• Keine Ergebnisse gefunden

[1] S.B. Prusiner, Prions, Proc Natl Acad Sci U S A 95 (1998) 13363-13383.

[2] S.B. Prusiner, Shattuck lecture--neurodegenerative diseases and prions, N Engl J Med 344 (2001) 1516-1526.

[3] U. Unterberger, T. Voigtlander, H. Budka, Pathogenesis of prion diseases, Acta Neuropathol 109 (2005) 32-48.

[8] J.S. Griffith, Self-replication and scrapie, Nature 215 (1967) 1043-1044.

[9] S.B. Prusiner, Novel proteinaceous infectious particles cause scrapie, Science 216 (1982) 136-144.

[10] S.B. Prusiner, D.F. Groth, D.C. Bolton, S.B. Kent, L.E. Hood, Purification and structural studies of a major scrapie prion protein, Cell 38 (1984) 127-134.

[11] K.M. Pan, M. Baldwin, J. Nguyen, M. Gasset, A. Serban, D. Groth, I. Mehlhorn, Z. Huang, R.J.

Fletterick, F.E. Cohen, et al., Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins, Proc Natl Acad Sci U S A 90 (1993) 10962-10966.

[12] M.P. McKinley, D.C. Bolton, S.B. Prusiner, A protease-resistant protein is a structural component of the scrapie prion, Cell 35 (1983) 57-62.

[13] E. Rivera-Milla, B. Oidtmann, C.H. Panagiotidis, M. Baier, T. Sklaviadis, R. Hoffmann, Y. Zhou, G.P. Solis, C.A. Stuermer, E. Malaga-Trillo, Disparate evolution of prion protein domains and the distinct origin of Doppel- and prion-related loci revealed by fish-to-mammal comparisons, Faseb J 20 (2006) 317-319.

[14] N. Stahl, D.R. Borchelt, K. Hsiao, S.B. Prusiner, Scrapie prion protein contains a phosphatidylinositol glycolipid, Cell 51 (1987) 229-240.

[15] E. Turk, D.B. Teplow, L.E. Hood, S.B. Prusiner, Purification and properties of the cellular and scrapie hamster prion proteins, European journal of biochemistry / FEBS 176 (1988) 21-30.

[16] T. Haraguchi, S. Fisher, S. Olofsson, T. Endo, D. Groth, A. Tarentino, D.R. Borchelt, D. Teplow, L. Hood, A. Burlingame, et al., Asparagine-linked glycosylation of the scrapie and cellular prion proteins, Arch Biochem Biophys 274 (1989) 1-13.

[17] N. Madore, K.L. Smith, C.H. Graham, A. Jen, K. Brady, S. Hall, R. Morris, Functionally different GPI proteins are organized in different domains on the neuronal surface, Embo J 18 (1999) 6917-6926.

[18] N. Naslavsky, H. Shmeeda, G. Friedlander, A. Yanai, A.H. Futerman, Y. Barenholz, A.

Taraboulos, Sphingolipid depletion increases formation of the scrapie prion protein in neuroblastoma cells infected with prions, J Biol Chem 274 (1999) 20763-20771.

[19] A. Taraboulos, M. Scott, A. Semenov, D. Avrahami, L. Laszlo, S.B. Prusiner, Cholesterol depletion and modification of COOH-terminal targeting sequence of the prion protein inhibit formation of the scrapie isoform, J Cell Biol 129 (1995) 121-132.

[20] C. Sunyach, A. Jen, J. Deng, K.T. Fitzgerald, Y. Frobert, J. Grassi, M.W. McCaffrey, R. Morris, The mechanism of internalization of glycosylphosphatidylinositol-anchored prion protein, Embo J 22 (2003) 3591-3601.

[21] M. Vey, S. Pilkuhn, H. Wille, R. Nixon, S.J. DeArmond, E.J. Smart, R.G. Anderson, A.

Taraboulos, S.B. Prusiner, Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains, Proc Natl Acad Sci U S A 93 (1996) 14945-14949.

[22] V. Campana, D. Sarnataro, C. Zurzolo, The highways and byways of prion protein trafficking, Trends Cell Biol 15 (2005) 102-111.

[23] A.C. Magalhaes, J.A. Silva, K.S. Lee, V.R. Martins, V.F. Prado, S.S. Ferguson, M.V. Gomez, R.R.

Brentani, M.A. Prado, Endocytic intermediates involved with the intracellular trafficking of a fluorescent cellular prion protein, J Biol Chem 277 (2002) 33311-33318.

[24] M.A. Prado, J. Alves-Silva, A.C. Magalhaes, V.F. Prado, R. Linden, V.R. Martins, R.R. Brentani, PrPc on the road: trafficking of the cellular prion protein, J Neurochem 88 (2004) 769-781.

[25] A. Reuter, U. Binkle, C.A. Stuermer, H. Plattner, PrPc and reggies/flotillins are contained in and released via lipid-rich vesicles in Jurkat T cells, Cell Mol Life Sci 61 (2004) 2092-2099.

