Proteomics analysis of amyloid and nonamyloid prion disease phenotypes reveals both common and divergent mechanisms of neuropathogenesis

Journal of Proteome Research

Volumn 13, Issue 11, 2014, Pages 4620-4634

  Moore, Roger A ^a   Sturdevant, Dan E ^b   Chesebro, Bruce ^a   Priola, Suzette A ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

^b NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

Alzheimers disease; amyloid; cerebral amyloid angiopathy; glycosylphosphatidylinositol; LC MS MS; prion disease; proteomics; transmissible spongiform encephalopathies

Indexed keywords

AMYLOID; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORED PROTEIN; PRION PROTEIN; CALCIUM;

AMYLOID PLAQUE; AMYLOID PRION DISEASE; ANIMAL EXPERIMENT; APOPTOSIS; ARTICLE; BRAIN HOMOGENATE; BRAIN SPONGIOSIS; CALCIUM HOMEOSTASIS; CELL DEATH; CELL MEMBRANE; COMPLEMENT ACTIVATION; CONTROLLED STUDY; GRAY MATTER; METAL BINDING; MOUSE; NEUROPATHOLOGY; NONAMYLOID PRION DISEASE; NONHUMAN; PHENOTYPE; PRION DISEASE; PROTEOMICS; SIGNAL TRANSDUCTION; SYNAPSE VESICLE; ANIMAL; C57BL MOUSE; GENETICS; HOMEOSTASIS; IMMUNOHISTOCHEMISTRY; LIQUID CHROMATOGRAPHY; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; PROCEDURES; TANDEM MASS SPECTROMETRY; WESTERN BLOTTING;

AMYLOID; ANIMALS; APOPTOSIS; BLOTTING, WESTERN; CALCIUM; CELL MEMBRANE; CHROMATOGRAPHY, LIQUID; HOMEOSTASIS; IMMUNOHISTOCHEMISTRY; MICE; MICE, INBRED C57BL; PHENOTYPE; PRION DISEASES; PROTEOMICS; TANDEM MASS SPECTROMETRY;

EID: 84908884094     PISSN: 15353893     EISSN: 15353907     Source Type: Journal    
DOI: 10.1021/pr500329w     Document Type: Article

References (83)

1. Chesebro, B. Introduction to the Transmissible Spongiform Encephalopathies or Prion Diseases Br. Med. Bull. 2003, 66, 1-20
2. Caughey, B. W.; Dong, A.; Bhat, K. S.; Ernst, D.; Hayes, S. F.; Caughey, W. S. Secondary Structure-Analysis of the Scrapie-Associated Protein Prp 27-30 in Water by Infrared-Spectroscopy Biochemistry 1991, 30, 7672-7680
3. Pan, K.-M.; Baldwin, M.; Nguyen, J.; Gasset, M.; Serban, A.; Groth, D.; Mehlhorn, I.; Huang, Z.; Fletterick, R. J.; Cohen, F. E.; Prusiner, S. B. Conversion of Alpha-Helices into Beta-Sheets Features in the Formation of the Scrapie Prion Protein Proc. Natl. Acad. Sci. U. S. A. 1993, 90, 10962-10966
4. Bruce, M. E. TSE Strain Variation Br. Med. Bull. 2003, 66, 99-108
5. Kretzschmar, H.; Tatzelt, J. Prion Disease: a Tale of Folds and Strains Brain Pathol. 2013, 23, 321-332
6. Poggiolini, I.; Saverioni, D.; Parchi, P. Prion Protein Misfolding, Strains, and Neurotoxicity: An Update From Studies on Mammalian Prions Int. J. Cell Biol. 2013, 2013, 910314
7. Moore, R. A.; Taubner, L. M.; Priola, S. A. Prion Protein Misfolding and Disease Curr. Opin. Struct. Biol. 2009, 19, 14-22
8. Wiltzius, J. J.; Landau, M.; Nelson, R.; Sawaya, M. R.; Apostol, M. I.; Goldschmidt, L.; Soriaga, A. B.; Cascio, D.; Rajashankar, K.; Eisenberg, D. Molecular Mechanisms for Protein-Encoded Inheritance Nat. Struct. Mol. Biol. 2009, 16, 973-978
