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An overview of transmissible spongiform encephalopathies

Published online by Cambridge University Press:  28 February 2007

K. Takemura ,
M. Kahdre ,
D. Joseph ,
A. Yousef  and
S. Sreevatsan
K. Takemura
Affiliation:
Food Animal Health Research Program, Department of Veterinary Preventive Medicine, Ohio Agricultural Research and Development Center, Ohio State University, Wooster, OH 44691, USA
M. Kahdre
Affiliation:
Department of Food Science and Technology, Ohio State University, Columbus, OH 43210, USA
D. Joseph
Affiliation:
Food Animal Health Research Program, Department of Veterinary Preventive Medicine, Ohio Agricultural Research and Development Center, Ohio State University, Wooster, OH 44691, USA
A. Yousef
Affiliation:
Department of Food Science and Technology, Ohio State University, Columbus, OH 43210, USA
S. Sreevatsan*
Affiliation:
Food Animal Health Research Program, Department of Veterinary Preventive Medicine, Ohio Agricultural Research and Development Center, Ohio State University, Wooster, OH 44691, USA
*
*E-mail: [email protected]
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Abstract

Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders of humans and animals associated with an accumulation of abnormal isoforms of prion protein (PrP) in nerve cells. The pathogenesis of TSEs involves conformational conversions of normal cellular PrP (PrPc) to abnormal isoforms of PrP (PrPSc). While the protein-only hypothesis has been widely accepted as a causal mechanism of prion diseases, evidence from more recent research suggests a possible involvement of other cellular component(s) or as yet undefined infectious agent(s) in PrP pathogenesis. Although the underlying mechanisms of PrP strain variation and the determinants of interspecies transmissibility have not been fully elucidated, biochemical and molecular findings indicate that bovine spongiform encephalopathy in cattle and new-variant Creutzfeldt–Jakob disease in humans are caused by indistinguishable etiological agent(s). Cumulative evidence suggests that there may be risks of humans acquiring TSEs via a variety of exposures to infected material. The development of highly precise ligands is warranted to detect and differentiate strains, allelic variants and infectious isoforms of these PrPs. This article describes the general features of TSEs and PrP, the current understanding of their pathogenesis, recent advances in prion disease diagnostics, and PrP inactivation.

Keywords

priontransmissible spongiform encephalopathiesbovine spongiform encephalopathyscrapieCreutzfeldt–Jakob diseasediagnostics
Type
Research Article
Information
Animal Health Research Reviews , Volume 5 , Issue 2 , December 2004 , pp. 103 - 124
Copyright
Copyright © CAB International 2004

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References

Adjou, KT, Demaimay, R, Deslys, JP, Lasmezas, CI, Beringue, V, Demart, S, Lamoury, F, Seman, M and Dormont, D (1999). MS-8209, a water-soluble amphotericin B derivative, affects both scrapie agent replication and PrPres accumulation in Syrian hamster scrapie. Journal of General Virology 80: 1079–1085.CrossRefGoogle ScholarPubMed
Aguzzi, A and Heikenwalder, M (2003). Prion diseases: cannibals and garbage piles. Nature 423: 127–129.Google Scholar
Anderson, RM, Donnelly, CA, Ferguson, NM, Woolhouse, ME, Watt, CJ, Udy, HJ, MaWhinney, S, Dunstan, SP, Southwood, TR, Wilesmith, JW, Ryan, JB, Hoinville, LJ, Hillerton, JE, Austin, AR and Wells, GA (1996). Transmission dynamics and epidemiology of BSE in British cattle. Nature 382: 779–788.Google Scholar
Archer, F, Bachelin, C, Andreoletti, O, Besnard, N, Perrot, G, Langevin, C, Le Dur, A, Vilette, D, Baron-Van Evercooren, A, Vilotte, JL and Laude, H (2004). Cultured peripheral neuroglial cells are highly permissive to sheep prion infection. Journal of Virology 78: 482–490.Google Scholar
Asante, EA, Linehan, JM, Desbruslais, M, Joiner, S, Gowland, I, Wood, AL, Welch, J, Hill, AF, Lloyd, SE, Wadsworth, JD and Collinge, J (2002). BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO Journal 21: 6358–6366.Google Scholar
Baron, T, Crozet, C, Biacabe, AG, Philippe, S, Verchere, J, Bencsik, A, Madec, JY, Calavas, D and Samarut, J (2004). Molecular analysis of the protease-resistant prion protein in scrapie and bovine spongiform encephalopathy transmitted to ovine transgenic and wild-type mice. Journal of Virology 78: 6243–6251.CrossRefGoogle ScholarPubMed
Basler, K, Oesch, B, Scott, M, Westaway, D, Walchli, M, Groth, DF, McKinley, MP, Prusiner, SB and Weissmann, C (1986). Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell 46: 417–428.Google Scholar
Beaudry, P, Cohen, P, Brandel, JP, Delasnerie-Laupretre, N, Richard, S, Launay, JM and Laplanche, JL (1999). 14–3-3 protein, neuron-specific enolase, and S-100 protein in cerebrospinal fluid of patients with Creutzfeldt–Jakob disease. Dementia and Geriatric Cognitive Disorders 10: 40–46.Google Scholar
Belt, PB, Muileman, IH, Schreuder, BE, Bos-de Ruijter, J, Gielkens, AL and Smits, MA (1995). Identification of five allelic variants of the sheep PrP gene and their association with natural scrapie. Journal of General Virology 76: 509–517.CrossRefGoogle ScholarPubMed
Birkett, CR, Hennion, RM, Bembridge, DA, Clarke, MC, Chree, A, Bruce, ME and Bostock, CJ (2001). Scrapie strains maintain biological phenotypes on propagation in a cell line in culture. EMBO Journal 20: 3351–3358.CrossRefGoogle Scholar
Bolton, DC, McKinley, MP and Prusiner, SB (1982). Identification of a protein that purifies with the scrapie prion. Science 218: 1309–1311.CrossRefGoogle ScholarPubMed
Bossers, A, Harders, FL and Smits, MA (1999). PrP genotype frequencies of the most dominant sheep breed in a country free from scrapie. Archives of Virology 144: 829–834.Google Scholar