[26] L.J. Vella, R.A. Sharples, V.A. Lawson, C.L. Masters, R. Cappai, A.F. Hill, Packaging of prions into exosomes is associated with a novel pathway of PrP processing, J Pathol 211 (2007) 582-590.

[27] R. Riek, S. Hornemann, G. Wider, R. Glockshuber, K. Wuthrich, NMR characterization of the full-length recombinant murine prion protein, mPrP(23-231), FEBS Lett 413 (1997) 282-288.

[28] R. Zahn, A. Liu, T. Luhrs, R. Riek, C. von Schroetter, F. Lopez Garcia, M. Billeter, L. Calzolai, G.

Wider, K. Wuthrich, NMR solution structure of the human prion protein, Proc Natl Acad Sci U S A 97 (2000) 145-150.

[29] H. Wille, M.D. Michelitsch, V. Guenebaut, S. Supattapone, A. Serban, F.E. Cohen, D.A. Agard, S.B. Prusiner, Structural studies of the scrapie prion protein by electron crystallography, Proc Natl Acad Sci U S A 99 (2002) 3563-3568.

[30] D. Riesner, Biochemistry and structure of PrP(C) and PrP(Sc), Br Med Bull 66 (2003) 21-33.

[31] C. Govaerts, H. Wille, S.B. Prusiner, F.E. Cohen, Evidence for assembly of prions with left-handed beta-helices into trimers, Proc Natl Acad Sci U S A 101 (2004) 8342-8347.

[32] S. Yang, H. Levine, J.N. Onuchic, D.L. Cox, Structure of infectious prions: stabilization by domain swapping, Faseb J 19 (2005) 1778-1782.

[33] J. Watzlawik, L. Skora, D. Frense, C. Griesinger, M. Zweckstetter, W.J. Schulz-Schaeffer, M.L.

Kramer, Prion protein helix1 promotes aggregation but is not converted into beta -sheet, J Biol Chem (2006).

[34] H. Bueler, M. Fischer, Y. Lang, H. Bluethmann, H.P. Lipp, S.J. DeArmond, S.B. Prusiner, M.

Aguet, C. Weissmann, Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein, Nature 356 (1992) 577-582.

[35] H. Bueler, A. Aguzzi, A. Sailer, R.A. Greiner, P. Autenried, M. Aguet, C. Weissmann, Mice devoid of PrP are resistant to scrapie, Cell 73 (1993) 1339-1347.

[36] J.C. Manson, A.R. Clarke, M.L. Hooper, L. Aitchison, I. McConnell, J. Hope, 129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal, Mol Neurobiol 8 (1994) 121-127.

[37] I. Tobler, S.E. Gaus, T. Deboer, P. Achermann, M. Fischer, T. Rulicke, M. Moser, B. Oesch, P.A.

McBride, J.C. Manson, Altered circadian activity rhythms and sleep in mice devoid of prion protein, Nature 380 (1996) 639-642.

[38] S.B. Colling, J. Collinge, J.G. Jefferys, Hippocampal slices from prion protein null mice:

disrupted Ca(2+)-activated K+ currents, Neurosci Lett 209 (1996) 49-52.

[39] S.B. Colling, M. Khana, J. Collinge, J.G. Jefferys, Mossy fibre reorganization in the hippocampus of prion protein null mice, Brain Res 755 (1997) 28-35.

[40] J. Collinge, M.A. Whittington, K.C. Sidle, C.J. Smith, M.S. Palmer, A.R. Clarke, J.G. Jefferys, Prion protein is necessary for normal synaptic function, Nature 370 (1994) 295-297.

[41] J.C. Manson, J. Hope, A.R. Clarke, A. Johnston, C. Black, N. MacLeod, PrP gene dosage and long term potentiation, Neurodegeneration 4 (1995) 113-114.

[42] M.A. Whittington, K.C. Sidle, I. Gowland, J. Meads, A.F. Hill, M.S. Palmer, J.G. Jefferys, J.

Collinge, Rescue of neurophysiological phenotype seen in PrP null mice by transgene encoding human prion protein, Nature genetics 9 (1995) 197-201.

[43] M. Fuhrmann, T. Bittner, G. Mitteregger, N. Haider, S. Moosmang, H. Kretzschmar, J. Herms, Loss of the cellular prion protein affects the Ca2+ homeostasis in hippocampal CA1 neurons, J Neurochem 98 (2006) 1876-1885.

[44] D.R. Brown, R.S. Nicholas, L. Canevari, Lack of prion protein expression results in a neuronal phenotype sensitive to stress, J Neurosci Res 67 (2002) 211-224.

Literature 124

[45] D.R. Brown, W.J. Schulz-Schaeffer, B. Schmidt, H.A. Kretzschmar, Prion protein-deficient cells show altered response to oxidative stress due to decreased SOD-1 activity, Experimental neurology 146 (1997) 104-112.