9. Chesebro, B.; Race, B.; Meade-White, K.; LaCasse, R.; Race, R.; Klingeborn, M.; Striebel, J.; Dorward, D.; McGovern, G.; Jeffrey, M. Fatal Transmissible Amyloid Encephalopathy: a New Type of Prion Disease Associated With Lack of Prion Protein Membrane Anchoring PLoS Pathog. 2010, 6, e1000800
10. Klingeborn, M.; Race, B.; Meade-White, K. D.; Rosenke, R.; Striebel, J. F.; Chesebro, B. Crucial Role for Prion Protein Membrane Anchoring in the Neuroinvasion and Neural Spread of Prion Infection J. Virol. 2011, 85, 1484-1494
11. 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.; Oldstone, M. Anchorless Prion Protein Results in Infectious Amyloid Disease Without Clinical Scrapie Science 2005, 308, 1435-1439
12. Stahl, N.; Borchelt, D. R.; Hsiao, K.; Prusiner, S. B. Scrapie Prion Protein Contains a Phosphatidylinositol Glycolipid Cell 1987, 51, 229-240
13. Ghetti, B.; Piccardo, P.; Spillantini, M. G.; Ichimiya, Y.; Porro, M.; Perini, F.; Kitamoto, T.; Tateishi, J.; Seiler, C.; Frangione, B.; Bugiani, O.; Giaccone, G.; Prelli, F.; Goedert, M.; Dlouhy, S. R.; Tagliavini, F. Vascular Variant of Prion Protein Cerebral Amyloidosis With Tau-Positive Neurofibrillary Tangles: the Phenotype of the Stop Codon 145 Mutation in PRNP Proc. Natl. Acad. Sci. U. S. A. 1996, 93, 744-748
14. Jansen, C.; Parchi, P.; Capellari, S.; Vermeij, A. J.; Corrado, P.; Baas, F.; Strammiello, R.; van Gool, W. A.; van Swieten, J. C.; Rozemuller, A. J. Prion Protein Amyloidosis With Divergent Phenotype Associated With Two Novel Nonsense Mutations in PRNP Acta Neuropathol. 2010, 119, 189-197
15. Jayadev, S.; Nochlin, D.; Poorkaj, P.; Steinbart, E. J.; Mastrianni, J. A.; Montine, T. J.; Ghetti, B.; Schellenberg, G. D.; Bird, T. D.; Leverenz, J. B. Familial Prion Disease With Alzheimer Disease-Like Tau Pathology and Clinical Phenotype Ann. Neurol. 2011, 69, 712-720
16. Mead, S.; Gandhi, S.; Beck, J.; Caine, D.; Gajulapalli, D.; Carswell, C.; Hyare, H.; Joiner, S.; Ayling, H.; Lashley, T.; Linehan, J. M.; Al-Doujaily, H.; Sharps, B.; Revesz, T.; Sandberg, M. K.; Reilly, M. M.; Koltzenburg, M.; Forbes, A.; Rudge, P.; Brandner, S.; Warren, J. D.; Wadsworth, J. D.; Wood, N. W.; Holton, J. L.; Collinge, J. A Novel Prion Disease Associated With Diarrhea and Autonomic Neuropathy N. Engl. J. Med. 2013, 369, 1904-1914
17. Tribouillard-Tanvier, D.; Striebel, J. F.; Peterson, K. E.; Chesebro, B. Analysis of Protein Levels of 24 Cytokines in Scrapie Agent-Infected Brain and Glial Cell Cultures From Mice Differing in Prion Protein Expression Levels J. Virol. 2009, 83, 11244-11253
18. Baron, G. S.; Hughson, A. G.; Raymond, G. J.; Offerdahl, D. K.; Barton, K. A.; Raymond, L. D.; Dorward, D. W.; Caughey, B. Effect of Glycans and the Glycophosphatidylinositol Anchor on Strain Dependent Conformations of Scrapie Prion Protein: Improved Purifications and Infrared Spectra Biochemistry 2011, 50, 4479-4490