Brandel, JP, Preece, M, Brown, P, Croes, E, Laplanche, JL, Agid, Y, Will, R and Alperovitch, A (2003). Distribution of codon 129 genotype in human growth hormone-treated CJD patients in France and the UK. Lancet 362: 128–130.Google Scholar
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 and Kretzschmar, H (1997). The cellular prion protein binds copper in vivo. Nature 390: 684–687.Google Scholar
Brown, P (2002). Drug therapy in human and experimental transmissible spongiform encephalopathy. Neurology 58: 1720–1725.CrossRefGoogle ScholarPubMed
Brown, P, Cathala, F, Raubertas, RF, Gajdusek, DC and Castaigne, P (1987). The epidemiology of Creutzfeldt–Jakob disease: conclusion of a 15-year investigation in France and review of the world literature. Neurology 37: 895–904.CrossRefGoogle ScholarPubMed
Brown, P, Liberski, PP, Wolff, A and Gajdusek, DC (1990). Resistance of scrapie infectivity to steam autoclaving after formaldehyde fixation and limited survival after ashing at 360 degrees C: practical and theoretical implications. Journal of Infectious Diseases 161: 467–472.Google Scholar
Brown, P, Gibbs, CJ Jr, Rodgers-Johnson, P, Asher, DM, Sulima, MP, Bacote, A, Goldfarb, LG and Gajdusek, DC (1994). Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Annals of Neurology 35: 513–529.CrossRefGoogle ScholarPubMed
Brown, P, Rau, EH, Johnson, BK, Bacote, AE, Gibbs, CJ Jr and Gajdusek, DC (2000). New studies on the heat resistance of hamster-adapted scrapie agent: threshold survival after ashing at 600 degrees C suggests an inorganic template of replication. Proceedings of the National Academy of Sciences of the United States of America 97: 3418–3421.Google Scholar
Bruce, ME, Will, RG, Ironside, JW, McConnell, I, Drummond, D, Suttie, A, McCardle, L, Chree, A, Hope, J, Birkett, C, Cousens, S, Fraser, H and Bostock, CJ (1997). Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389: 498–501.Google Scholar
Bruce, ME, Boyle, A, Cousens, S, McConnell, I, Foster, J, Goldmann, W and Fraser, H (2002). Strain characterization of natural sheep scrapie and comparison with BSE. Journal of General Virology 83: 695–704.CrossRefGoogle ScholarPubMed
Bueler, H, Fischer, M, Lang, Y, Bluethmann, H, Lipp, HP, DeArmond, SJ, Prusiner, SB, Aguet, M and Weissmann, C (1992). Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356: 577–582.CrossRefGoogle ScholarPubMed
Butler, DA, Scott, MR, Bockman, JM, Borchelt, DR, Taraboulos, A, Hsiao, KK, Kingsbury, DT and Prusiner, SB (1988). Scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins. Journal of Virology 62: 1558–1564.Google Scholar
Caspi, S, Halimi, M, Yanai, A, Sasson, SB, Taraboulos, A and Gabizon, R (1998). The anti-prion activity of Congo red. Putative mechanism. Journal of Biological Chemistry 273: 3484–3489.CrossRefGoogle ScholarPubMed
Caughey, B, Race, RE, Ernst, D, Buchmeier, MJ and Chesebro, B (1989). Prion protein biosynthesis in scrapie-infected and uninfected neuroblastoma cells. Journal of Virology 63: 175–181.CrossRefGoogle ScholarPubMed
Cervenakova, L, Brown, P, Soukharev, S, Yakovleva, O, Diringer, H, Saenko, EL and Drohan, WN (2003). Failure of immunocompetitive capillary electrophoresis assay to detect disease-specific prion protein in buffy coat from humans and chimpanzees with Creutzfeldt–Jakob disease. Electrophoresis 24: 853–859.Google Scholar
Chandler, RL (1961). Encephalopathy in mice produced by inoculation with scrapie brain material. Lancet 277: 1378–1379.Google Scholar
Chernoff, YO (2001). Mutation processes at the protein level: is Lamarck back? Mutation Research 488: 39–64.Google Scholar
Chernoff, YO, Lindquist, SL, Ono, B, Inge-Vechtomov, SG and Liebman, SW (1995). Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]. Science 268: 880–884.Google Scholar
Chiesa, R, Piccardo, P, Ghetti, B and Harris, DA (1998). Neurological illness in transgenic mice expressing a prion protein with an insertional mutation. Neuron 21: 1339–1351.Google Scholar
Chiesa, R, Piccardo, P, Quaglio, E, Drisaldi, B, Si-Hoe, SL, Takao, M, Ghetti, B and Harris, DA (2003). Molecular distinction between pathogenic and infectious properties of the prion protein. Journal of Virology 77: 7611–7622.CrossRefGoogle ScholarPubMed
Clarke, MC and Haig, DA (1970). Evidence for the multiplication of scrapie agent in cell culture. Nature 225: 100–101.Google Scholar
Collinge, J, Palmer, MS and Dryden, AJ (1991). Genetic predisposition to iatrogenic Creutzfeldt–Jakob disease. Lancet 337: 1441–1442.Google Scholar
Collinge, J, Beck, J, Campbell, T, Estibeiro, K and Will, RG (1996a). Prion protein gene analysis in new variant cases of Creutzfeldt–Jakob disease. Lancet. 348: 56.Google Scholar
Collinge, J, Sidle, KC, Meads, J, Ironside, J and Hill, AF (1996b). Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383: 685–690.Google Scholar
Cordeiro, Y, Machado, F, Juliano, L, Juliano, MA, Brentani, RR, Foguel, D and Silva, JL (2001). DNA converts cellular prion protein into the beta-sheet conformation and inhibits prion peptide aggregation. Journal of Biological Chemistry 276: 49400–49409.CrossRefGoogle ScholarPubMed
Dealler, S and Rainov, NG (2003). Pentosan polysulfate as a prophylactic and therapeutic agent against prion disease. IDrugs 6: 470–478.Google ScholarPubMed
Deleault, NR, Lucassen, RW and Supattapone, S (2003). RNA molecules stimulate prion protein conversion. Nature 425: 717–720.CrossRefGoogle ScholarPubMed
Demaimay, R, Harper, J, Gordon, H, Weaver, D, Chesebro, B and Caughey, B (1998). Structural aspects of Congo red as an inhibitor of protease-resistant prion protein formation. Journal of Neurochemistry 71: 2534–2541.CrossRefGoogle ScholarPubMed
Derkatch, IL, Chernoff, YO, Kushnirov, VV, Inge-Vechtomov, SG and Liebman, SW (1996). Genesis and variability of [PSI] prion factors in Saccharomyces cerevisiae. Genetics 144: 1375–1386.Google Scholar