[46] F. Klamt, F. Dal-Pizzol, M.J. Conte da Frota, R. Walz, M.E. Andrades, E.G. da Silva, R.R.

Brentani, I. Izquierdo, J.C. Fonseca Moreira, Imbalance of antioxidant defense in mice lacking cellular prion protein, Free radical biology & medicine 30 (2001) 1137-1144.

[47] A.R. White, S.J. Collins, F. Maher, M.F. Jobling, L.R. Stewart, J.M. Thyer, K. Beyreuther, C.L.

Masters, R. Cappai, Prion protein-deficient neurons reveal lower glutathione reductase activity and increased susceptibility to hydrogen peroxide toxicity, Am J Pathol 155 (1999) 1723-1730.

[48] B.S. Wong, T. Liu, R. Li, T. Pan, R.B. Petersen, M.A. Smith, P. Gambetti, G. Perry, J.C. Manson, D.R. Brown, M.S. Sy, Increased levels of oxidative stress markers detected in the brains of mice devoid of prion protein, J Neurochem 76 (2001) 565-572.

[49] A. Li, S. Sakaguchi, R. Atarashi, B.C. Roy, R. Nakaoke, K. Arima, N. Okimura, J. Kopacek, K.

Shigematsu, Identification of a novel gene encoding a PrP-like protein expressed as chimeric transcripts fused to PrP exon 1/2 in ataxic mouse line with a disrupted PrP gene, Cellular and molecular neurobiology 20 (2000) 553-567.

[50] A. Li, S. Sakaguchi, K. Shigematsu, R. Atarashi, B.C. Roy, R. Nakaoke, K. Arima, N. Okimura, J.

Kopacek, S. Katamine, Physiological expression of the gene for PrP-like protein, PrPLP/Dpl, by brain endothelial cells and its ectopic expression in neurons of PrP-deficient mice ataxic due to Purkinje cell degeneration, Am J Pathol 157 (2000) 1447-1452.

[51] R.C. Moore, I.Y. Lee, G.L. Silverman, P.M. Harrison, R. Strome, C. Heinrich, A. Karunaratne, S.H. Pasternak, M.A. Chishti, Y. Liang, P. Mastrangelo, K. Wang, A.F. Smit, S. Katamine, G.A.

Carlson, F.E. Cohen, S.B. Prusiner, D.W. Melton, P. Tremblay, L.E. Hood, D. Westaway, Ataxia in prion protein (PrP)-deficient mice is associated with upregulation of the novel PrP-like protein doppel, J Mol Biol 292 (1999) 797-817.

[52] N. Nishida, P. Tremblay, T. Sugimoto, K. Shigematsu, S. Shirabe, C. Petromilli, S.P. Erpel, R.

Nakaoke, R. Atarashi, T. Houtani, M. Torchia, S. Sakaguchi, S.J. DeArmond, S.B. Prusiner, S.

Katamine, A mouse prion protein transgene rescues mice deficient for the prion protein gene from purkinje cell degeneration and demyelination, Lab Invest 79 (1999) 689-697.

[53] S. Sakaguchi, S. Katamine, N. Nishida, R. Moriuchi, K. Shigematsu, T. Sugimoto, A. Nakatani, Y.

Kataoka, T. Houtani, S. Shirabe, H. Okada, S. Hasegawa, T. Miyamoto, T. Noda, Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene, Nature 380 (1996) 528-531.

[54] B. Krebs, C. Dorner-Ciossek, R. Schmalzbauer, N. Vassallo, J. Herms, H.A. Kretzschmar, Prion protein induced signaling cascades in monocytes, Biochem Biophys Res Commun 340 (2006) 13-22.

[55] S. Mouillet-Richard, M. Ermonval, C. Chebassier, J.L. Laplanche, S. Lehmann, J.M. Launay, O.

Kellermann, Signal transduction through prion protein, Science 289 (2000) 1925-1928.

[56] B. Schneider, V. Mutel, M. Pietri, M. Ermonval, S. Mouillet-Richard, O. Kellermann, NADPH oxidase and extracellular regulated kinases 1/2 are targets of prion protein signaling in neuronal and nonneuronal cells, Proc Natl Acad Sci U S A 100 (2003) 13326-13331.

[57] C. Spielhaupter, H.M. Schatzl, PrPC directly interacts with proteins involved in signaling pathways, J Biol Chem 276 (2001) 44604-44612.

[58] C.A. Stuermer, M.F. Langhorst, M.F. Wiechers, D.F. Legler, S.H. Von Hanwehr, A.H. Guse, H.

Plattner, PrPc capping in T cells promotes its association with the lipid raft proteins reggie-1 and reggie-2 and leads to signal transduction, Faseb J 18 (2004) 1731-1733.

[59] S. Mouillet-Richard, M. Pietri, B. Schneider, C. Vidal, V. Mutel, J.M. Launay, O. Kellermann, Modulation of serotonergic receptor signaling and cross-talk by prion protein, J Biol Chem 280 (2005) 4592-4601.