19. Sorensen, G.; Medina, S.; Parchaliuk, D.; Phillipson, C.; Robertson, C.; Booth, S. A. Comprehensive Transcriptional Profiling of Prion Infection in Mouse Models Reveals Networks of Responsive Genes BMC Genomics 2008, 9, 114
20. Skinner, P. J.; Abbassi, H.; Chesebro, B.; Race, R. E.; Reilly, C.; Haase, A. T. Gene Expression Alterations in Brains of Mice Infected With Three Strains of Scrapie BMC Genomics 2006, 7, 114
21. Booth, S.; Bowman, C.; Baumgartner, R.; Sorensen, G.; Robertson, C.; Coulthart, M.; Phillipson, C.; Somorjai, R. L. Identification of Central Nervous System Genes Involved in the Host Response to the Scrapie Agent During Preclinical and Clinical Infection J. Gen. Virol. 2004, 85, 3459-3471
22. Xiang, W.; Windl, O.; Wunsch, G.; Dugas, M.; Kohlmann, A.; Dierkes, N.; Westner, I. M.; Kretzschmar, H. A. Identification of Differentially Expressed Genes in Scrapie-Infected Mouse Brains by Using Global Gene Expression Technology J. Virol. 2004, 78, 11051-11060
23. Hwang, D.; Lee, I. Y.; Yoo, H.; Gehlenborg, N.; Cho, J. H.; Petritis, B.; Baxter, D.; Pitstick, R.; Young, R.; Spicer, D.; Price, N. D.; Hohmann, J. G.; DeArmond, S. J.; Carlson, G. A.; Hood, L. E. A Systems Approach to Prion Disease Mol. Syst. Biol. 2009, 5, 252
24. Benetti, F.; Gasperini, L.; Zampieri, M.; Legname, G. Gene Expression Profiling to Identify Druggable Targets in Prion Diseases Expert. Opin. Drug Discovery 2010, 5, 177-202
25. Xiang, W.; Windl, O.; Westner, I. M.; Neumann, M.; Zerr, I.; Lederer, R. M.; Kretzschmar, H. A. Cerebral Gene Expression Profiles in Sporadic Creutzfeldt-Jakob Disease Ann. Neurol. 2005, 58, 242-257
26. Gawinecka, J.; Dieks, J.; Asif, A. R.; Carimalo, J.; Heinemann, U.; Streich, J. H.; Dihazi, H.; Schulz-Schaeffer, W.; Zerr, I. Codon 129 Polymorphism Specific Cerebrospinal Fluid Proteome Pattern in Sporadic Creutzfeldt-Jakob Disease and the Implication of Glycolytic Enzymes in Prion-Induced Pathology J. Proteome. Res. 2010, 9, 5646-5657
27. Brown, A. R.; Webb, J.; Rebus, S.; Williams, A.; Fazakerley, J. K. Identification of Up-Regulated Genes by Array Analysis in Scrapie-Infected Mouse Brains Neuropathol. Appl. Neurobiol. 2004, 30, 555-567
28. Asuni, A. A.; Gray, B.; Bailey, J.; Skipp, P.; Perry, V. H.; OConnor, V. Analysis of the Hippocampal Proteome in ME7 Prion Disease Reveals a Predominant Astrocytic Signature and Highlights the Brain-Restricted Production of Clusterin in Chronic Neurodegeneration J. Biol. Chem. 2014, 289, 4532-4545
29. Gawinecka, J.; Nowak, M.; Carimalo, J.; Cardone, F.; Asif, A. R.; Wemheuer, W. M.; Schulz-Schaeffer, W. J.; Pocchiari, M.; Zerr, I. Subtype-Specific Synaptic Proteome Alterations in Sporadic Creutzfeldt-Jakob Disease J. Alzheimers Dis. 2013, 37, 51-61
30. Campisi, E.; Cardone, F.; Graziano, S.; Galeno, R.; Pocchiari, M. Role of Proteomics in Understanding Prion Infection Expert Rev. Proteomics 2012, 9, 649-666
