Prions and the Transmissible Spongiform Encephalopathies

  • Richard C. Wiggins


The purpose of this chapter is to highlight the prion protein, which is expressed in a wide range of tissues and most likely has a variety of important cellular functions, and its role in producing the neurodegenerative diseases known as the transmissible spongiform encephalopathies (TSEs). The protein is a normal cellular protein; however, it possess a unique property, so that when the normal α-helix-rich conformation is converted to a misfolded, β-sheet-rich conformation, the resultant particulate protein is infectious and produces a TSE, whose clinical features vary somewhat depending on the species (e.g., cow, sheep, human, etc.). The basic mechanism of infectivity remains mostly unknown, but it seems to be correctly thought of as a slowly progressing type of chain reaction. This model is often described as “recruitment and conversion.” The resultant TSEs are akin to other neurodegenerative diseases in that the TSEs are extraordinarily slow progressing diseases in humans and animals. In humans, after presymptomatic periods of as long as several decades, they are fatal and incurable. The unique primary and higher-order structure of the prion proteins of each species imparts a unique character to the TSEs of each species. Additionally, allelic variation at key structural sites appears to impart a unique character to the resultant disease. Variances in the character of disease resultant from these structural differences appear to account for the concept of “prion strains”.

While most of the TSEs are relatively rare, a recent epidemic (1986–2000) of the prion disease known as bovine spongiform encephalopathy (BSE), or mad cow, thrust the TSEs into the public awareness, especially since the consumption of beef contaminated with infectious central nervous system (CNS) tissue seems to have transmitted the mad cow disease to humans (Will et al., 1996; Collinge et al., 1996; Bruce et al., 1997; Will et al., 1999). The original event that triggered the BSE epidemic will not likely ever be known with certainty; however, it is generally thought to be from the introduction in 1926 in the United Kingdom (BSE Inquiry, 2000) of cattle feed containing offals (including brain and spinal cord) and ­mammalian meat and bone meal (MBM) animal by-products. It is thought that at some point the process was contaminated with infectious prion material, possibly sheep offals infected with scrapie, which precipitated the mad cow epidemic (BSE Inquiry, 2000). Scrapie disease in sheep is also a TSE, and it has been epidemic in sheep in the United Kingdom for 200 years. The removal of offals and mammalian meat and bone meal additives appeared to end the epidemic, which supports the offal—scrapie theory for the origin of the epidemic; however, there are other theories (Chesebro, 2004). There are also indications that the epidemic may have featured multiple strains of the prion protein (Capobianco et al., 2007). The transmitted disease in humans is known as a new variant of the Creutzfledt–Jacob disease (vCJD). The mad cow outbreak peaked in 1992 and all but disappeared in the United Kingdom by 2000. Because the incubation period for the TSEs is typically extraordinarily long, years or even decades, speculation abounds as to whether vCJD in humans has already peaked or remains dormant in the form of a future epidemic waiting to emerge (Brown, 2001).