Dickinson, AG (1976). Scrapie in sheep and goats. In: Kimberlin, RH, editors. Slow Virus Diseases of Animals and Man. Amsterdam: North-Holland.Google Scholar
Doh-ura, K, Ishikawa, K, Murakami-Kubo, I, Sasaki, K, Mohri, S, Race, R and Iwaki, T (2004). Treatment of transmissible spongiform encephalopathy by intraventricular drug infusion in animal models. Journal of Virology 78: 4999–5006.CrossRefGoogle ScholarPubMed
Donne, DG, Viles, JH, Groth, D, Mehlhorn, I, James, TL, Cohen, FE, Prusiner, SB, Wright, PE and Dyson, HJ (1997). Structure of the recombinant full-length hamster prion protein PrP(29–231): the N terminus is highly flexible. Proceedings of the National Academy of Sciences of the United States of America 94: 13452–13457.Google Scholar
Donnelly, CA, Ferguson, NM, Ghani, AC and Anderson, RM (2002). Implications of BSE infection screening data for the scale of the British BSE epidemic and current European infection levels. Proceedings of the Royal Society of London Series B Biological Sciences 269: 2179–2190.Google Scholar
Drisaldi, B, Stewart, RS, Adles, C, Stewart, LR, Quaglio, E, Biasini, E, Fioriti, L, Chiesa, R and Harris, DA (2003). Mutant PrP is delayed in its exit from the endoplasmic reticulum, but neither wild-type nor mutant PrP undergoes retrotranslocation prior to proteasomal degradation. Journal of Biological Chemistry 278: 21732–21743.CrossRefGoogle ScholarPubMed
Dyer, O (2003). Family finds hospital willing to give experimental CJD treatment. BMJ 326: 8.Google Scholar
Ferguson, NM, Ghani, AC, Donnelly, CA, Hagenaars, TJ and Anderson, RM (2002). Estimating the human health risk from possible BSE infection of the British sheep flock. Nature 415: 420–424.CrossRefGoogle ScholarPubMed
Forloni, G, Iussich, S, Awan, T, Colombo, L, Angeretti, N, Girola, L, Bertani, I, Poli, G, Caramelli, M, Grazia, BM, Farina, L, Limido, L, Rossi, G, Giaccone, G, Ironside, JW, Bugiani, O, Salmona, M and Tagliavini, F (2002). Tetracyclines affect prion infectivity. Proceedings of the National Academy of Sciences of the United States of America 99: 10849–10854.Google Scholar
Foster, JD, Hope, J and Fraser, H (1993). Transmission of bovine spongiform encephalopathy to sheep and goats. Veterinary Record 133: 339–341.Google Scholar
Gajdusek, DC and Zigas, V (1957). Degenerative disease of the central nervous system in New Guinea: the endemic occurrence of kuru in the native population. New England Journal of Medicine 257: 974–978.Google Scholar
Goldfarb, LG, Petersen, RB, Tabaton, M, Brown, P, LeBlanc, AC, Montagna, P, Cortelli, P, Julien, J, Vital, C and Pendelbury, WW (1992). Fatal familial insomnia and familial Creutzfeldt–Jakob disease: disease phenotype determined by a DNA polymorphism. Science 258: 806–808.CrossRefGoogle ScholarPubMed
Goldgaber, D, Goldfarb, LG, Brown, P, Asher, DM, Brown, WT, Lin, S, Teener, JW, Feinstone, SM, Rubenstein, R and Kascsak, RJ (1989). Mutations in familial Creutzfeldt–Jakob disease and Gerstmann–Straussler–Scheinker's syndrome. Experimental Neurology 106: 204–206.Google Scholar
Goldmann, W, Hunter, N, Benson, G, Foster, JD and Hope, J (1991). Different scrapie-associated fibril proteins (PrP) are encoded by lines of sheep selected for different alleles of the Sip gene. Journal of General Virology 72: 2411–2417.Google Scholar
Goldmann, W, Hunter, N, Smith, G, Foster, J and Hope, J (1994). PrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie. Journal of General Virology 75: 989–995.Google Scholar
Gould, M (2003). Medicines committee felt unable to recommend use of pentosan polyphosphate in vCJD. BMJ 327: 770.Google Scholar
Graner, E, Mercadante, AF, Zanata, SM, Forlenza, OV, Cabral, AL, Veiga, SS, Juliano, MA, Roesler, R, Walz, R, Minetti, A, Izquierdo, I, Martins, VR and Brentani, RR (2000). Cellular prion protein binds laminin and mediates neuritogenesis. Brain Research Molecular Brain Research 76: 85–92.Google Scholar
Hadlow, WJ, Kennedy, RC and Race, RE (1982). Natural infection of Suffolk sheep with scrapie virus. Journal of Infectious Diseases 146: 657–664.Google Scholar
Hainfellner, JA, Brantner-Inthaler, S, Cervenakova, L, Brown, P, Kitamoto, T, Tateishi, J, Diringer, H, Liberski, PP, Regele, H and Feucht, M (1995). The original Gerstmann– Straussler–Scheinker family of Austria: divergent clinicopathological phenotypes but constant PrP genotype. Brain Pathology 5: 201–211.CrossRefGoogle ScholarPubMed
Hegde, RS, Mastrianni, JA, Scott, MR, DeFea, KA, Tremblay, P, Torchia, M, DeArmond, SJ, Prusiner, SB and Lingappa, VR (1998). A transmembrane form of the prion protein in neurodegenerative disease. Science 279: 827–834.Google Scholar
Heldt, N, Boellaard, JW, Brown, P, Cervenakova, L, Doerr-Schott, J, Thomas, C, Scherer, C and Rohmer, F (1998). Gerstmann–Straussler–Scheinker disease with A117V mutation in a second French-Alsatian family. Clinical Neuropathology 17: 229–234.Google Scholar
Hill, AF, Antoniou, M and Collinge, J (1999a). Protease-resistant prion protein produced in vitro lacks detectable infectivity. Journal of General Virology 80: 11–14.Google Scholar
Hill, AF, Butterworth, RJ, Joiner, S, Jackson, G, Rossor, MN, Thomas, DJ, Frosh, A, Tolley, N, Bell, JE, Spencer, M, King, A, Al Sarraj, S, Ironside, JW, Lantos, PL and Collinge, J (1999b). Investigation of variant Creutzfeldt–Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 353: 183–189.Google Scholar
Hope, J, Wood, SC, Birkett, CR, Chong, A, Bruce, ME, Cairns, D, Goldmann, W, Hunter, N and Bostock, CJ (1999). Molecular analysis of ovine prion protein identifies similarities between BSE and an experimental isolate of natural scrapie, CH1641. Journal of General Virology 80: 1–4.Google Scholar