31. Barr, J. B.; Watson, M.; Head, M. W.; Ironside, J. W.; Harris, N.; Hogarth, C.; Fraser, J. R.; Barron, R. Differential Protein Profiling As a Potential Multi-Marker Approach for TSE Diagnosis BMC Infect. Dis. 2009, 9, 188
32. Huzarewich, R. L.; Siemens, C. G.; Booth, S. A. Application of Omics to Prion Biomarker Discovery J. Biomed. Biotechnol. 2010, 2010, 613504
33. Rangel, A.; Race, B.; Phillips, K.; Striebel, J.; Kurtz, N.; Chesebro, B. Distinct Patterns of Spread of Prion Infection in Brains of Mice Expressing Anchorless or Anchored Forms of Prion Protein Acta Neuropathol. Commun. 2014, 2, 8
34. Moore, R. A.; Timmes, A.; Wilmarth, P. A.; Priola, S. A. Comparative Profiling of Highly Enriched 22L and Chandler Mouse Scrapie Prion Protein Preparations Proteomics 2010, 10, 2858-2869
35. Weatherly, D. B.; Atwood, J. A., III; Minning, T. A.; Cavola, C.; Tarleton, R. L.; Orlando, R. A Heuristic Method for Assigning a False-Discovery Rate for Protein Identifications From Mascot Database Search Results Mol. Cell Proteomics 2005, 4, 762-772
36. Nesvizhskii, A. I.; Keller, A.; Kolker, E.; Aebersold, R. A Statistical Model for Identifying Proteins by Tandem Mass Spectrometry Anal. Chem. 2003, 75, 4646-4658
37. Old, W. M.; Meyer-Arendt, K.; veline-Wolf, L.; Pierce, K. G.; Mendoza, A.; Sevinsky, J. R.; Resing, K. A.; Ahn, N. G. Comparison of Label-Free Methods for Quantifying Human Proteins by Shotgun Proteomics Mol. Cell Proteomics 2005, 4, 1487-1502
38. Lundgren, D. H.; Hwang, S. I.; Wu, L.; Han, D. K. Role of Spectral Counting in Quantitative Proteomics Expert Rev. Proteomics 2010, 7, 39-53
39. Benjamini, Y.; Hochberg, Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing J. R. Stat. Soc., Ser. B (Methodological) 1995, 57, 289-300
40. Liu, H.; Sadygov, R. G.; Yates, J. R., III A Model for Random Sampling and Estimation of Relative Protein Abundance in Shotgun Proteomics Anal. Chem. 2004, 76, 4193-4201
41. Mueller, L. N.; Brusniak, M. Y.; Mani, D. R.; Aebersold, R. An Assessment of Software Solutions for the Analysis of Mass Spectrometry Based Quantitative Proteomics Data J. Proteome Res. 2008, 7, 51-61
42. Sofroniew, M. V.; Vinters, H. V. Astrocytes: Biology and Pathology Acta Neuropathol. 2010, 119, 7-35
43. Levin, E. C.; Acharya, N. K.; Sedeyn, J. C.; Venkataraman, V.; DAndrea, M. R.; Wang, H. Y.; Nagele, R. G. Neuronal Expression of Vimentin in the Alzheimers Disease Brain May Be Part of a Generalized Dendritic Damage-Response Mechanism Brain Res. 2009, 1298, 194-207
44. Provansal, M.; Roche, S.; Pastore, M.; Casanova, D.; Belondrade, M.; Alais, S.; Leblanc, P.; Windl, O.; Lehmann, S. Proteomic Consequences of Expression and Pathological Conversion of the Prion Protein in Inducible Neuroblastoma N2a Cells Prion 2010, 4, 292-301
45. Pekny, M.; Wilhelmsson, U.; Bogestal, Y. R.; Pekna, M. The Role of Astrocytes and Complement System in Neural Plasticity Int. Rev. Neurobiol. 2007, 82, 95-111