Prion Protein Prion Disease Bovine Spongiform Encephalopathy PRNP Gene Infectious Prion 
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  1. Aguzzi, A. 2005. Prion toxicity: all sail and no anchor. Science 308: 1420–1421PubMedCrossRefGoogle Scholar
  2. Alper, T., Haig, D. A., and Clarke, M. C. 1966. The exceptionally small size of the scrapie agent. Biochem. Biophys. Res. Commun. 22: 278–284PubMedCrossRefGoogle Scholar
  3. Alper, T., Cramp, W. A., Haig, D. A., and Clarke, M. C. 1967. Does the agent of scrapie replicate without nucleic acid? Nature 214: 764–766PubMedCrossRefGoogle Scholar
  4. Angers, R. C., Browning, S. R., Seward, T. S., Sigurdson, C. J., Miller, M. W., Hoover, E. A., and Telling, G. C. 2006. Prions in skeletal muscles of deer with chronic wasting disease. Science 311: 1117PubMedCrossRefGoogle Scholar
  5. Bailey, C. H., Kandel, E. R., and Si, K. 2004. The persistence of long-term memory: a molecular approach to self-sustaining changes in learning-induced synaptic growth. Neuron 44: 49–57PubMedCrossRefGoogle Scholar
  6. Basler, K., Oesch, M., Scott, M., Westaway, D., Walchli, M., Groth, D. F., McKinley, M. P., Prusiner, S. B., and Weissmann, C. 1986. Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell 46: 417–428PubMedCrossRefGoogle Scholar
  7. Bolton, D. C., McKinley, M. P., and Prusiner, S. B. 1982. Identification of a protein that purifies with the scrapie prion. Science 218: 1309–1311PubMedCrossRefGoogle Scholar
  8. Bons, N., Mestre-Frances, N., Belli, P., Cathala, F., Gajdusek, D. C., and Brown, P. 1999. Natural and experimental oral infection of nonhuman primates by bovine spongiform encephalopathy agents. Proc. Natl. Acad. Sci. 96: 4046–4051PubMedCrossRefGoogle Scholar
  9. Brandner, S., Isenmann, S., Raeber, A., Fischer, M., Sailer, A., Kobayashi, Y., Marino, S., Weissmann, C., and Aguzzi, A. 1996. Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature 379: 339–343.PubMedCrossRefGoogle Scholar
  10. Borchelt, D. R., Scott, M., Taraboulos, A., Stahl, N., and Prusiner, S. B. 1990. Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells. J. Cell Biol. 110: 743–752PubMedCrossRefGoogle Scholar
  11. Brown, P. 2001. Bovine spongiform encephalopathy and variant Creutzfeldt — Jacob diseae. BMJ 322: 841–844PubMedCrossRefGoogle Scholar
  12. Brown, D. R (Editor). 2005. Neurodegeneration and Prion Disease. Springer, Berlin Heidelberg New YorkGoogle Scholar
  13. Brown, P. and Gajdusek, D. C. 1991. Survival of scrapie virus after 3 year’s interment. Lancet 337: 269–270PubMedCrossRefGoogle Scholar
  14. Brown, D. R., Qin, K., Herms, J. W., Madlung, A., Manson, J., Strome, R., Fraser, P. E., Kruck, T., von Bohlen, A., Schulz-Schaeffer, W., Giese, A., Westaway, D., and Kretzschmar, H. 1997. The cellular prion protein binds copper in vivo. Nature 390: 684–687PubMedCrossRefGoogle Scholar
  15. Brown, P., Will, R. G., Bradley, R., Asher, D. M., and Detwiler, L. 2001. Bovine spongiform encephalopathy and variant Creutzfeldt — Jacob disease: background, evolution, and current concerns. Emerging Infect. Dis. 7: 6–16PubMedCrossRefGoogle Scholar
  16. Brown, P., Rau, E. H., Lemieux, P., Johnson, B. K., Bacote, A. E., and Gajdusek, D. C. 2004. Infectivity studies of both ash and air emissions from simulated incineration of scrapie-contaminated tissues. Environ. Sci. Technol. 38: 6155–6160PubMedCrossRefGoogle Scholar
  17. Bruce, M. E., Will, R. G., Ironside, J. W., McConnell, I., Drummond, D., Suttie, A., McCardle, L., Chree, A., Hope, J., Birkett, C., Cousens, S., Fraser, H., and Bostock, C. J. 1997. Transmission to mice indicate tht “ new variant ” CJD is caused by BSE agent. Nature 389: 498–501PubMedCrossRefGoogle Scholar