Hornshaw, MP, McDermott, JR and Candy, JM (1995). Copper binding to the N-terminal tandem repeat regions of mammalian and avian prion protein. Biochemical and Biophysical Research Communications 207: 621–629.Google Scholar
Hourrigan, (1979). Epidemiology of scrapie in the United States. In: Prusiner, S and Hadlow, WJ, editors. Slow Transmissible Diseases of the Nervous System. New York: Academic Press, pp. 331–356.Google Scholar
Houston, EF, Halliday, SI, Jeffrey, M, Goldmann, W and Hunter, N (2002). New Zealand sheep with scrapie-susceptible PrP genotypes succumb to experimental challenge with a sheep-passaged scrapie isolate (SSBP/1). Journal of General Virology 83: 1247–1250.Google Scholar
Hsich, G, Kenney, K and Gibbs, CJ, Lee, KH and Harrington, MG (1996). The 14–3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. New England Journal of Medicine 335: 924–930.Google Scholar
Hunter, N and Cairns, D (1998). Scrapie-free Merino and Poll Dorset sheep from Australia and New Zealand have normal frequencies of scrapie-susceptible PrP genotypes. Journal of General Virology 79: 2079–2082.Google Scholar
Hunter, N, Goldmann, W, Benson, G, Foster, JD and Hope, J (1993). Swaledale sheep affected by natural scrapie differ significantly in PrP genotype frequencies from healthy sheep and those selected for reduced incidence of scrapie. Journal of General Virology 74: 1025–1031.Google Scholar
Hunter, N, Foster, JD, Goldmann, W, Stear, MJ, Hope, J and Bostock, C (1996). Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes. Archives of Virology 141: 809–824.CrossRefGoogle Scholar
Hunter, N, Cairns, D, Foster, JD, Smith, G, Goldmann, W and Donnelly, K (1997a). Is scrapie solely a genetic disease? Nature 386: 137.Google Scholar
Hunter, N, Moore, L, Hosie, BD, Dingwall, WS and Greig, A (1997b). Association between natural scrapie and PrP genotype in a flock of Suffolk sheep in Scotland. Veterinary Record 140: 59–63.Google Scholar
Ikeda, T, Horiuchi, M, Ishiguro, N, Muramatsu, Y, Kai-Uwe, GD and Shinagawa, M (1995). Amino acid polymorphisms of PrP with reference to onset of scrapie in Suffolk and Corriedale sheep in Japan. Journal of General Virology 76: 2577–2581.Google Scholar
Ironside, JW (1998). Neuropathological findings in new variant CJD and experimental transmission of BSE. FEMS Immunology and Medical Microbiology 21: 91–95.Google Scholar
Joly, DO, Ribic, CA, Langenberg, JA, Beheler, K, Batha, CA, Dhuey, BJ, Rolley, RE, Bartelt, G, Van Deelen, TR and Samuel, MD (2003). Chronic wasting disease in free-ranging Wisconsin White-tailed Deer. Emerging Infectious Diseases 9: 599–601.Google Scholar
Kaneko, K, Ball, HL, Wille, H, Zhang, H, Groth, D, Torchia, M, Tremblay, P, Safar, J, Prusiner, SB, DeArmond, SJ, Baldwin, MA and Cohen, FE (2000). A synthetic peptide initiates Gerstmann–Straussler–Scheinker (GSS) disease in transgenic mice. Journal of Molecular Biology 295: 997–1007.Google Scholar
Kao, RR, Gravenor, MB, Baylis, M, Bostock, CJ, Chihota, CM, Evans, JC, Goldmann, W, Smith, AJ and McLean, AR (2002). The potential size and duration of an epidemic of bovine spongiform encephalopathy in British sheep. Science 295: 332–335.CrossRefGoogle ScholarPubMed
Kenney, K, Brechtel, C, Takahashi, H, Kurohara, K, Anderson, P, Gibbs, CJ Jr (2000). An enzyme-linked immunosorbent assay to quantify 14–3-3 proteins in the cerebrospinal fluid of suspected Creutzfeldt–Jakob disease patients. Annals of Neurology 48: 395–398.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
Kocisko, DA, Come, JH, Priola, SA, Chesebro, B, Raymond, GJ, Lansbury, PT and Caughey, B (1994). Cell-free formation of protease-resistant prion protein. Nature 370: 471–474.Google Scholar
Korth, C, Stierli, B, Streit, P, Moser, M, Schaller, O, Fischer, R, Schulz-Schaeffer, W, Kretzschmar, H, Raeber, A, Braun, U, Ehrensperger, F, Hornemann, S, Glockshuber, R, Riek, R, Billeter, M, Wuthrich, K and Oesch, B (1997). Prion (PrPSc)-specific epitope defined by a monoclonal antibody. Nature 390: 74–77.Google Scholar
Korth, C, May, BC, Cohen, FE and Prusiner, SB (2001). Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proceedings of the National Academy of Sciences of the United States of America 98: 9836–9841.CrossRefGoogle ScholarPubMed
Koster, T, Singh, K, Zimmermann, M and Gruys, E (2003). Emerging therapeutic agents for transmissible spongiform encephalopathies: a review. Journal of Veterinary Pharmacology and Therapeutics 26: 315–326.Google Scholar
Kretzschmar, HA, Stowring, LE, Westaway, D, Stubblebine, WH, Prusiner, SB and DeArmond, SJ (1986). Molecular cloning of a human prion protein cDNA. DNA 5: 315–324.Google Scholar
Kretzschmar, HA, Tings, T, Madlung, A, Giese, A and Herms, J (2000). Function of PrP(C) as a copper-binding protein at the synapse. Archives of Virology Supplementum 16: 239–249.Google Scholar
Lasmezas, CI, Deslys, JP, Demaimay, R, Adjou, KT, Lamoury, F, Dormont, D, Robain, O, Ironside, J and Hauw, JJ (1996). BSE transmission to macaques. Nature 381: 743–744.Google Scholar
Lee, HS, Sambuughin, N, Cervenakova, L, Chapman, J, Pocchiari, M, Litvak, S, Qi, HY, Budka, H, del Ser, T, Furukawa, H, Brown, P, Gajdusek, DC, Long, JC, Korczyn, AD and Goldfarb, LG (1999). Ancestral origins and worldwide distribution of the PRNP 200K mutation causing familial Creutzfeldt–Jakob disease. American Journal of Human Genetics 64: 1063–1070.Google Scholar
Legname, G, Baskakov, IV, Nguyen, HB, Riesner, D, Cohen, FE, DeArmond, SJ and Prusiner, PB (2004). Synthetic mammalian prions. Science 305: 673–676.Google Scholar
Liberski, PP, Barcikowska, M, Cervenakova, L, Bratosiewicz, J, Marczewska, M, Brown, P and Gajdusek, DC (1998). A case of sporadic Creutzfeldt–Jakob disease with a Gerstmann– Straussler–Scheinker phenotype but no alterations in the PRNP gene. Acta Neuropathologica 96: 425–430.Google Scholar