46. Nezu, T.; Hosomi, N.; Aoki, S.; Deguchi, K.; Masugata, H.; Ichihara, N.; Ohyama, H.; Ohtsuki, T.; Kohno, M.; Matsumoto, M. Alpha2-Macroglobulin As a Promising Biomarker for Cerebral Small Vessel Disease in Acute Ischemic Stroke Patients J. Neurol. 2013, 260, 2642-2649
47. Van, G. D.; De, S. B.; Van, L. F.; Triau, E.; Dom, R. Alpha 2-Macroglobulin Expression in Neuritic-Type Plaques in Patients With Alzheimers Disease Neurobiol. Aging 1993, 14, 233-237
48. Wang, H.; Sama, A. E. Anti-Inflammatory Role of Fetuin-A in Injury and Infection Curr. Mol. Med. 2012, 12, 625-633
49. Riemer, C.; Gultner, S.; Heise, I.; Holtkamp, N.; Baier, M. Neuroinflammation in Prion Diseases: Concepts and Targets for Therapeutic Intervention CNS Neurol. Disord. Drug Targets 2009, 8, 329-341
50. Jahn, R.; Fasshauer, D. Molecular Machines Governing Exocytosis of Synaptic Vesicles Nature 2012, 490, 201-207
51. Ostermeier, C.; Brunger, A. T. Structural Basis of Rab Effector Specificity: Crystal Structure of the Small G Protein Rab3A Complexed With the Effector Domain of Rabphilin-3A Cell 1999, 96, 363-374
52. Norberg, E.; Orrenius, S.; Zhivotovsky, B. Mitochondrial Regulation of Cell Death: Processing of Apoptosis-Inducing Factor (AIF) Biochem. Biophys. Res. Commun. 2010, 396, 95-100
53. Jang, B.; Jin, J. K.; Jeon, Y. C.; Cho, H. J.; Ishigami, A.; Choi, K. C.; Carp, R. I.; Maruyama, N.; Kim, Y. S.; Choi, E. K. Involvement of Peptidylarginine Deiminase-Mediated Post-Translational Citrullination in Pathogenesis of Sporadic Creutzfeldt-Jakob Disease Acta Neuropathol. 2010, 119, 199-210
54. Gawinecka, J.; Cardone, F.; Asif, A. R.; De, P. A.; Wemheuer, W. M.; Schulz-Schaeffer, W. J.; Pocchiari, M.; Zerr, I. Sporadic Creutzfeldt-Jakob Disease Subtype-Specific Alterations of the Brain Proteome: Impact on Rab3a Recycling Proteomics 2012, 12, 3610-3620
55. Riemer, C.; Neidhold, S.; Burwinkel, M.; Schwarz, A.; Schultz, J.; Kratzschmar, J.; Monning, U.; Baier, M. Gene Expression Profiling of Scrapie-Infected Brain Tissue Biochem. Biophys. Res. Commun. 2004, 323, 556-564
56. Gasque, P.; Ischenko, A.; Legoedec, J.; Mauger, C.; Schouft, M. T.; Fontaine, M. Expression of the Complement Classical Pathway by Human Glioma in Culture. A Model for Complement Expression by Nerve Cells J. Biol. Chem. 1993, 268, 25068-25074
57. Fabrizi, C.; Colasanti, M.; Persichini, T.; Businaro, R.; Starace, G.; Lauro, G. M. Interferon Gamma Up-Regulates Alpha 2 Macroglobulin Expression in Human Astrocytoma Cells J. Neuroimmunol. 1994, 53, 31-37
58. Moore, R. A.; Timmes, A. G.; Wilmarth, P. A.; Safronetz, D.; Priola, S. A. Identification and Removal of Proteins That Co-Purify With Infectious Prion Protein Improves the Analysis of Its Secondary Structure Proteomics 2011, 11, 3853-3865