  18. BSE Inquiry Report. 2000.
  19. Calzolai, L., Lysek, D. A., P é rez, D. A., G ü ntert, P., and W ü thrich, K. 2005. Prion protein NMR structures of chickens, turtles, and frogs. Proc. Nat. Acad. Sci. 102: 651–655PubMedCrossRefGoogle Scholar
  20. Capobianco, R., Casalone, C., Suardi, S., Mangieri, M., Miccolo, C., Limido, L., Catania, M., Rossi, G., Di Fede, G., Giaccone, G., Bruzzone, M. G., Minati, L., Corona, C., Acutis, P., Gelmetti, D., Lombardi, G., Groschup, M. H., Buschmann, A., Zanusso, G., Monaco, S., Caramelli, M., and Tagliavini, F. 2007. Conversion of the BASE prion strain into the BSE strain: The origin of BSE. PLoS Pathog. 3: e31PubMedCrossRefGoogle Scholar
  21. Carrell, R. W. 2004. Prion dormancy and disease. Science 306: 1692–1693PubMedCrossRefGoogle Scholar
  22. Castilla, J., Saα , P., Hetz, C., and Soto, C. 2005. In vitro generation of indectious scrapie prions. Cell 121: 195–206PubMedCrossRefGoogle Scholar
  23. Chesebro, B. 2004. A fresh look at BSE. Science 305:1918–1921PubMedCrossRefGoogle Scholar
  24. Chesebro, B., Trifilo, M., Race, R., Meade-White, K., Teng, C., LaCasse, R., Raymond, L., Favara, C., Baron, G., Priola, S., Caughey, B., Masliah, E., and Oldstone, M. 2005. Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science 308: 1435–1439PubMedCrossRefGoogle Scholar
  25. Collinge, J., Sidle, K. C. L., Meads, J., Ironside, J., and Hill, A. F. 1996. Molecular analysis of prion strain variation and the aetiology of a “ new variant ” CJD. Nature 383: 685–690PubMedCrossRefGoogle Scholar
  26. Come, H. H., Fraser, P. E., and Lansbury, P. T., Jr., 1993. A kinetic model for amyloid formation in the prion diseases: importance of seeding. Proc. Nat. Acad. Sci 90: 5959–5963PubMedCrossRefGoogle Scholar
  27. Cox, D. L., Pan, J., and Singh, R. R. P. 2006. A mechanism for copper inhibition of infectious prion conversion. Biophys. J. 91: L11–L13PubMedCrossRefGoogle Scholar
  28. DeArmond, S. J., Kristensson, and Bowler, R. P. 1992. PrP Sc causes nerve cell death and stimulates astrocyte proliferation: a paradox. Prog. Brain Res. 94: 437–446Google Scholar
  29. DeJoia, C., Moreaux, B., O’Connell, K., and Bessen, R. A. (2006). Prion infection of oral and nasal mucosa. J. Virol. 80: 4546–4556PubMedCrossRefGoogle Scholar
  30. Diener, T. O., McKinley, M. P., and Prusiner, S. B. 1982. Viroids and prions. Proc. Natl. Acad. Sci. 79: 5220–5224PubMedCrossRefGoogle Scholar
  31. Enserink, M. 2005. After the crisis: more questions about prions. Science 310: 1756–1758PubMedCrossRefGoogle Scholar
  32. Goldfarb, L. G., Brown, P., McCombie, W. R., Goldgaber, D., Swergold, G. D., Wills, P. R., Cervenakova, L., Baron, H., Gibbs, Jr. C. J., Gajdusek, C. 1991. Transmissible familial Creutzfeldt — Jacob disease associated with five, seven, and eight octapeptide coding repeats in the PRNP gene. Proc. Natl. Acad. Sci. 88: 10926–10930PubMedCrossRefGoogle Scholar
  33. Griffith, J. S. 1967. Self-replication and scrapie. Nature 215: 1043–1044PubMedCrossRefGoogle Scholar
  34. Halliday, S., Houston, F. and hunter, N. 2005. Expression of PrP C on cellular components of sheep blood. J. Gen. Virol. 86: 1571–1579PubMedCrossRefGoogle Scholar
  35. Harris, D. A., Falls, D. L., Johnson, F. A., and Fischbach, G. D. 1991. A prion-like protein from chicken brain copurifies with an acetylcholine-inducing activity. Proc. Natl. Acad. Sci. 88: 7664–7668PubMedCrossRefGoogle Scholar
