet 350: 668PubMedCrossRefGoogle Scholar
  230. Zhang H, Stockel J, Mehlhorn I, Groth D, Baldwin MA, Prusiner SB, James TL, Cohen FE (1997) Physical studies of conformational plasticity in a recombinant prion protein. Biochemistry 36: 3543–3553PubMedCrossRefGoogle Scholar
  231. Zou WQ, Cashman NR (2002) Acidic pH and detergents enhance in vitro conversion of human brain PrPC to a PrPSc-like form. J Biol Chem 277: 43942–43947PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • J. R. Silveira
    • 1
  • B. Caughey
    • 1
  • G. S. Baron
    • 1
  1. 1.Laboratory of Persistent Viral Diseases, NIAID, NIH, Rocky Mountain LaboratoriesHamiltonUSA

Personalised recommendations