59. Giorgi, A.; Di, F. L.; Principe, S.; Mignogna, G.; Sennels, L.; Mancone, C.; Alonzi, T.; Sbriccoli, M.; De, P. A.; Rappsilber, J.; Cardone, F.; Pocchiari, M.; Maras, B.; Schinina, M. E. Proteomic Profiling of PrP27-30-Enriched Preparations Extracted From the Brain of Hamsters With Experimental Scrapie Proteomics 2009, 9, 3802-3814
60. Graham, J. F.; Kurian, D.; Agarwal, S.; Toovey, L.; Hunt, L.; Kirby, L.; Pinheiro, T. J.; Banner, S. J.; Gill, A. C. Na+/K+-ATPase Is Present in Scrapie-Associated Fibrils, Modulates PrP Misfolding in Vitro and Links PrP Function and Dysfunction PLoS ONE 2011, 6, e26813
61. Yerbury, J. J.; Poon, S.; Meehan, S.; Thompson, B.; Kumita, J. R.; Dobson, C. M.; Wilson, M. R. The Extracellular Chaperone Clusterin Influences Amyloid Formation and Toxicity by Interacting With Prefibrillar Structures FASEB J. 2007, 21, 2312-2322
62. Narita, M.; Holtzman, D. M.; Schwartz, A. L.; Bu, G. Alpha2-Macroglobulin Complexes With and Mediates the Endocytosis of Beta-Amyloid Peptide Via Cell Surface Low-Density Lipoprotein Receptor-Related Protein J. Neurochem. 1997, 69, 1904-1911
63. Rolyan, H.; Feike, A. C.; Upadhaya, A. R.; Waha, A.; Van, D. T.; Haass, C.; Birkenmeier, G.; Pietrzik, C. U.; Van, L. F.; Thal, D. R. Amyloid-Beta Protein Modulates the Perivascular Clearance of Neuronal Apolipoprotein E in Mouse Models of Alzheimers Disease J. Neural Transm. 2011, 118, 699-712
64. Zhang, H.; Kim, J. K.; Edwards, C. A.; Xu, Z.; Taichman, R.; Wang, C. Y. Clusterin Inhibits Apoptosis by Interacting With Activated Bax Nat. Cell Biol. 2005, 7, 909-915
65. Lashley, T.; Holton, J. L.; Verbeek, M. M.; Rostagno, A.; Bojsen-M?ller, M.; David, G.; van, H. J.; Braendgaard, H.; Plant, G.; Frangione, B.; Ghiso, J.; Revesz, T. Molecular Chaperons, Amyloid and Preamyloid Lesions in the BRI2 Gene-Related Dementias: a Morphological Study Neuropathol. Appl. Neurobiol. 2006, 32, 492-504
66. Desai, P. P.; Ikonomovic, M. D.; Abrahamson, E. E.; Hamilton, R. L.; Isanski, B. A.; Hope, C. E.; Klunk, W. E.; DeKosky, S. T.; Kamboh, M. I. Apolipoprotein D Is a Component of Compact but Not Diffuse Amyloid-Beta Plaques in Alzheimers Disease Temporal Cortex Neurobiol. Dis. 2005, 20, 574-582
67. Attems, J.; Jellinger, K.; Thal, D. R.; Van, N. W. Review: Sporadic Cerebral Amyloid Angiopathy Neuropathol. Appl. Neurobiol. 2011, 37, 75-93
68. Wong, B. S.; Brown, D. R.; Pan, T.; Whiteman, M.; Liu, T.; Bu, X.; Li, R.; Gambetti, P.; Olesik, J.; Rubenstein, R.; Sy, M. S. Oxidative Impairment in Scrapie-Infected Mice Is Associated With Brain Metals Perturbations and Altered Antioxidant Activities J. Neurochem. 2001, 79, 689-698
69. Clapham, D. E. Calcium Signaling Cell 2007, 131, 1047-1058
70. Torres, M.; Castillo, K.; Armisen, R.; Stutzin, A.; Soto, C.; Hetz, C. Prion Protein Misfolding Affects Calcium Homeostasis and Sensitizes Cells to Endoplasmic Reticulum Stress PLoS ONE 2010, 5, e15658
71. Trifilo, M. J.; Sanchez-Alavez, M.; Solforosi, L.; Bernard-Trifilo, J.; Kunz, S.; McGavern, D.; Oldstone, M. B. Scrapie-Induced Defects in Learning and Memory of Transgenic Mice Expressing Anchorless Prion Protein Are Associated With Alterations in the Gamma Aminobutyric Acid-Ergic Pathway J. Virol. 2008, 82, 9890-9899