  36. Heikenwalder, M., Zeller, N., Seeger, H., Prinz, M., Kl ö hn, P. C., Schwarz, P., Ruddle, N. H., Weissmann, C., and Aguzzi, A. 2005. Chronic lymphocytic inflammation specifies the organ trophism of prions. Science 307: 1107–1110PubMedCrossRefGoogle Scholar
  37. Heppner, F. L., Musahl, C., Arrighi, I., Klein, M. A., R ü licke, T., Oesch, B., Zinkernagel, R. M., Kalinke, U., and Aguzzi, A. 2001. Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies. Science 294: 178–182PubMedCrossRefGoogle Scholar
  38. Herrmann, L. M., Davis, W. C., Knowles, D. P., Wardrop, K. J., Sy, M. S., Gambetti, P., and O’Rourke, K. I. 2001. Cellular prion protein is expressed on peripheral blood mononuclear cells but not on platelets of normal and scrapie-infected sheep. Haematologica 86: 146–153PubMedGoogle Scholar
  39. Holada, K., Vostal, J. G., Thiesen, P. W., MacAuley, C., Gregori, L., and Rohwer, R. G. 2002. Scrapie infectivity in hamster blood is not associated with platelets. J. Virol. 76: 4649–4650PubMedCrossRefGoogle Scholar
  40. Hornshaw, M. P., McDermott, J. R., and Candy, J. M. 1995. Copper binding to the N-terminal tandem repeat regions of mammalian and avian prion protein. Biochem. biophys. Res. Commun. 207: 621–629PubMedCrossRefGoogle Scholar
  41. Jackson, G. S., Hosszu, L. L. P., Power, A., Hill, A. F., Kenney, J., Saibil, H., Craven, C. J., Waltho, J. P., Clarke, A. R., and Collinge, J. 1999. Reversible conversion of monomeric human prion protein between native and fibrilogenic conformations. Science 283: 1935–1937PubMedCrossRefGoogle Scholar
  42. Jeffrey, M., Gonz á lez, L., Espenes, A., Press, C. M., Martin, S., Chaplin, M., DAvis, L., Landsverk, T., MacAldowie, C., Eaton, S., and McGovern, G. 2006. Transportation of prion protein across the intestinal mucosa of scrapie-susceptible and scrapie-resistant sheep. J. Pathol. 209: 4–14PubMedCrossRefGoogle Scholar
  43. Johnson, C. J., Phillips, K. E., Schramm, P. T., McKenzie, D., Aiken, J. M., and Pedersen, J. A. 2006. Prions adhere to soil minerals and remain infectious. PLoS Pathog. 2: e32PubMedCrossRefGoogle Scholar
  44. Konturek, P. C., Bazela, K., Kukharskyy, V., Bauer, M., Hahn, E. G., and Schuppan, D. 2005. Helicobacter pylori upregulates prion protein expression in gastric mucosa: A possible link to prion disease. World J. Gastroenterol. 11: 7651–7656PubMedGoogle Scholar
  45. Krebs, M. R. H., Morozova-Roche, L. A., Daniel, K., Robinson, C. V., and Dobson, C. M. 2004. Observation of sequence specificity in the seeding of protein amyloid fibrils. Protein Sci. 13: 1933–1938PubMedCrossRefGoogle Scholar
  46. Kuwahara, C., Takeuchi, A. M., Nishimura, T., Haraguchi, K., Kubosaki, A., Matsumoto, Y., Saeki, K., Matsumoto, Y., Yokoyama, T., Itohara, S., and Onodera, T. 1999. Prions prevent neuronal cell-line death. Nature 400: 225–226PubMedCrossRefGoogle Scholar
  47. Lee, H. S., Brown, P., Cerven á kov á, L., Garruto, R. M., Alpers, M. P., Gajkusek, D. C., and Goldfarb, L. G. 2001. Increased susceptibility to kuru of carriers of the PRNP 129 Methionine/ Methionine genotype. J. Infect. Dis. 183: 192–196PubMedCrossRefGoogle Scholar
  48. Lee, D. C., Sakudo, A., Chi-keyong, K., Nishimura, T., Saeki, K., Matsumoto, Y., Yokoyama, T., Chen, S. G., Itohara, S., and Onodera, T. 2006. Fusion of Doppel to octapeptide repeat and N-terminal half of hydophobic region of prion protein confers resistence to serum deprivation. Microbiol. Immunol. 50: 203–209PubMedGoogle Scholar