Ma, J and Lindquist, S (2002). Conversion of PrP to a self- perpetuating PrPSc-like conformation in the cytosol. Science 298: 1785–1788.Google Scholar
Ma, J, Wollmann, R and Lindquist, S (2002). Neurotoxicity and neurodegeneration when PrP accumulates in the cytosol. Science 298: 1781–1785.Google Scholar
Manson, JC, Clarke, AR, Hooper, ML, Aitchison, L, McConnell, I and Hope, J (1994). 129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal. Molecular Neurobiology 8: 121–127.Google Scholar
Manson, JC, Barron, R, Jamieson, E, Baybutt, H, Tuzi, N, McConnell, I, Melton, D, Hope, J and Bostock, C (2000). A single amino acid alteration in murine PrP dramatically alters TSE incubation time. Archives of Virology Supplementum 16: 95–102.Google Scholar
Marsh, RF and Hadlow, WJ (1992). Transmissible mink encephalopathy. Revue Scientifique et Technique (International Office of Epizootics) 11: 539–550.Google Scholar
Marsh, RF and Kimberlin, RH (1975). Comparison of scrapie and transmissible mink encephalopathy in hamsters. II. Clinical signs, pathology, and pathogenesis. Journal of Infectious Diseases 131: 104–110.CrossRefGoogle Scholar
May, BC, Fafarman, AT, Hong, SB, Rogers, M, Deady, LW, Prusiner, SB and Cohen, FE (2003). Potent inhibition of scrapie prion replication in cultured cells by bis-acridines. Proceedings of the National Academy of Sciences of the United States of America 100: 3416–3421.Google Scholar
Mead, S, Mahal, SP, Beck, J, Campbell, T, Farrall, M, Fisher, E and Collinge, J (2001). Sporadic—but not variant—Creutzfeldt–Jakob disease is associated with polymorphisms upstream of PRNP exon 1. American Journal of Human Genetics 69: 1225–1235.CrossRefGoogle Scholar
Mead, S, Stumpf, MP, Whitfield, J, Beck, JA, Poulter, M, Campbell, T, Uphill, JB, Goldstein, D, Alpers, M, Fisher, EM and Collinge, J (2003). Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics. Science 300: 640–643.Google Scholar
Medori, R, Tritschler, HJ, LeBlanc, A, Villare, F, Manetto, V, Chen, HY, Xue, R, Leal, S, Montagna, P and Cortelli, P (1992). Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene. New England Journal of Medicine 326: 444–449.Google Scholar
Meggio, F, Negro, A, Sarno, S, Ruzzene, M, Bertoli, A, Sorgato, MC and Pinna, LA (2000). Bovine prion protein as a modulator of protein kinase CK2. Biochemical Journal 352: 191–196.Google Scholar
Mellon, PL, Windle, JJ, Goldsmith, PC, Padula, CA, Roberts, JL and Weiner, RI (1990). Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis. Neuron 5: 1–10.Google Scholar
Miele, G, Manson, J and Clinton, M (2001). A novel erythroid-specific marker of transmissible spongiform encephalopathies. Nature Medicine 7: 361–364.Google Scholar
Miller, MW, Wild, MA and Williams, ES (1998). Epidemiology of chronic wasting disease in captive Rocky Mountain elk. Journal of Wildlife Diseases 34: 532–538.Google Scholar
Miller, MW, Williams, ES, McCarty, CW, Spraker, TR, Kreeger, TJ, Larsen, CT and Thorne, ET (2000). Epizootiology of chronic wasting disease in free-ranging cervids in Colorado and Wyoming. Journal of Wildlife Diseases 36: 676–690.Google Scholar
Mouillet-Richard, S, Ermonval, M, Chebassier, C, Laplanche, JL, Lehmann, S, Launay, JM and Kellermann, O (2000). Signal transduction through prion protein. Science 289: 1925–1928.Google Scholar
Muramoto, T, DeArmond, SJ, Scott, M, Telling, GC, Cohen, FE and Prusiner, SB (1997). Heritable disorder resembling neuronal storage disease in mice expressing prion protein with deletion of an alpha-helix. Nature Medicine 3: 750–755.Google Scholar
Murphy, C, Breen, C, Rogers, M and Giese, M (2001). Interferon gamma and prostaglandin in BSE-infected cattle. Cytokine 13: 169–173.Google Scholar
Nakajima, M, Yamada, T, Kusuhara, T, Furukawa, H, Takahashi, M, Yamauchi, A and Kataoka, Y (2004). Results of quinacrine administration to patients with Creutzfeldt–Jakob disease. Dementia and Geriatric Cognitive Disorders 17: 158–163.Google Scholar
Nandi, PK and Leclerc, E (1999). Polymerization of murine recombinant prion protein in nucleic acid solution. Archives of Virology 144: 1751–1763.Google Scholar
Naslavsky, N, Stein, R, Yanai, A, Friedlander, G and Taraboulos, A (1997). Characterization of detergent-insoluble complexes containing the cellular prion protein and its scrapie isoform. Journal of Biological Chemistry 272: 6324–6331.Google Scholar
O'Rourke, KI, Besser, TE, Miller, MW, Cline, TF, Spraker, TR, Jenny, AL, Wild, MA, Zebarth, GL and Williams, ES (1999). PrP genotypes of captive and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease. Journal of General Virology 80: 2765–2769.CrossRefGoogle ScholarPubMed
O'Rourke, KI, Baszler, TV, Besser, TE, Miller, JM, Cutlip, RC, Wells, GA, Ryder, SJ, Parish, SM, Hamir, AN, Cockett, NE, Jenny, A and Knowles, DP (2000). Preclinical diagnosis of scrapie by immunohistochemistry of third eyelid lymphoid tissue. Journal of Clinical Microbiology 38: 3254–3259.Google Scholar
Otto, M, Wiltfang, J, Tumani, H, Zerr, I, Lantsch, M, Kornhuber, J, Weber, T, Kretzschmar, HA and Poser, S (1997). Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt–Jakob disease. Neuroscience Letters 225: 210–212.Google Scholar
Otto, M, Beekes, M, Wiltfang, J, Bahn, E, Poser, S and Diringer, H (1998a). Elevated levels of serum S100 beta protein in scrapie hamsters. Journal of Neurovirology 4: 572–573.Google Scholar
Otto, M, Wiltfang, J, Schutz, E, Zerr, I, Otto, A, Pfahlberg, A, Gefeller, O, Uhr, M, Giese, A, Weber, T, Kretzschmar, HA and Poser, S (1998b). Diagnosis of Creutzfeldt–Jakob disease by measurement of S100 protein in serum: prospective case-control study. BMJ (Clinical Research Ed.) 316: 577–582.CrossRefGoogle ScholarPubMed
Otto, M, Bahn, E, Wiltfang, J, Boekhoff, I and Beuche, W (1998c). Decrease of S100 beta protein in serum of patients with amyotrophic lateral sclerosis. Neuroscience Letters 240: 171–173.CrossRefGoogle ScholarPubMed