[60] J. Weise, R. Sandau, S. Schwarting, O. Crome, A. Wrede, W. Schulz-Schaeffer, I. Zerr, M. Bahr, Deletion of cellular prion protein results in reduced Akt activation, enhanced postischemic

caspase-3 activation, and exacerbation of ischemic brain injury, Stroke; a journal of cerebral circulation 37 (2006) 1296-1300.

[61] N. Vassallo, J. Herms, C. Behrens, B. Krebs, K. Saeki, T. Onodera, O. Windl, H.A. Kretzschmar, Activation of phosphatidylinositol 3-kinase by cellular prion protein and its role in cell survival, Biochem Biophys Res Commun 332 (2005) 75-82.

[62] L.B. Chiarini, A.R. Freitas, S.M. Zanata, R.R. Brentani, V.R. Martins, R. Linden, Cellular prion protein transduces neuroprotective signals, Embo J 21 (2002) 3317-3326.

[63] S.M. Zanata, M.H. Lopes, A.F. Mercadante, G.N. Hajj, L.B. Chiarini, R. Nomizo, A.R. Freitas, A.L. Cabral, K.S. Lee, M.A. Juliano, E. de Oliveira, S.G. Jachieri, A. Burlingame, L. Huang, R.

Linden, R.R. Brentani, V.R. Martins, Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection, Embo J 21 (2002) 3307-3316.

[64] M.H. Lopes, G.N. Hajj, A.G. Muras, G.L. Mancini, R.M. Castro, K.C. Ribeiro, R.R. Brentani, R.

Linden, V.R. Martins, Interaction of cellular prion and stress-inducible protein 1 promotes neuritogenesis and neuroprotection by distinct signaling pathways, J Neurosci 25 (2005) 11330-11339.

[65] A. Santuccione, V. Sytnyk, I. Leshchyns'ka, M. Schachner, Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth, J Cell Biol 169 (2005) 341-354.

[66] G. Schmitt-Ulms, G. Legname, M.A. Baldwin, H.L. Ball, N. Bradon, P.J. Bosque, K.L. Crossin, G.M. Edelman, S.J. DeArmond, F.E. Cohen, S.B. Prusiner, Binding of neural cell adhesion molecules (N-CAMs) to the cellular prion protein, J Mol Biol 314 (2001) 1209-1225.

[67] E. Graner, A.F. Mercadante, S.M. Zanata, O.V. Forlenza, A.L. Cabral, S.S. Veiga, M.A. Juliano, R. Roesler, R. Walz, A. Minetti, I. Izquierdo, V.R. Martins, R.R. Brentani, Cellular prion protein binds laminin and mediates neuritogenesis, Brain research 76 (2000) 85-92.

[68] A. Mange, O. Milhavet, D. Umlauf, D. Harris, S. Lehmann, PrP-dependent cell adhesion in N2a neuroblastoma cells, FEBS Lett 514 (2002) 159-162.

[69] O. Milhavet, S. Lehmann, Oxidative stress and the prion protein in transmissible spongiform encephalopathies, Brain research 38 (2002) 328-339.

[70] D.R. Brown, B. Schmidt, H.A. Kretzschmar, Effects of oxidative stress on prion protein expression in PC12 cells, Int J Dev Neurosci 15 (1997) 961-972.

[71] D.R. Brown, A. Besinger, Prion protein expression and superoxide dismutase activity, Biochem J 334 ( Pt 2) (1998) 423-429.

[72] D.R. Brown, B.S. Wong, F. Hafiz, C. Clive, S.J. Haswell, I.M. Jones, Normal prion protein has an activity like that of superoxide dismutase, Biochem J 344 Pt 1 (1999) 1-5.

[73] T.D. Rae, P.J. Schmidt, R.A. Pufahl, V.C. Culotta, T.V. O'Halloran, Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase, Science 284 (1999) 805-808.

[74] S. Jones, M. Batchelor, D. Bhelt, A.R. Clarke, J. Collinge, G.S. Jackson, Recombinant prion protein does not possess SOD-1 activity, Biochem J 392 (2005) 309-312.

[75] D.R. Brown, K. Qin, J.W. Herms, A. Madlung, J. Manson, R. Strome, P.E. Fraser, T. Kruck, A.

von Bohlen, W. Schulz-Schaeffer, A. Giese, D. Westaway, H. Kretzschmar, The cellular prion protein binds copper in vivo, Nature 390 (1997) 684-687.

[76] G.S. Jackson, I. Murray, L.L. Hosszu, N. Gibbs, J.P. Waltho, A.R. Clarke, J. Collinge, Location and properties of metal-binding sites on the human prion protein, Proc Natl Acad Sci U S A 98 (2001) 8531-8535.

[77] M.L. Kramer, H.D. Kratzin, B. Schmidt, A. Romer, O. Windl, S. Liemann, S. Hornemann, H.