  49. Legname, G., Baskakov, I. V., Nguyen, O. A. B., Riesner, D., Cohen, F. E., DeArmond, S. J., and Prusiner, S. B. 2004. Synthetic mammalian prions. Science 305: 673–676PubMedCrossRefGoogle Scholar
  50. Lewis, P. A., Properzi, F., Prodromidou, K., Clarke, A. R., Collinge, J., and Jackson, G. S. 2006. Removal of the glycosylphosphatidylinositol anchor from PrP cathepsin D does not reduce prion infectivity. Biochem. J. 395: 443–448PubMedCrossRefGoogle Scholar
  51. Liberski, P. P. and Ironside, J. W. 2005. Neuropathology of transmissible spongiform encephalopathies (prion disease). In, Brown, D. R (Editor). 2005. Neurodegeneration and Prion Disease. Springer, Berlin Heidelberg New York, pp. 13–48CrossRefGoogle Scholar
  52. Lundmark, K., Westermark, G. T., Nystr ö m, S., Murphy, C. L., Solomon, A., and Westermark, P. 2002. Transmissibility of systemic amyloidosis by a prion-like mechanism. Proc. Natl. Acad. Sci. 99: 6979–6984PubMedCrossRefGoogle Scholar
  53. Mallucci, G., Dickinson, A., Linehan, J., Kl ö hn, P. C., Brandner, S., and Collinge, J. 2003. Depleting neuronal PrP in Prion infection prevents disease and reverses spongiosis. Science 302: 871–874PubMedCrossRefGoogle Scholar
  54. Manuelidis, L., Yu, Z. X., Banquero, N., and Mullins, B. 2007. Cells infected with scrapie and Creutzfeldt — Jacob disease agents produce intracellular 25-nm virus-like particles. Proc. Natl. Acad. Sci. 104: 1965–1970PubMedCrossRefGoogle Scholar
  55. Mathiason, C. K., Powers, J. G., Dahmes, S. J., Osborn, D. A., Miller, K. V., Warren, R. J., Mason, G. L., Hays, S. A., Hayes-Klug, J., Seelig, D. M., Wild, M. A., Wolfe, L. L., Spraker, T. R., Miller, M. W., Sigurdson, C. J., Telling, G. C., and Hoover, E. A. 2006. Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 314: 133–136PubMedCrossRefGoogle Scholar
  56. Mead, S., Stumpf, M. P. H., Whitfield, J., Beck, J. A., Poulter, M., Campbell, T., Uphill, J. B., Goldstein, D., Alpers, M., Fisher, E. M. C., and Collinge, J. 2003. Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics. Science 300: 64–643CrossRefGoogle Scholar
  57. Meyer-Luehmann, M., Coomaraswamy, J., Bolmont, T., Kaeser, S., Schaefer, C., Kilger, E., Neuenschwander, A., Abramowski, D., Frey, P., Jaton, A. L., Vigouret, J.- M., Paganetti, P., Walsh, D. M., Mathews, P. M., Ghiso, J., Staufenbeil, M., Walker, L. C., and Jucker, M. 2006. Exogenous induction of cerebral β -amyloidogenesis is governed by agent and host. Science 313: 1781–1784PubMedCrossRefGoogle Scholar
  58. Mouillet-Richard, S., Ermonval, M., Chebassier, C., Laplanche, J. L., Lehmann, S., Launay, J. M., and Kellermann, O. 2000. Signal transduction through prion protein. Science 289: 1925–1928PubMedCrossRefGoogle Scholar
  59. Oesch, B., Westaway, D., Walchli, M., McKinley, M. P., Kent, S. B. H., Aebersold, R., Barry, R. A., Tempst, P., Teplow, D. B., Hood, L. E., Prusiner, S. B., and Weissmann, C. 1985. A cellular gene encodes scrapie Prp 27–30 protein. Cell 40: 735–746PubMedCrossRefGoogle Scholar
  60. Pankiewicz, J., Prelli, F., ManSun, S. Y., Kascsak, R. J., Kascsak, R. B., Spinner, D. S., Carp, R. I., Meeker, H. C., Sadowski, M., and Wisniewski, T. 2006. Clearance and prevention of prion infection in cell culture by anti-PrP antibodies. Eur. J. Neurosci. 23: 2635–2647PubMedCrossRefGoogle Scholar