Otto, M, Wiltfang, J, Cepek, L, Neumann, M, Mollenhauer, B, Steinacker, P, Ciesielczyk, B, Schulz-Schaeffer, W, Kretzschmar, HA and Poser, S (2002). Tau protein and 14–3-3 protein in the differential diagnosis of Creutzfeldt–Jakob disease. Neurology 58: 192–197.Google Scholar
Palmer, MS, Dryden, AJ, Hughes, JT and Collinge, J (1991). Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob disease. Nature 352: 340–342.Google Scholar
Pan, KM, Baldwin, M, Nguyen, J, Gasset, M, Serban, A, Groth, D, Mehlhorn, I, Huang, Z, Fletterick, RJ and Cohen, FE (1993). Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Proceedings of the National Academy of Sciences of the United States of America 90: 10962–10966.Google Scholar
Paramithiotis, E, Pinard, M, Lawton, T, LaBoissiere, S, Leathers, VL, Zou, WQ, Estey, LA, Lamontagne, J, Lehto, MT, Kondejewski, LH, Francoeur, GP, Papadopoulos, M, Haghighat, A, Spatz, SJ, Head, M, Will, R, Ironside, J, O'Rourke, K, Tonelli, Q, Ledebur, HC, Chakrabartty, A and Cashman, NR (2003). A prion protein epitope selective for the pathologically misfolded conformation. Nature Medicine 9: 893–899.Google Scholar
Parchi, P, Castellani, R, Capellari, S, Ghetti, B, Young, K, Chen, SG, Farlow, M, Dickson, DW, Sima, AA, Trojanowski, JQ, Petersen, RB and Gambetti, P (1996). Molecular basis of phenotypic variability in sporadic Creutzfeldt–Jakob disease. Annals of Neurology 39: 767–778.CrossRefGoogle ScholarPubMed
Parry, HB (1983). Scrapie Disease in Sheep: Historical, Clinical, Epidemiological, Pathological, and Practical Aspects of the Natural Disease. London: Academic Press.Google Scholar
Parsell, DA, Kowal, AS, Singer, MA and Lindquist, S (1994). Protein disaggregation mediated by heat-shock protein Hsp104. Nature 372: 475–478.Google Scholar
Pattison, IH, Hoare, MN, Jebbett, JN and Watson, WA (1972). Spread of scrapie to sheep and goats by oral dosing with foetal membranes from scrapie-affected sheep. Veterinary Record 90: 465–468.Google Scholar
Prusiner, SB (1982). Novel proteinaceous infectious particles cause scrapie. Science 216: 136–144.Google Scholar
Prusiner, SB (1998). Prions. Proceedings of the National Academy of Sciences of the United States of America 95: 13363–13383.Google Scholar
Prusiner, SB, Groth, DF, Bolton, DC, Kent, SB and Hood, LE (1984). Purification and structural studies of a major scrapie prion protein. Cell 38: 127–134.Google Scholar
Race, RE, Fadness, LH and Chesebro, B (1987). Characterization of scrapie infection in mouse neuroblastoma cells. Journal of General Virology 68: 1391–1399.CrossRefGoogle ScholarPubMed
Raymond, GJ, Bossers, A, Raymond, LD, O'Rourke, KI, McHolland, LE, Bryant, PK III, Miller, MW, Williams, ES, Smits, M and Caughey, B (2000). Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease. EMBO Journal 19: 4425–4430.Google Scholar
Rieger, R, Edenhofer, F, Lasmezas, CI and Weiss, S (1997). The human 37-kDa laminin receptor precursor interacts with the prion protein in eukaryotic cells. Nature Medicine 3: 1383–1388.Google Scholar
Riek, R, Hornemann, S, Wider, G, Glockshuber, R and Wuthrich, K (1997). NMR characterization of the full-length recombinant murine prion protein, mPrP(23–231). FEBS Letters 413: 282–288.Google Scholar
Riek, R, Wider, G, Billeter, M, Hornemann, S, Glockshuber, R and Wuthrich, K (1998). Prion protein NMR structure and familial human spongiform encephalopathies. Proceedings of the National Academy of Sciences of the United States of America 95: 11667–11672.Google Scholar
Rubenstein, R, Carp, RI and Callahan, SM (1984). In vitro replication of scrapie agent in a neuronal model: infection of PC12 cells. Journal of General Virology 65: 2191–2198.Google Scholar
Saborio, GP, Soto, C, Kascsak, RJ, Levy, E, Kascsak, R, Harris, DA and Frangione, B (1999). Cell-lysate conversion of prion protein into its protease-resistant isoform suggests the participation of a cellular chaperone. Biochemical and Biophysical Research Communications 258: 470–475.Google Scholar
Saborio, GP, Permanne, B and Soto, C (2001). Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411: 810–813.Google Scholar
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 and Williamson, RA (2002). Measuring prions causing bovine spongiform encephalopathy or chronic wasting disease by immunoassays and transgenic mice. Nature Biotechnology 20: 1147–1150.Google Scholar
Schatzl, HM, Laszlo, L, Holtzman, DM, Tatzelt, J, DeArmond, SJ, Weiner, RI, Mobley, WC and Prusiner, SB (1997). A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis. Journal of Virology 71: 8821–8831.Google Scholar
Schmerr, MJ, Jenny, AL, Bulgin, MS, Miller, JM, Hamir, AN, Cutlip, RC and Goodwin, KR (1999). Use of capillary electrophoresis and fluorescent labeled peptides to detect the abnormal prion protein in the blood of animals that are infected with a transmissible spongiform encephalopathy. Journal of Chromatography A 853: 207–214.Google Scholar
Shorter, J and Lindquist, S (2004). Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformers. Science 304: 1793–1797.Google Scholar
Sigurdson, CJ and Miller, MW (2003). Other animal prion diseases. British Medical Bulletin 66: 199–212.Google Scholar
Sigurdson, CJ, Williams, ES, Miller, MW, Spraker, TR, O'Rourke, KI and Hoover, EA (1999). Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus). Journal of General Virology 80: 2757–2764.Google Scholar
Sohn, HJ, Kin, JH, Choi, KS, Nah, JJ, Joo, YS, Jean, YH, Ahn, SW, Kim, OK, Kin, DY and Balachandran, A (2002). A case of chronic wasting disease in an elk imported to Korea from Canada. Journal of Veterinary Medical Science 64: 855–858.Google Scholar
Solassol, J, Crozet, C and Lehmann, S (2003). Prion propagation in cultured cells. British Medical Bulletin 66: 87–97.Google Scholar