Kretzschmar, Prion protein binds copper within the physiological concentration range, J Biol Chem 276 (2001) 16711-16719.

[78] J. Stockel, J. Safar, A.C. Wallace, F.E. Cohen, S.B. Prusiner, Prion protein selectively binds copper(II) ions, Biochemistry 37 (1998) 7185-7193.

[79] L.R. Brown, D.A. Harris, Copper and zinc cause delivery of the prion protein from the plasma membrane to a subset of early endosomes and the Golgi, J Neurochem 87 (2003) 353-363.

Literature 126

[80] P.C. Pauly, D.A. Harris, Copper stimulates endocytosis of the prion protein, J Biol Chem 273 (1998) 33107-33110.

[81] W.S. Perera, N.M. Hooper, Ablation of the metal ion-induced endocytosis of the prion protein by disease-associated mutation of the octarepeat region, Curr Biol 11 (2001) 519-523.

[82] D.R. Brown, Prion and prejudice: normal protein and the synapse, Trends Neurosci 24 (2001) 85-90.

[83] D.R. Brown, C. Clive, S.J. Haswell, Antioxidant activity related to copper binding of native prion protein, J Neurochem 76 (2001) 69-76.

[84] S. Barmada, P. Piccardo, K. Yamaguchi, B. Ghetti, D.A. Harris, GFP-tagged prion protein is correctly localized and functionally active in the brains of transgenic mice, Neurobiol Dis 16 (2004) 527-537.

[85] M.J. Ford, L.J. Burton, H. Li, C.H. Graham, Y. Frobert, J. Grassi, S.M. Hall, R.J. Morris, A marked disparity between the expression of prion protein and its message by neurones of the CNS, Neuroscience 111 (2002) 533-551.

[86] J. Laine, M.E. Marc, M.S. Sy, H. Axelrad, Cellular and subcellular morphological localization of normal prion protein in rodent cerebellum, Eur J Neurosci 14 (2001) 47-56.

[87] A. Mironov, Jr., D. Latawiec, H. Wille, E. Bouzamondo-Bernstein, G. Legname, R.A.

Williamson, D. Burton, S.J. DeArmond, S.B. Prusiner, P.J. Peters, Cytosolic prion protein in neurons, J Neurosci 23 (2003) 7183-7193.

[88] K.L. Moya, R. Hassig, C. Creminon, I. Laffont, L. Di Giamberardino, Enhanced detection and retrograde axonal transport of PrPc in peripheral nerve, J Neurochem 88 (2004) 155-160.

[89] K.L. Moya, N. Sales, R. Hassig, C. Creminon, J. Grassi, L. Di Giamberardino, Immunolocalization of the cellular prion protein in normal brain, Microsc Res Tech 50 (2000) 58-65.

[90] N. Sales, R. Hassig, K. Rodolfo, L. Di Giamberardino, E. Traiffort, M. Ruat, P. Fretier, K.L. Moya, Developmental expression of the cellular prion protein in elongating axons, Eur J Neurosci 15 (2002) 1163-1177.

[91] D.R. Borchelt, V.E. Koliatsos, M. Guarnieri, C.A. Pardo, S.S. Sisodia, D.L. Price, Rapid anterograde axonal transport of the cellular prion glycoprotein in the peripheral and central nervous systems, J Biol Chem 269 (1994) 14711-14714.

[92] J. Kanaani, S.B. Prusiner, J. Diacovo, S. Baekkeskov, G. Legname, Recombinant prion protein induces rapid polarization and development of synapses in embryonic rat hippocampal neurons in vitro, J Neurochem 95 (2005) 1373-1386.

[93] A. Carleton, P. Tremblay, J.D. Vincent, P.M. Lledo, Dose-dependent, prion protein (PrP)-mediated facilitation of excitatory synaptic transmission in the mouse hippocampus, Pflugers Arch 442 (2001) 223-229.

[94] J.R. Criado, M. Sanchez-Alavez, B. Conti, J.L. Giacchino, D.N. Wills, S.J. Henriksen, R. Race, J.C.

Manson, B. Chesebro, M.B. Oldstone, Mice devoid of prion protein have cognitive deficits that are rescued by reconstitution of PrP in neurons, Neurobiol Dis 19 (2005) 255-265.

[95] Y. Bounhar, Y. Zhang, C.G. Goodyer, A. LeBlanc, Prion protein protects human neurons against Bax-mediated apoptosis, J Biol Chem 276 (2001) 39145-39149.

[96] X. Roucou, P.N. Giannopoulos, Y. Zhang, J. Jodoin, C.G. Goodyer, A. LeBlanc, Cellular prion protein inhibits proapoptotic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells, Cell Death Differ 12 (2005) 783-795.

[97] X. Roucou, Q. Guo, Y. Zhang, C.G. Goodyer, A.C. LeBlanc, Cytosolic prion protein is not toxic and protects against Bax-mediated cell death in human primary neurons, J Biol Chem 278 (2003) 40877-40881.