  61. Peretz, D., Williamson, R. A., Kaneko, K., Vergara, J., Leclerc, E., Schmitt-Ulms, G., Mehlhorn, I. R., Legname, G., Wormald, M. R., Rudd, P. M., Dwek, R. A., Burton, D. R., and Prusiner, S. B. 2001. Antibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature 412: 739–743PubMedCrossRefGoogle Scholar
  62. Perini, F., Frangione, B., and Prelli, F. 1996. Prion protein release by platelets. Lancet 347: 1635–1636PubMedCrossRefGoogle Scholar
  63. Prusiner, S. B. 1982. Novel proteinaceous infectious particles cause scrapie. Science 216: 136–144PubMedCrossRefGoogle Scholar
  64. Prusiner, S. B., Gajdusekk, C., and Aplers, M. P. 1982. Kuru with incubation periods exceeding two decades. Ann. Neurol. 12: 1–9PubMedCrossRefGoogle Scholar
  65. Prusiner, S. B., Groth, D. F., Bolton, D. C., Kent, S. B., and Hood, L. E., Prusiner, S. B. 1984. Purification and structural studies of a major scrapie prion protein. Cell 38: 127–134PubMedCrossRefGoogle Scholar
  66. Re, L., Rossini, F., Re, F., Bordicchia, M., Mercanti, A., Fernandez, O. S. L., and Barocci, S. 2006. Prion protein potentiates acetylcholine release at the neuromuscular junction. Pharmacol. Res. 53: 62–68PubMedCrossRefGoogle Scholar
  67. Robertson, C., Booth, S. A., Beniac, D. R., Coulthart, M. B., Booth, T. F., and McNicol, A. 2006. Cellular prion protein is released on exosomes from activated platelets. Blood 107: 3907–3911PubMedCrossRefGoogle Scholar
  68. Saá , P., Castilla, J., and Soto, C. 2006. Presymptomatic detection of prions in blood. Science 313: 92–94PubMedCrossRefGoogle Scholar
  69. Sadowski, M. and Wisniewski, T. 2004. Vaccines for conformational disorders. Expert Rev. Vaccines 3: 279–290PubMedCrossRefGoogle Scholar
  70. Safar, J. G., Kellings, K., Serban, A., Groth, D., Cleaver, J. E., Prusiner, S. B., and Riesner, D. 2005. Search for a prion-specific nucleic acid. J. Virol. 79: 10796–10806.PubMedCrossRefGoogle Scholar
  71. Sakaguchi, S. 2005. Prion protein, prion protein-like protein and neurodegeneration. In Brown D. R. Neurodegeneration and Prion Disease, Springer, Berlin Heidelberg New York, pp. 167–193CrossRefGoogle Scholar
  72. Schoch, G., Seeger, H., Bogousslavsky, J., Tolnay, M., Janzer, R. C., Aguzzi, A., and Glatzel, M. 2006. An anlaysis of prion strains by PrP Sc profiling in sporadic Creutzfeldt — Jacob disease. PLoS Med. 3: e14 (236–244)PubMedCrossRefGoogle Scholar
  73. Seeger, H., Heikenwalder, M., Zeller, N., Kranich, J., Schwarz, P., Gaspert, A., Seifert, B., Miele, G., and Aguzzi, A. 2005. Coincident scrapie infection and nephritis lead to urinary prion excretion. Science 310: 324–326PubMedCrossRefGoogle Scholar
  74. Soto, C. 2006. Prions. The New Biology of Proteins. CRC Press, Boca Raton, USAGoogle Scholar
  75. Stahl, N., Borchelt, D. R., and Prusiner, S. B. 1990. Differential release of cellular and scrapie prion protein form cellular membranes of phosphatidylinositol specific phospholipase. Biochemistry 29: 5405–5412PubMedCrossRefGoogle Scholar
  76. Starke, R., Harrison, P., Mackie, I., Wang, G., Erusalimsky, J. D., Gale, R., Massé , J. M., Cramer, E., Pizzey, A., Biggerstaff, J., and Machin, S. 2005. The experssion of prion protein (PrP C ) in the magakaryocyte lineage. J. Thromb. Haemost. 3: 1266–1273PubMedCrossRefGoogle Scholar