Solforosi, L, Criado, JR, McGavern, DB, Wirz, S, Sanchez-Alavez, M, Sugama, S, DeGiorgio, LA, Volpe, BT, Wiseman, E, Abalos, G, Masliah, E, Gilden, D, Oldstone, MB, Conti, B and Williamson, RA (2004). Cross-linking cellular prion protein triggers neuronal apoptosis in vivo. Science 303: 1514–1516.Google Scholar
Soto, C, Saborio, GP and Anderes, L (2002). Cyclic amplification of protein misfolding: application to prion-related disorders and beyond. Trends in Neurosciences 25: 390–394.Google Scholar
Spielhaupter, C and Schatzl, HM (2001). PrPC directly interacts with proteins involved in signaling pathways. Journal of Biological Chemistry 276: 44604–44612.Google Scholar
Spraker, TR, Miller, MW, Williams, ES, Getzy, DM, Adrian, WJ, Schoonveld, GG, Spowart, RA, O'Rourke, KI, Miller, JM and Merz, PA (1997). Spongiform encephalopathy in free-ranging mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus) and Rocky Mountain elk (Cervus elaphus nelsoni) in northcentral Colorado. Journal of Wildlife Diseases 33: 1–6.Google Scholar
Spraker, TR, Zink, RR, Cummings, BA, Wild, MA, Miller, MW and O'Rourke, KI (2002). Comparison of histological lesions and immunohistochemical staining of proteinase-resistant prion protein in a naturally occurring spongiform encephalopathy of free-ranging mule deer (Odocoileus hemionus) with those of chronic wasting disease of captive mule deer. Veterinary Pathology 39: 110–119.Google Scholar
Stack, MJ, Chaplin, MJ and Clark, J (2002). Differentiation of prion protein glycoforms from naturally occurring sheep scrapie, sheep-passaged scrapie strains (CH1641 and SSBP1), bovine spongiform encephalopathy (BSE) cases and Romney and Cheviot breed sheep experimentally inoculated with BSE using two monoclonal antibodies. Acta Neuropathologica 104: 279–286.Google Scholar
Stahl, N, Borchelt, DR, Hsiao, K and Prusiner, SB (1987). Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell 51: 229–240.Google Scholar
Stahl, N, Baldwin, MA, Hecker, R, Pan, KM, Burlingame, AL and Prusiner, SB (1992). Glycosylinositol phospholipid anchors of the scrapie and cellular prion proteins contain sialic acid. Biochemistry 31: 5043–5053.Google Scholar
Stetter, KO (1996). Hyperthermophiles in the history of life. Ciba Foundation Symposium 202: 1–10.Google Scholar
Stetter, KO (1999). Extremophiles and their adaptation to hot environments. FEBS Letters 452: 22–25.Google Scholar
Swietnicki, W, Petersen, RB, Gambetti, P and Surewicz, WK (1998). Familial mutations and the thermodynamic stability of the recombinant human prion protein. Journal of Biological Chemistry 273: 31048–31052.Google Scholar
Tagliavini, F, McArthur, RA, Canciani, B, Giaccone, G, Porro, M, Bugiani, M, Lievens, PM, Bugiani, O, Peri, E, Dall'Ara, P, Rocchi, M, Poli, G, Forloni, G, Bandiera, T, Varasi, M, Suarato, A, Cassutti, P, Cervini, MA, Lansen, J, Salmona, M and Post, C (1997). Effectiveness of anthracycline against experimental prion disease in Syrian hamsters. Science 276: 1119–1122.Google Scholar
Taylor, D (1996). Inactivation of the causal agents of Creutzfeldt–Jakob disease and other human prion diseases. Brain Pathology 6: 197–198.Google Scholar
Taylor, DM (1999). Inactivation of prions by physical and chemical means. Journal of Hospital Infection 43: S69–S76.Google Scholar
Taylor, DM (2000). Inactivation of transmissible degenerative encephalopathy agents: A review. Veterinary Journal 159: 10–17.Google Scholar
Taylor, DM and Fernie, K (1996). Exposure to autoclaving or sodium hydroxide extends the dose–response curve of the 263K strain of scrapie agent in hamsters. Journal of General Virology 77: 811–813.Google Scholar
Taylor, DM and McConnell, I (1988). Autoclaving does not decontaminate formol-fixed scrapie tissues. Lancet 1: 1463–1464.Google Scholar
Taylor, DM and Woodgate, SL (2003). Rendering practices and inactivation of transmissible spongiform encephalopathy agents. Revue Scientifique et Technique (International Office of Epizootics) 22: 297–310.Google Scholar
Telling, GC (2000). Prion protein genes and prion diseases: studies in transgenic mice. Neuropathology and Applied Neurobiology 26: 209–220.Google Scholar
Telling, GC, Scott, M, Hsiao, KK, Foster, D, Yang, SL, Torchia, M, Sidle, KC, Collinge, J, DeArmond, SJ and Prusiner, SB (1994). Transmission of Creutzfeldt–Jakob disease from humans to transgenic mice expressing chimeric human–mouse prion protein. Proceedings of the National Academy of Sciences of the United States of America 91: 9936–9940.CrossRefGoogle ScholarPubMed
Telling, GC, Scott, M, Mastrianni, J, Gabizon, R, Torchia, M, Cohen, FE, DeArmond, SJ and Prusiner, SB (1995). Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell 83: 79–90.Google Scholar
Thuring, CM, Erkens, JH, Jacobs, JG, Bossers, A, Van Keulen, LJ, Garssen, GJ, Van Zijderveld, FG, Ryder, SJ, Groschup, MH, Sweeney, T and Langeveld, JP (2004). Discrimination between scrapie and bovine spongiform encephalopathy in sheep by molecular size, immunoreactivity, and glycoprofile of prion protein. Journal of Clinical Microbiology 42: 972–980.Google Scholar
Tremblay, P, Ball, HL, Kaneko, K, Groth, D, Hegde, RS, Cohen, FE, DeArmond, SJ, Prusiner, SB and Safar, JG (2004). Mutant PrPSc conformers induced by a synthetic peptide and several prion strains. Journal of Virology 78: 2088–2099.Google Scholar
Tsai, B, Ye, Y and Rapoport, TA (2002). Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nature Reviews Molecular Cell Biology 3: 246–255.Google Scholar
Turk, E, Teplow, DB, Hood, LE and Prusiner, SB (1988). Purification and properties of the cellular and scrapie hamster prion proteins. European Journal Of Biochemistry 176: 21–30.Google Scholar
