The Elusive Role of the Prion Protein and the Mechanism of Toxicity in Prion Disease

1. Malaga-Trillo E, Solis GP, Schrock Y, Geiss C, Luncz L, et al. (2009) Regulation of embryonic cell adhesion by the prion protein. PLoS Biol 7: e55. doi: 10.1371/journal.pbio.1000055 19278297

2. Chiesa R, Harris DA (2009) Fishing for prion protein function. PLoS Biol 7: e75. doi: 10.1371/journal.pbio.1000075 19338390

3. Steele AD, Lindquist S, Aguzzi A (2007) The prion protein knockout mouse: a phenotype under challenge. Prion 1 : 83–93. 19164918

4. Linden R, Martins VR, Prado MA, Cammarota M, Izquierdo I, et al. (2008) Physiology of the prion protein. Physiol Rev 88 : 673–728. doi: 10.1152/physrev.00007.2007 18391177

5. Khosravani H, Zhang Y, Tsutsui S, Hameed S, Altier C, et al. (2008) Prion protein attenuates excitotoxicity by inhibiting NMDA receptors. J Cell Biol 181 : 551–565. doi: 10.1083/jcb.200711002 18443219

6. Senatore A, Colleoni S, Verderio C, Restelli E, Morini R, et al. (2012) Mutant PrP suppresses glutamatergic neurotransmission in cerebellar granule neurons by impairing membrane delivery of VGCC α2δ-1 subunit. Neuron 74 : 300–313. doi: 10.1016/j.neuron.2012.02.027 22542184

7. Bueler H, Aguzzi A, Sailer A, Greiner RA, Autenried P, et al. (1993) Mice devoid of PrP are resistant to scrapie. Cell 73 : 1339–1347. 8100741

8. Brandner S, Isenmann S, Raeber A, Fischer M, Sailer A, et al. (1996) Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature 379 : 339–343. 8552188

9. Mallucci G, Dickinson A, Linehan J, Klohn PC, Brandner S, et al. (2003) Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science 302 : 871–874. 14593181

10. Chesebro B, Trifilo M, Race R, Meade-White K, Teng C, et al. (2005) Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science 308 : 1435–1439. 15933194

11. Chesebro B, Race B, Meade-White K, Lacasse R, Race R, et al. (2010) Fatal transmissible amyloid encephalopathy: a new type of prion disease associated with lack of prion protein membrane anchoring. PLoS Pathog 6: e1000800. doi: 10.1371/journal.ppat.1000800 20221436

12. Baumann F, Tolnay M, Brabeck C, Pahnke J, Kloz U, et al. (2007) Lethal recessive myelin toxicity of prion protein lacking its central domain. Embo J 26 : 538–547. 17245436

13. Li A, Christensen HM, Stewart LR, Roth KA, Chiesa R, et al. (2007) Neonatal lethality in transgenic mice expressing prion protein with a deletion of residues 105–125. Embo J 26 : 548–558. 17245437

14. Biasini E, Unterberger U, Solomon IH, Massignan T, Senatore A, et al. (2013) A mutant prion protein sensitizes neurons to glutamate-induced excitotoxicity. J Neurosci 33 : 2408–2418. doi: 10.1523/JNEUROSCI.3406-12.2013 23392670

15. Solomon IH, Khatri N, Biasini E, Massignan T, Huettner JE, et al. (2011) An N-terminal polybasic domain and cell surface localization are required for mutant prion protein toxicity. J Biol Chem 286 : 14724–14736. doi: 10.1074/jbc.M110.214973 21385869

16. Sonati T, Reimann RR, Falsig J, Baral PK, O'Connor T, et al. (2013) The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein. Nature 501 : 102–106. doi: 10.1038/nature12402 23903654

17. Muller WE, Ushijima H, Schroder HC, Forrest JM, Schatton WF, et al. (1993) Cytoprotective effect of NMDA receptor antagonists on prion protein (PrionSc)-induced toxicity in rat cortical cell cultures. Eur J Pharmacol 246 : 261–267. 7901042

18. Resenberger UK, Harmeier A, Woerner AC, Goodman JL, Muller V, et al. (2011) The cellular prion protein mediates neurotoxic signalling of β-sheet-rich conformers independent of prion replication. EMBO J 30 : 2057–2070. doi: 10.1038/emboj.2011.86 21441896

19. Moreno JA, Radford H, Peretti D, Steinert JR, Verity N, et al. (2012) Sustained translational repression by eIF2αα-P mediates prion neurodegeneration. Nature 485 : 507–511. doi: 10.1038/nature11058 22622579

20. Hegde RS, Tremblay P, Groth D, DeArmond SJ, Prusiner SB, et al. (1999) Transmissible and genetic prion diseases share a common pathway of neurodegeneration. Nature 402 : 822–826. 10617204

21. Chiesa R, Piccardo P, Ghetti B, Harris DA (1998) Neurological illness in transgenic mice expressing a prion protein with an insertional mutation. Neuron 21 : 1339–1351. 9883727

22. Dossena S, Imeri L, Mangieri M, Garofoli A, Ferrari L, et al. (2008) Mutant prion protein expression causes motor and memory deficits and abnormal sleep patterns in a transgenic mouse model. Neuron 60 : 598–609. doi: 10.1016/j.neuron.2008.09.008 19038218

23. Bouybayoune I, Mantovani S, Del Gallo F, Bertani I, Restelli E, et al. (2015) Transgenic fatal familial insomnia mice indicate prion infectivity-independent mechanisms of pathogenesis and phenotypic expression of disease. PLoS Path 11: e1004796.

24. Quaglio E, Restelli E, Garofoli A, Dossena S, De Luigi A, et al. (2011) Expression of mutant or cytosolic PrP in transgenic mice and cells is not associated with endoplasmic reticulum stress or proteasome dysfunction. PLoS One 6: e19339. doi: 10.1371/journal.pone.0019339 21559407

25. Senatore A, Restelli E, Chiesa R (2013) Synaptic dysfunction in prion diseases: a trafficking problem? Int J Cell Biol 2013 : 543803. doi: 10.1155/2013/543803 24369467

26. Tateishi J, Kitamoto T (1995) Inherited prion diseases and transmission to rodents. Brain Pathol 5 : 53–59. 7767491

27. Mead S, Gandhi S, Beck J, Caine D, Gajulapalli D, et al. (2013) A novel prion disease associated with diarrhea and autonomic neuropathy. N Engl J Med 369 : 1904–1914. doi: 10.1056/NEJMoa1214747 24224623

28. Diack AB, Ritchie DL, Peden AH, Brown D, Boyle A, et al. (2014) Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties. Emerg Infect Dis 20 : 1969–1979. doi: 10.3201/eid2012.140214 25418327

29. Li J, Browning S, Mahal SP, Oelschlegel AM, Weissmann C (2010) Darwinian evolution of prions in cell culture. Science 327 : 869–872. doi: 10.1126/science.1183218 20044542

30. Berry DB, Lu D, Geva M, Watts JC, Bhardwaj S, et al. (2013) Drug resistance confounding prion therapeutics. Proc Natl Acad Sci U S A 110: E4160–4169. doi: 10.1073/pnas.1317164110 24128760