  77. Steele, A. D., Emsley, J. G., Ö zdinler, P. H., lindquist, S., and Macklis, J. D. 2006. Prion protein (PrP C ) positively regulates neuroal precursor proliferation during developmental and adult mammalian neurogenesis. Proc. Natl. Acad. Sci. 103: 3416–3421PubMedCrossRefGoogle Scholar
  78. Sulforosi, L., Criado, J. R., McGavern, D. B., Wirz, S., S á nchez-Alvarez, M., Sugama, S., DeGiorgio, L. A., Volpe, B. T., Wiseman, E., Abalos, G., Masliah, E., Gilden, D., Oldstone, M. B., Conti, B., and Williamson, R. A. 2004. Cross-linking cellular prion protein triggers neuronal apoptosis in vivo. Science 303: 1514–1516CrossRefGoogle Scholar
  79. Supattapone, S., Nguyen, H. O. B., Cohen, F. E., Prusiner, S. B., and Scott, M. R. 1999. Elimination of prions by branched polyamines and implications for therapeutics. Proc. Natl. Acad. Sci. 96: 14529–14534PubMedCrossRefGoogle Scholar
  80. Supattapone, S., Wille, H., Uyechi, L., Safar, J., Tremblay, P., Szoka, F., Cohen, F. E., Prusiner, S. B., and Scott, M. R. 2001. Branched polyamines cure prion-infected neuroblastoma cells. J. Virol. 75: 3453–3461PubMedCrossRefGoogle Scholar
  81. Taylor, D. M. 1990. Inactivation of the BSE agent. Dev. Biol. Stand. 75:97–102Google Scholar
  82. Taylor, J. P., Hardy, J., and Fischbeck, K. H. 2002. Toxic proteins in neurodegenerative disease. Science 296: 1991–1995PubMedCrossRefGoogle Scholar
  83. Wadsworth, J. D. F., Asante, E. A., Desbruslais, M., Linehan, J. M., Joiner, S., Gowland, I., Welch, J., Stone, L., Lloyd, S. E., Hill, A. F., Brandner, S., and Collinge, J. 2004. Human prion protein with Valine 129 prevents expression of variant CJD phenotype. Science 306: 1793–1796PubMedCrossRefGoogle Scholar
  84. Watts, J. C., Balanchandran, A., and Westaway, D. 2006. The expanding universe of prion diseases. PLoS Pathog. 2(3): e26PubMedCrossRefGoogle Scholar
  85. Westaway, D. and Prusiner, S. B. 1986. Conservation of the cellular gene encoding scrapie prion protein. Nucleic Acids Res. 14: 2035–2044PubMedCrossRefGoogle Scholar
  86. Will, R. G., Ironside, J. W., Zeidler, M., Cousens, S. N., Estiberio, K., Alperovitch, A., Posner, S., Pocchiari, M., Hofman, A., and Smith, P. G. 1996. A new variant of Creutzfeldt — Jacob disease in the UK. Lancet 347: 921–925PubMedCrossRefGoogle Scholar
  87. Will, R. G., Cousens, S. N., Farrington, C. P., Smith, P. G., Knight, R. S. G., and Ironside, J. W. 1999. Deaths from variant Creutzfeldt — Jacob disease. Lancet 353: 979PubMedCrossRefGoogle Scholar
  88. Xie, Z., O’Rourke, K. I., Dong, Z., Jenny, A. L., Langenberg, J. A., Belay, E. D., Schonberger, L. B., Petersen, R. B., Zou, W., Kong, Q., Gambetti, P., and Chen, S. G. 2006. Chronic wasting disease of elk and deer and Creutzfeldt — Jacob disease. 2006. J. Biol. Chem. 281: 4199–4206PubMedCrossRefGoogle Scholar
  89. Zhang, C. C., Steele, A. D., Lindquist, S., and Lodish, H. F. 2006. Prion protein is expressed on long-term repopulating hematopoetic stem cells and is important to their self-renewal. Proc. Natl. Acad. Sci. 103: 2184–2189PubMedCrossRefGoogle Scholar
  90. Zobeley, E., Flechsig, E., Cozzio, A., Enari, M., and Weissman, C. 1999. Infectivity of scrapie prions bound to stainless steel surface. Mol. Med. 5: 240–243PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Richard C. Wiggins
    • 1
  1. 1.National Health and Environmental Effects Research Laboratory, Office of Research And DevelopmentU.S. Environmental Protection Agency, Research TriangleNorth CarolinaUSA

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