Vey, M, Pilkuhn, S, Wille, H, Nixon, R, DeArmond, SJ, Smart, EJ, Anderson, RG, Taraboulos, A and Prusiner, SB (1996). Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains. Proceedings of the National Academy of Sciences of the United States of America 93: 14945–14949.Google Scholar
Vilette, D, Andreoletti, O, Archer, F, Madelaine, MF, Vilotte, JL, Lehmann, S and Laude, H (2001). Ex vivo propagation of infectious sheep scrapie agent in heterologous epithelial cells expressing ovine prion protein. Proceedings of the National Academy of Sciences of the United States of America 98: 4055–4059.Google Scholar
Wadsworth, JD, Joiner, S, Hill, AF, Campbell, TA, Desbruslais, M, Luthert, PJ and Collinge, J (2001). Tissue distribution of protease resistant prion protein in variant Creutzfeldt–Jakob disease using a highly sensitive immunoblotting assay. Lancet 358: 171–180.Google Scholar
Wadsworth, JD, Hill, AF, Beck, JA and Collinge, J (2003). Molecular and clinical classification of human prion disease. British Medical Bulletin 66: 241–254.Google Scholar
Weiss, S, Proske, D, Neumann, M, Groschup, MH, Kretzschmar, HA, Famulok, M and Winnacker, EL (1997). RNA aptamers specifically interact with the prion protein PrP. Journal of Virology 71: 8790–8797.Google Scholar
Weissmann, C and Flechsig, E (2003). PrP knock-out and PrP transgenic mice in prion research. British Medical Bulletin 66: 43–60.Google Scholar
Weissmann, C, Enari, M, Klohn, PC, Rossi, D and Flechsig, E (2002). Transmission of prions. Journal of Infectious Diseases 186 (Suppl. 2): S157–S165.Google Scholar
Wells, GA, Dawson, M, Hawkins, SA, Green, RB, Dexter, I, Francis, ME, Simmons, MM, Austin, AR and Horigan, MW (1994). Infectivity in the ileum of cattle challenged orally with bovine spongiform encephalopathy. Veterinary Record 135: 40–41.Google Scholar
Wickner, RB (1994). [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science 264: 566–569.Google Scholar
Wickner, RB, Taylor, KL, Edskes, HK and Maddelein, ML (2000a). Prions: portable prion domains. Current Biology 10: R335–R337.Google Scholar
Wickner, RB, Taylor, KL, Edskes, HK, Maddelein, ML, Moriyama, H and Roberts, BT (2000b). Prions of yeast as heritable amyloidoses. Journal of Structural Biology 130: 310–322.Google Scholar
Wilesmith, JW, Wells, GA, Cranwell, MP and Ryan, JB (1988). Bovine spongiform encephalopathy: epidemiological studies. Veterinary Record 123: 638–644.Google Scholar
Wilesmith, JW, Ryan, JB and Atkinson, MJ (1991). Bovine spongiform encephalopathy: epidemiological studies on the origin. Veterinary Record 128: 199–203.Google Scholar
Will, RG, Ironside, JW, Zeidler, M, Cousens, SN, Estibeiro, K, Alperovitch, A, Poser, S, Pocchiari, M, Hofman, A and Smith, PG (1996). A new variant of Creutzfeldt–Jakob disease in the UK. Lancet 347: 921–925.Google Scholar
Will, RG, Alperovitch, A, Poser, S, Pocchiari, M, Hofman, A, Mitrova, E, de Silva, R, D'Alessandro, M, Delasnerie-Laupretre, N, Zerr, I and van Duijn, C (1998). Descriptive epidemiology of Creutzfeldt–Jakob disease in six European countries, 1993–1995. EU Collaborative Study Group for CJD. Annals of Neurology 43: 763–767.Google Scholar
Williams, ES and Miller, MW (2002). Chronic wasting disease in deer and elk in North America. Revue Scientifique et Technique (International Office of Epizootics) 21: 305–316.Google Scholar
Williams, ES and Young, S (1980). Chronic wasting disease of captive mule deer: a spongiform encephalopathy. Journal of Wildlife Diseases 16: 89–98.Google Scholar
Williams, ES and Young, S (1982). Spongiform encephalopathy of Rocky Mountain elk. Journal of Wildlife Diseases 18: 465–471.Google Scholar
Williams, ES and Young, S (1992). Spongiform encephalopathies in Cervidae. Revue Scientifique et Technique (International Office of Epizootics). 11: 551–567.Google Scholar
Wineland, NE, Detwiler, LA and Salman, MD (1998). Epidemiologic analysis of reported scrapie in sheep in the United States: 1, 117 cases (1947–1992). Journal of the American Veterinary Medical Association 212: 713–718.Google Scholar
Wyatt, JM, Pearson, GR, Smerdon, TN, Gruffydd-Jones, TJ, Wells, GA and Wilesmith, JW (1991). Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Veterinary Record 129: 233–236.Google Scholar
Yedidia, Y, Horonchik, L, Tzaban, S, Yanai, A and Taraboulos, A (2001). Proteasomes and ubiquitin are involved in the turnover of the wild-type prion protein. EMBO Journal 20: 5383–5391.Google Scholar
Zahn, R, Liu, A, Luhrs, T, Riek, R, von Schroetter, C, Lopez, GF, Billeter, M, Calzolai, L, Wider, G and Wuthrich, K (2000). NMR solution structure of the human prion protein. Proceedings of the National Academy of Sciences of the United States of America 97: 145–150.Google Scholar
Zeiler, B, Adler, V, Kryukov, V and Grossman, A (2003). Concentration and removal of prion proteins from biological solutions. Biotechnology and Applied Biochemistry 37: 173–182.Google Scholar
Zerr, I, Bodemer, M, Racker, S, Grosche, S, Poser, S, Kretzschmar, HA and Weber, T (1995). Cerebrospinal fluid concentration of neuron-specific enolase in diagnosis of Creutzfeldt–Jakob disease. Lancet 345: 1609–1610.Google Scholar
Zerr, I, Bodemer, M, Gefeller, O, Otto, M, Poser, S, Wiltfang, J, Windl, O, Kretzschmar, HA and Weber, T (1998). Detection of 14–3-3 protein in the cerebrospinal fluid supports the diagnosis of Creutzfeldt–Jakob disease. Annals of Neurology 43: 32–40.Google Scholar
Zhou, J, Holtzman, DM, Weiner, RI and Mobley, WC (1994). Expression of TrkA confers neuron-like responsiveness to nerve growth factor on an immortalized hypothalamic cell line. Proceedings of the National Academy of Sciences of the United States of America 91: 3824–3828.Google Scholar
Zou, WQ, Zheng, J, Gray, DM, Gambetti, P and Chen, SG (2004). Antibody to DNA detects scrapie but not normal prion protein. Proceedings of the National Academy of Sciences of the United States of America 101: 1380–1385.Google Scholar