[98] C. Kuwahara, A.M. Takeuchi, T. Nishimura, K. Haraguchi, A. Kubosaki, Y. Matsumoto, K. Saeki, Y. Matsumoto, T. Yokoyama, S. Itohara, T. Onodera, Prions prevent neuronal cell-line death, Nature 400 (1999) 225-226.

[99] A. Sakudo, D.C. Lee, K. Saeki, Y. Nakamura, K. Inoue, Y. Matsumoto, S. Itohara, T. Onodera, Impairment of superoxide dismutase activation by N-terminally truncated prion protein (PrP) in PrP-deficient neuronal cell line, Biochem Biophys Res Commun 308 (2003) 660-667.

[100] M. Diarra-Mehrpour, S. Arrabal, A. Jalil, X. Pinson, C. Gaudin, G. Pietu, A. Pitaval, H. Ripoche, M. Eloit, D. Dormont, S. Chouaib, Prion protein prevents human breast carcinoma cell line from tumor necrosis factor alpha-induced cell death, Cancer research 64 (2004) 719-727.

[101] B. Drisaldi, J. Coomaraswamy, P. Mastrangelo, B. Strome, J. Yang, J.C. Watts, M.A. Chishti, M.

Marvi, O. Windl, R. Ahrens, F. Major, M.S. Sy, H. Kretzschmar, P.E. Fraser, H.T. Mount, D.

Westaway, Genetic mapping of activity determinants within cellular prion proteins: N-terminal modules in PrPC offset pro-apoptotic activity of the Doppel helix B/B' region, J Biol Chem 279 (2004) 55443-55454.

[102] K. Qin, L. Zhao, Y. Tang, S. Bhatta, J.M. Simard, R.Y. Zhao, Doppel-induced apoptosis and counteraction by cellular prion protein in neuroblastoma and astrocytes, Neuroscience 141 (2006) 1375-1388.

[103] E. Paitel, C. Alves da Costa, D. Vilette, J. Grassi, F. Checler, Overexpression of PrPc triggers caspase 3 activation: potentiation by proteasome inhibitors and blockade by anti-PrP antibodies, J Neurochem 83 (2002) 1208-1214.

[104] E. Paitel, R. Fahraeus, F. Checler, Cellular prion protein sensitizes neurons to apoptotic stimuli through Mdm2-regulated and p53-dependent caspase 3-like activation, J Biol Chem 278 (2003) 10061-10066.

[105] E. Paitel, C. Sunyach, C. Alves da Costa, J.C. Bourdon, B. Vincent, F. Checler, Primary cultured neurons devoid of cellular prion display lower responsiveness to staurosporine through the control of p53 at both transcriptional and post-transcriptional levels, J Biol Chem 279 (2004) 612-618.

[106] L. Westergard, H.M. Christensen, D.A. Harris, The cellular prion protein (PrP(C)): its physiological function and role in disease, Biochim Biophys Acta 1772 (2007) 629-644.

[107] V. Zomosa-Signoret, J.D. Arnaud, P. Fontes, M.T. Alvarez-Martinez, J.P. Liautard, Physiological role of the cellular prion protein, Vet Res 39 (2008) 9.

[108] S. Brandner, S. Isenmann, A. Raeber, M. Fischer, A. Sailer, Y. Kobayashi, S. Marino, C.

Weissmann, A. Aguzzi, Normal host prion protein necessary for scrapie-induced neurotoxicity, Nature 379 (1996) 339-343.

[109] G. Mallucci, A. Dickinson, J. Linehan, P.C. Klohn, S. Brandner, J. Collinge, Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis, Science 302 (2003) 871-874.

[110] D.R. Brown, J. Herms, H.A. Kretzschmar, Mouse cortical cells lacking cellular PrP survive in culture with a neurotoxic PrP fragment, Neuroreport 5 (1994) 2057-2060.

[111] B. Chesebro, M. Trifilo, R. Race, K. Meade-White, C. Teng, R. LaCasse, L. Raymond, C. Favara, G. Baron, S. Priola, B. Caughey, E. Masliah, M. Oldstone, Anchorless prion protein results in infectious amyloid disease without clinical scrapie, Science 308 (2005) 1435-1439.

[112] L. Solforosi, J.R. Criado, D.B. McGavern, S. Wirz, M. Sanchez-Alavez, S. Sugama, L.A.

DeGiorgio, B.T. Volpe, E. Wiseman, G. Abalos, E. Masliah, D. Gilden, M.B. Oldstone, B. Conti, R.A. Williamson, Cross-linking cellular prion protein triggers neuronal apoptosis in vivo, Science 303 (2004) 1514-1516.

[113] A. Li, H.M. Christensen, L.R. Stewart, K.A. Roth, R. Chiesa, D.A. Harris, Neonatal lethality in transgenic mice expressing prion protein with a deletion of residues 105-125, Embo J 26 (2007) 548-558.