72. Ferrer, I.; Rivera, R.; Blanco, R.; Marti, E. Expression of Proteins Linked to Exocytosis and Neurotransmission in Patients With Creutzfeldt-Jakob Disease Neurobiol. Dis. 1999, 6, 92-100
73. Jeffrey, M.; Halliday, W. G.; Bell, J.; Johnston, A. R.; MacLeod, N. K.; Ingham, C.; Sayers, A. R.; Brown, D. A.; Fraser, J. R. Synapse Loss Associated With Abnormal PrP Precedes Neuronal Degeneration in the Scrapie-Infected Murine Hippocampus Neuropathol. Appl. Neurobiol. 2000, 26, 41-54
74. Siskova, Z.; Reynolds, R. A.; OConnor, V.; Perry, V. H. Brain Region Specific Pre-Synaptic and Post-Synaptic Degeneration Are Early Components of Neuropathology in Prion Disease PLoS ONE 2013, 8, e55004
75. Siso, S.; Puig, B.; Varea, R.; Vidal, E.; Acin, C.; Prinz, M.; Montrasio, F.; Badiola, J.; Aguzzi, A.; Pumarola, M.; Ferrer, I. Abnormal Synaptic Protein Expression and Cell Death in Murine Scrapie Acta Neuropathol. 2002, 103, 615-626
76. Moreno, J. A.; Radford, H.; Peretti, D.; Steinert, J. R.; Verity, N.; Martin, M. G.; Halliday, M.; Morgan, J.; Dinsdale, D.; Ortori, C. A.; Barrett, D. A.; Tsaytler, P.; Bertolotti, A.; Willis, A. E.; Bushell, M.; Mallucci, G. R. Sustained Translational Repression by EIF2alpha-P Mediates Prion Neurodegeneration Nature 2012, 485, 507-511
77. Kristiansen, M.; Deriziotis, P.; Dimcheff, D. E.; Jackson, G. S.; Ovaa, H.; Naumann, H.; Clarke, A. R.; van Leeuwen, F. W.; Menendez-Benito, V.; Dantuma, N. P.; Portis, J. L.; Collinge, J.; Tabrizi, S. J. Disease-Associated Prion Protein Oligomers Inhibit the 26S Proteasome Mol. Cell 2007, 26, 175-188
78. Lin, Z.; Zhao, D.; Yang, L. Interaction Between Misfolded PrP and the Ubiquitin-Proteasome System in Prion-Mediated Neurodegeneration Acta Biochim. Biophys. Sin. (Shanghai) 2013, 45, 477-484
79. Choi, S. I.; Ju, W. K.; Choi, E. K.; Kim, J.; Lea, H. Z.; Carp, R. I.; Wisniewski, H. M.; Kim, Y. S. Mitochondrial Dysfunction Induced by Oxidative Stress in the Brains of Hamsters Infected With the 263 K Scrapie Agent Acta Neuropathol. 1998, 96, 279-286
80. Siskova, Z.; Mahad, D. J.; Pudney, C.; Campbell, G.; Cadogan, M.; Asuni, A.; OConnor, V.; Perry, V. H. Morphological and Functional Abnormalities in Mitochondria Associated With Synaptic Degeneration in Prion Disease Am. J. Pathol. 2010, 177, 1411-1421
81. Scorrano, L.; Ashiya, M.; Buttle, K.; Weiler, S.; Oakes, S. A.; Mannella, C. A.; Korsmeyer, S. J. A Distinct Pathway Remodels Mitochondrial Cristae and Mobilizes Cytochrome c During Apoptosis Dev. Cell 2002, 2, 55-67
82. Polster, B. M.; Fiskum, G. Mitochondrial Mechanisms of Neural Cell Apoptosis J. Neurochem. 2004, 90, 1281-1289
83. Linden, R.; Martins, V. R.; Prado, M. A.; Cammarota, M.; Izquierdo, I.; Brentani, R. R. Physiology of the Prion Protein Physiol. Rev. 2008, 88, 673-728