[114] A. Behrens, A. Aguzzi, Small is not beautiful: antagonizing functions for the prion protein PrP(C) and its homologue Dpl, Trends Neurosci 25 (2002) 150-154.

[115] R. Chiesa, D.A. Harris, Prion diseases: what is the neurotoxic molecule?, Neurobiol Dis 8 (2001) 743-763.

[116] B. Caughey, G.S. Baron, Prions and their partners in crime, Nature 443 (2006) 803-810.

[117] D.A. Harris, H.L. True, New insights into prion structure and toxicity, Neuron 50 (2006) 353-357.

Literature 128

[118] D.R. Borchelt, A. Taraboulos, S.B. Prusiner, Evidence for synthesis of scrapie prion proteins in the endocytic pathway, J Biol Chem 267 (1992) 16188-16199.

[119] B. Caughey, G.J. Raymond, The scrapie-associated form of PrP is made from a cell surface precursor that is both protease- and phospholipase-sensitive, J Biol Chem 266 (1991) 18217-18223.

[120] S. Gilch, K.F. Winklhofer, M.H. Groschup, M. Nunziante, R. Lucassen, C. Spielhaupter, W.

Muranyi, D. Riesner, J. Tatzelt, H.M. Schatzl, Intracellular re-routing of prion protein prevents propagation of PrP(Sc) and delays onset of prion disease, Embo J 20 (2001) 3957-3966.

[121] K. Kaneko, M. Vey, M. Scott, S. Pilkuhn, F.E. Cohen, S.B. Prusiner, COOH-terminal sequence of the cellular prion protein directs subcellular trafficking and controls conversion into the scrapie isoform, Proc Natl Acad Sci U S A 94 (1997) 2333-2338.

[122] A. Taraboulos, A.J. Raeber, D.R. Borchelt, D. Serban, S.B. Prusiner, Synthesis and trafficking of prion proteins in cultured cells, Mol Biol Cell 3 (1992) 851-863.

[123] B. Caughey, G.J. Raymond, D. Ernst, R.E. Race, 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 (1991) 6597-6603.

[124] F. Beranger, A. Mange, B. Goud, S. Lehmann, Stimulation of PrP(C) retrograde transport toward the endoplasmic reticulum increases accumulation of PrP(Sc) in prion-infected cells, J Biol Chem 277 (2002) 38972-38977.

[125] G.S. Baron, B. Caughey, Effect of glycosylphosphatidylinositol anchordependent and -independent prion protein association with model raft membranes on conversion to the protease-resistant isoform, J Biol Chem 278 (2003) 14883-14892.

[126] G.S. Baron, K. Wehrly, D.W. Dorward, B. Chesebro, B. Caughey, Conversion of raft associated prion protein to the protease-resistant state requires insertion of PrP-res (PrP(Sc)) into contiguous membranes, Embo J 21 (2002) 1031-1040.

[127] L. Botto, M. Masserini, A. Cassetti, P. Palestini, Immunoseparation of Prion protein-enriched domains from other detergent-resistant membrane fractions, isolated from neuronal cells, FEBS Lett 557 (2004) 143-147.

[128] N. Naslavsky, R. Stein, A. Yanai, G. Friedlander, A. Taraboulos, Characterization of detergent-insoluble complexes containing the cellular prion protein and its scrapie isoform, J Biol Chem 272 (1997) 6324-6331.

[129] A. Mange, N. Nishida, O. Milhavet, H.E. McMahon, D. Casanova, S. Lehmann, Amphotericin B inhibits the generation of the scrapie isoform of the prion protein in infected cultures, J Virol 74 (2000) 3135-3140.

[130] M. Marella, S. Lehmann, J. Grassi, J. Chabry, Filipin prevents pathological prion protein accumulation by reducing endocytosis and inducing cellular PrP release, J Biol Chem 277 (2002) 25457-25464.

[131] M.P. McKinley, A. Taraboulos, L. Kenaga, D. Serban, A. Stieber, S.J. DeArmond, S.B. Prusiner, N. Gonatas, Ultrastructural localization of scrapie prion proteins in cytoplasmic vesicles of infected cultured cells, Lab Invest 65 (1991) 622-630.

[132] M. Kristiansen, P. Deriziotis, D.E. Dimcheff, G.S. Jackson, H. Ovaa, H. Naumann, A.R. Clarke, F.W. van Leeuwen, V. Menendez-Benito, N.P. Dantuma, J.L. Portis, J. Collinge, S.J. Tabrizi, Disease-associated prion protein oligomers inhibit the 26S proteasome, Mol Cell 26 (2007) 175-188.

[133] F. Pimpinelli, S. Lehmann, I. Maridonneau-Parini, The scrapie prion protein is present in flotillin-1-positive vesicles in central- but not peripheral-derived neuronal cell lines, Eur J Neurosci 21 (2005) 2063-2072.

[134] A. Taraboulos, D. Serban, S.B. Prusiner, Scrapie prion proteins accumulate in the cytoplasm of persistently infected cultured cells, J Cell Biol 110 (1990) 2117-2132.

[135] D.R. Borchelt, M. Scott, A. Taraboulos, N. Stahl, S.B. Prusiner, Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells, J Cell Biol 110 (1990) 743-752.

[136] B. Fevrier, D. Vilette, F. Archer, D. Loew, W. Faigle, M. Vidal, H. Laude, G. Raposo, Cells release prions in association with exosomes, Proc Natl Acad Sci U S A 101 (2004) 9683-9688.

[137] A. Mange, C. Crozet, S. Lehmann, F. Beranger, Scrapie-like prion protein is translocated to the nuclei of infected cells independently of proteasome inhibition and interacts with chromatin, J Cell Sci 117 (2004) 2411-2416.

[138] M. Kristiansen, M.J. Messenger, P.C. Klohn, S. Brandner, J.D. Wadsworth, J. Collinge, S.J.

Tabrizi, Disease-related prion protein forms aggresomes in neuronal cells leading to caspase activation and apoptosis, J Biol Chem 280 (2005) 38851-38861.

[139] J.G. Fournier, F. Escaig-Haye, V. Grigoriev, Ultrastructural localization of prion proteins:

physiological and pathological implications, Microsc Res Tech 50 (2000) 76-88.

[140] V. Grigoriev, F. Escaig-Haye, N. Streichenberger, N. Kopp, J. Langeveld, P. Brown, J.G.

Fournier, Submicroscopic immunodetection of PrP in the brain of a patient with a new-variant of Creutzfeldt-Jakob disease, Neurosci Lett 264 (1999) 57-60.

[141] L. Laszlo, J. Lowe, T. Self, N. Kenward, M. Landon, T. McBride, C. Farquhar, I. McConnell, J.

Brown, J. Hope, et al., Lysosomes as key organelles in the pathogenesis of prion encephalopathies, J Pathol 166 (1992) 333-341.

[142] J. Lowe, J. Fergusson, N. Kenward, L. Laszlo, M. Landon, C. Farquhar, J. Brown, J. Hope, R.J.

Mayer, Immunoreactivity to ubiquitin-protein conjugates is present early in the disease process in the brains of scrapie-infected mice, J Pathol 168 (1992) 169-177.

[143] R.J. Mayer, M. Landon, L. Laszlo, G. Lennox, J. Lowe, Protein processing in lysosomes: the new therapeutic target in neurodegenerative disease, Lancet 340 (1992) 156-159.

[144] G.G. Kovacs, E. Gelpi, T. Strobel, G. Ricken, J.R. Nyengaard, H. Bernheimer, H. Budka, Involvement of the endosomal-lysosomal system correlates with regional pathology in Creutzfeldt-Jakob disease, J Neuropathol Exp Neurol 66 (2007) 628-636.

[145] G.G. Kovacs, M. Preusser, M. Strohschneider, H. Budka, Subcellular localization of disease-associated prion protein in the human brain, Am J Pathol 166 (2005) 287-294.

[146] J.E. Arnold, C. Tipler, L. Laszlo, J. Hope, M. Landon, R.J. Mayer, The abnormal isoform of the prion protein accumulates in late-endosome-like organelles in scrapie-infected mouse brain, J Pathol 176 (1995) 403-411.

[147] M. Jeffrey, C.M. Goodsir, M. Bruce, P.A. McBride, J.R. Scott, W.G. Halliday, Correlative light and electron microscopy studies of PrP localisation in 87V scrapie, Brain Res 656 (1994) 329-343.

[150] E. Paramithiotis, M. Pinard, T. Lawton, S. LaBoissiere, V.L. Leathers, W.Q. Zou, L.A. Estey, J.

Lamontagne, M.T. Lehto, L.H. Kondejewski, G.P. Francoeur, M. Papadopoulos, A. Haghighat, S.J. Spatz, M. Head, R. Will, J. Ironside, K. O'Rourke, Q. Tonelli, H.C. Ledebur, A. Chakrabartty, N.R. Cashman, A prion protein epitope selective for the pathologically misfolded conformation, Nat Med 9 (2003) 893-899.

[151] V. Curin Serbec, M. Bresjanac, M. Popovic, K. Pretnar Hartman, V. Galvani, R. Rupreht, M.

Cernilec, T. Vranac, I. Hafner, R. Jerala, Monoclonal antibody against a peptide of human prion protein discriminates between Creutzfeldt-Jacob's disease-affected and normal brain tissue, J Biol Chem 279 (2004) 3694-3698.

[152] L. Solforosi, A. Bellon, M. Schaller, J.T. Cruite, G.C. Abalos, R.A. Williamson, Toward molecular

[152] L. Solforosi, A. Bellon, M. Schaller, J.T. Cruite, G.C. Abalos, R.A. Williamson, Toward molecular