{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:49:05Z","timestamp":1790477345774,"version":"4.1.0"},"reference-count":166,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The prion diseases are a collection of fatal, transmissible neurodegenerative diseases that cause rapid onset dementia and ultimately death. Uniquely, the infectious agent is a misfolded form of the endogenous cellular prion protein, termed PrPSc. Despite the identity of the molecular agent remaining the same, PrPSc can cause a range of diseases with hereditary, spontaneous or iatrogenic aetiologies. However, the link between PrPSc and toxicity is complex, with subclinical cases of prion disease discovered, and prion neurodegeneration without obvious PrPSc deposition. The toxic mechanisms by which PrPSc causes the extensive neuropathology are still poorly understood, although recent advances are beginning to unravel the molecular underpinnings, including oxidative stress, disruption of proteostasis and induction of the unfolded protein response. This review will discuss the diseases caused by PrPSc toxicity, the nature of the toxicity of PrPSc, and our current understanding of the downstream toxic signaling events triggered by the presence of PrPSc.<\/jats:p>","DOI":"10.3390\/pathogens6040063","type":"journal-article","created":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T12:30:16Z","timestamp":1512131416000},"page":"63","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["What Is Our Current Understanding of PrPSc-Associated Neurotoxicity and Its Molecular Underpinnings?"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9706-5163","authenticated-orcid":false,"given":"Daniel","family":"Hughes","sequence":"first","affiliation":[{"name":"MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Halliday","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0AH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a031336","DOI":"10.1101\/cshperspect.a031336","article-title":"Toward the atomic structure of PrPSc","volume":"9","author":"Rodriguez","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fmolb.2017.00019","article-title":"Physiological functions of the cellular prion protein","volume":"4","author":"Castle","year":"2017","journal-title":"Front. Mol. Biosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0092-8674(87)90150-4","article-title":"Scrapie prion protein contains a phosphatidylinositol glycolipid","volume":"51","author":"Stahl","year":"1987","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/mrd.22057","article-title":"Developmental expression of the cellular prion protein (prp(c)) in bovine embryos","volume":"79","author":"Peralta","year":"2012","journal-title":"Mol. Reprod. Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1101\/SQB.1996.061.01.050","article-title":"Prion protein structure and scrapie replication: Theoretical, spectroscopic, and genetic investigations","volume":"61","author":"Bamborough","year":"1996","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wulf, M.A., Senatore, A., and Aguzzi, A. (2017). The biological function of the cellular prion protein: An update. BMC Biol., 15.","DOI":"10.1186\/s12915-017-0375-5"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/nn.2483","article-title":"Axonal prion protein is required for peripheral myelin maintenance","volume":"13","author":"Bremer","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/37783","article-title":"The cellular prion protein binds copper in vivo","volume":"390","author":"Brown","year":"1997","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/22241","article-title":"Prions prevent neuronal cell-line death","volume":"400","author":"Kuwahara","year":"1999","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39145","DOI":"10.1074\/jbc.C100443200","article-title":"Prion protein protects human neurons against bax-mediated apoptosis","volume":"276","author":"Bounhar","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1046\/j.1471-4159.2003.01529.x","article-title":"Tethering the n-terminus of the prion protein compromises the cellular response to oxidative stress","volume":"84","author":"Zeng","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/emboj\/21.3.202","article-title":"Post-natal knockout of prion protein alters hippocampal ca1 properties, but does not result in neurodegeneration","volume":"21","author":"Mallucci","year":"2002","journal-title":"EMBO J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1023\/A:1026315006619","article-title":"Prion protein is necessary for latent learning and long-term memory retention","volume":"17","author":"Nishida","year":"1997","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.brainres.2007.05.010","article-title":"Contributions of neuronal prion protein on sleep recovery and stress response following sleep deprivation","volume":"1158","author":"Conti","year":"2007","journal-title":"Brain Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11330","DOI":"10.1523\/JNEUROSCI.2313-05.2005","article-title":"Interaction of cellular prion and stress-inducible protein 1 promotes neuritogenesis and neuroprotection by distinct signaling pathways","volume":"25","author":"Lopes","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1096\/fj.11-185579","article-title":"Neuritogenesis: The prion protein controls beta1 integrin signaling activity","volume":"26","author":"Loubet","year":"2012","journal-title":"FASEB J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10962","DOI":"10.1073\/pnas.90.23.10962","article-title":"Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins","volume":"90","author":"Pan","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.virusres.2015.03.008","article-title":"Proteinase k and the structure of PrPSc: The good, the bad and the ugly","volume":"207","author":"Silva","year":"2015","journal-title":"Virus Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1042\/bj3180035","article-title":"Prion diseases and the \u2018protein only\u2019 hypothesis: A theoretical dynamic study","volume":"318","author":"Laurent","year":"1996","journal-title":"Biochem. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cell.2005.02.011","article-title":"In vitro generation of infectious scrapie prions","volume":"121","author":"Castilla","year":"2005","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1126\/science.3014653","article-title":"Human prion protein cdna: Molecular cloning, chromosomal mapping, and biological implications","volume":"233","author":"Liao","year":"1986","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1089\/dna.1986.5.315","article-title":"Molecular cloning of a human prion protein cdna","volume":"5","author":"Kretzschmar","year":"1986","journal-title":"DNA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.neuro.24.1.519","article-title":"Prion diseases of humans and animals: Their causes and molecular basis","volume":"24","author":"Collinge","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1126\/science.1675487","article-title":"Molecular biology of prion diseases","volume":"252","author":"Prusiner","year":"1991","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/352340a0","article-title":"Homozygous prion protein genotype predisposes to sporadic creutzfeldt-jakob disease","volume":"352","author":"Palmer","year":"1991","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3603","DOI":"10.1074\/jbc.M809254200","article-title":"Human prion protein (prp) 219k is converted to PrPSc but shows heterozygous inhibition in variant creutzfeldt-jakob disease infection","volume":"284","author":"Hizume","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"a006833","DOI":"10.1101\/cshperspect.a006833","article-title":"Prions","volume":"3","author":"Colby","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1007\/s00415-002-0896-9","article-title":"Mutations of the prion protein gene phenotypic spectrum","volume":"249","author":"Kovacs","year":"2002","journal-title":"J. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1186\/1743-422X-8-559","article-title":"An overview of human prion diseases","volume":"8","author":"Imran","year":"2011","journal-title":"Virol. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/bmb\/66.1.213","article-title":"Sporadic and familial cjd: Classification and characterisation","volume":"66","author":"Gambetti","year":"2003","journal-title":"Br. Med. Bull."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1056\/NEJM195711142572005","article-title":"Degenerative disease of the central nervous system in new guinea: The endemic occurrence of kuru in the native population","volume":"257","author":"Gajdusek","year":"1957","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1056\/NEJM198509193131207","article-title":"Clinical and pathological features and laboratory confirmation of creutzfeldt-jakob disease in a recipient of pituitary-derived human growth hormone","volume":"313","author":"Gibbs","year":"1985","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/S0140-6736(95)91827-2","article-title":"Sporadic creutzfeldt-jakob disease in a 16-year-old in the UK","volume":"346","author":"Britton","year":"1995","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/S0140-6736(95)91828-0","article-title":"Sporadic creutzfeldt-jakob disease in a 18-year-old in the UK","volume":"346","author":"Bateman","year":"1995","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/S0140-6736(96)91412-9","article-title":"A new variant of creutzfeldt-jakob disease in the uk","volume":"347","author":"Will","year":"1996","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/383685a0","article-title":"Molecular analysis of prion strain variation and the aetiology of \u2018new variant\u2019 cjd","volume":"383","author":"Collinge","year":"1996","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/38925","article-title":"The same prion strain causes vcjd and bse","volume":"389","author":"Hill","year":"1997","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1093\/oxfordjournals.aje.a009064","article-title":"Bovine spongiform encephalopathy (bse): Causes and consequences of a common source epidemic","volume":"145","author":"Nathanson","year":"1997","journal-title":"Am. J. Epidemiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"676","DOI":"10.7589\/0090-3558-36.4.676","article-title":"Epizootiology of chronic wasting disease in free-ranging cervids in colorado and wyoming","volume":"36","author":"Miller","year":"2000","journal-title":"J. Wildl. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1146\/annurev-animal-022114-111001","article-title":"Chronic wasting disease of cervids: Current knowledge and future perspectives","volume":"3","author":"Haley","year":"2015","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13567-016-0375-4","article-title":"First case of chronic wasting disease in europe in a norwegian free-ranging reindeer","volume":"47","author":"Benestad","year":"2016","journal-title":"Vet. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1242\/dmm.012146","article-title":"Selective vulnerability to neurodegenerative disease: The curious case of prion protein","volume":"7","author":"Jackson","year":"2014","journal-title":"Dis. Model. Mech."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1054\/jocn.2001.0919","article-title":"Gerstmann-straussler-scheinker syndrome, fatal familial insomnia, and kuru: A review of these less common human transmissible spongiform encephalopathies","volume":"8","author":"Collins","year":"2001","journal-title":"J. Clin. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1474-4422(03)00323-5","article-title":"Familial and sporadic fatal insomnia","volume":"2","author":"Montagna","year":"2003","journal-title":"Lancet Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/356577a0","article-title":"Normal development and behaviour of mice lacking the neuronal cell-surface prp protein","volume":"356","author":"Bueler","year":"1992","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/BF02780662","article-title":"129\/ola mice carrying a null mutation in prp that abolishes mrna production are developmentally normal","volume":"8","author":"Manson","year":"1994","journal-title":"Mol. Neurobiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1099\/vir.0.81384-0","article-title":"Functional disruption of the prion protein gene in cloned goats","volume":"87","author":"Yu","year":"2006","journal-title":"J. Gen. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/nbt1271","article-title":"Production of cattle lacking prion protein","volume":"25","author":"Richt","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"83","DOI":"10.4161\/pri.1.2.4346","article-title":"The prion protein knockout mouse: A phenotype under challenge","volume":"1","author":"Steele","year":"2007","journal-title":"Prion"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0002-9440(10)63291-9","article-title":"Prion protein accumulation and neuroprotection in hypoxic brain damage","volume":"165","author":"McLennan","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/380528a0","article-title":"Loss of cerebellar purkinje cells in aged mice homozygous for a disrupted prp gene","volume":"380","author":"Sakaguchi","year":"1996","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1006\/jmbi.1999.3108","article-title":"Ataxia in prion protein (prp)-deficient mice is associated with upregulation of the novel prp-like protein doppel","volume":"292","author":"Moore","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1023\/A:1020698305911","article-title":"Impaired motor coordination in mice lacking prion protein","volume":"18","author":"Katamine","year":"1998","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.bbrc.2004.05.115","article-title":"Doppel-induced purkinje cell death is stoichiometrically abrogated by prion protein","volume":"319","author":"Yamaguchi","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0014-5793(03)00012-7","article-title":"Prion-like protein doppel expression is not modified in scrapie-infected cells and in the brains of patients with creutzfeldt-jakob disease","volume":"536","author":"Volland","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/0092-8674(93)90360-3","article-title":"Mice devoid of prp are resistant to scrapie","volume":"73","author":"Bueler","year":"1993","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/379339a0","article-title":"Normal host prion protein necessary for scrapie-induced neurotoxicity","volume":"379","author":"Brandner","year":"1996","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1126\/science.1090187","article-title":"Depleting neuronal prp in prion infection prevents disease and reverses spongiosis","volume":"302","author":"Mallucci","year":"2003","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1126\/science.1110837","article-title":"Anchorless prion protein results in infectious amyloid disease without clinical scrapie","volume":"308","author":"Chesebro","year":"2005","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/bmb\/66.1.161","article-title":"Subclinical prion infection in humans and animals","volume":"66","author":"Hill","year":"2003","journal-title":"Br. Med. Bull."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1126\/science.275.5298.402","article-title":"Transmission of the bse agent to mice in the absence of detectable abnormal prion protein","volume":"275","author":"Lasmezas","year":"1997","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1126\/science.277.5322.94","article-title":"Evolution of a strain of cjd that induces bse-like plaques","volume":"277","author":"Manuelidis","year":"1997","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/ana.410420203","article-title":"Familial spongiform encephalopathy associated with a novel prion protein gene mutation","volume":"42","author":"Nitrini","year":"1997","journal-title":"Ann. Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1001\/archneur.57.7.1058","article-title":"Novel prion protein gene mutation in an octogenarian with creutzfeldt-jakob disease","volume":"57","author":"Collins","year":"2000","journal-title":"Arch. Neurol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1007\/s00401-004-0913-4","article-title":"Loss of glycosylation associated with the t183a mutation in human prion disease","volume":"108","author":"Lorenz","year":"2004","journal-title":"Acta Neuropathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1126\/science.279.5352.827","article-title":"A transmembrane form of the prion protein in neurodegenerative disease","volume":"279","author":"Hegde","year":"1998","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"10248","DOI":"10.1073\/pnas.97.18.10248","article-title":"Species-barrier-independent prion replication in apparently resistant species","volume":"97","author":"Hill","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"10106","DOI":"10.1128\/JVI.75.21.10106-10112.2001","article-title":"Long-term subclinical carrier state precedes scrapie replication and adaptation in a resistant species: Analogies to bovine spongiform encephalopathy and variant creutzfeldt-jakob disease in humans","volume":"75","author":"Race","year":"2001","journal-title":"J. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.tim.2003.10.007","article-title":"Subclinical prion infection","volume":"11","author":"Hill","year":"2003","journal-title":"Trends Microbiol."},{"key":"ref_70","first-page":"39","article-title":"Purification of scrapie agents: How far have we come?","volume":"172","author":"Bolton","year":"1991","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/nature03989","article-title":"The most infectious prion protein particles","volume":"437","author":"Silveira","year":"2005","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"12868","DOI":"10.1021\/bi025958g","article-title":"Protease-sensitive scrapie prion protein in aggregates of heterogeneous sizes","volume":"41","author":"Tzaban","year":"2002","journal-title":"Biochemistry"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"15710","DOI":"10.1021\/bi0615442","article-title":"Isolation and characterization of a proteinase k-sensitive PrPSc fraction","volume":"45","author":"Pastrana","year":"2006","journal-title":"Biochemistry"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Sajnani, G., Silva, C.J., Ramos, A., Pastrana, M.A., Onisko, B.C., Erickson, M.L., Antaki, E.M., Dynin, I., Vazquez-Fernandez, E., and Sigurdson, C.J. (2012). Pk-sensitive prp is infectious and shares basic structural features with pk-resistant prp. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002547"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/BF03403528","article-title":"High prion and PrPSc levels but delayed onset of disease in scrapie-inoculated mice heterozygous for a disrupted prp gene","volume":"1","author":"Bueler","year":"1994","journal-title":"Mol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1111\/j.1471-4159.2008.05306.x","article-title":"Non-infectious aggregates of the prion protein react with several PrPSc-directed antibodies","volume":"105","author":"Biasini","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1128\/jvi.70.3.1714-1722.1996","article-title":"Disruption of prion rods generates 10-nm spherical particles having high alpha-helical content and lacking scrapie infectivity","volume":"70","author":"Riesner","year":"1996","journal-title":"J. Virol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.bbadis.2006.12.006","article-title":"The prion strain phenomenon: Molecular basis and unprecedented features","volume":"1772","author":"Morales","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/2654","article-title":"Eight prion strains have prp(sc) molecules with different conformations","volume":"4","author":"Safar","year":"1998","journal-title":"Nat. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1073\/pnas.83.8.2310","article-title":"Separation and properties of cellular and scrapie prion proteins","volume":"83","author":"Meyer","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/36337","article-title":"Prion (PrPSc)-specific epitope defined by a monoclonal antibody","volume":"390","author":"Korth","year":"1997","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/j.cell.2012.02.022","article-title":"The amyloid state of proteins in human diseases","volume":"148","author":"Eisenberg","year":"2012","journal-title":"Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nature09768","article-title":"Prion propagation and toxicity in vivo occur in two distinct mechanistic phases","volume":"470","author":"Sandberg","year":"2011","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.1021\/acs.biochem.5b00605","article-title":"Molecular mechanism of the misfolding and oligomerization of the prion protein: Current understanding and its implications","volume":"54","author":"Singh","year":"2015","journal-title":"Biochemistry"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.bbrc.2004.12.172","article-title":"An unusual soluble beta-turn-rich conformation of prion is involved in fibril formation and toxic to neuronal cells","volume":"328","author":"Kazlauskaite","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"13828","DOI":"10.1074\/jbc.M511174200","article-title":"Amyloid fibrils of mammalian prion protein are highly toxic to cultured cells and primary neurons","volume":"281","author":"Novitskaya","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Simoneau, S., Rezaei, H., Sales, N., Kaiser-Schulz, G., Lefebvre-Roque, M., Vidal, C., Fournier, J.G., Comte, J., Wopfner, F., and Grosclaude, J. (2007). In vitro and in vivo neurotoxicity of prion protein oligomers. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030125"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/jnc.13772","article-title":"Pathogenic mechanisms of prion protein, amyloid-beta and alpha-synuclein misfolding: The prion concept and neurotoxicity of protein oligomers","volume":"139","author":"Ugalde","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1038\/emboj.2011.86","article-title":"The cellular prion protein mediates neurotoxic signalling of beta-sheet-rich conformers independent of prion replication","volume":"30","author":"Resenberger","year":"2011","journal-title":"EMBO J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/BF00688178","article-title":"Neuronal autophagy in experimental creutzfeldt-jakob\u2019s disease","volume":"78","author":"Boellaard","year":"1989","journal-title":"Acta Neuropathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/BF00294449","article-title":"Neuronal autophagy in experimental scrapie","volume":"82","author":"Boellaard","year":"1991","journal-title":"Acta Neuropathol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/BF00308472","article-title":"Neuronal autophagic vacuoles in experimental scrapie and creutzfeldt-jakob disease","volume":"83","author":"Liberski","year":"1992","journal-title":"Acta Neuropathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1016\/j.biocel.2004.04.014","article-title":"Autophagy is a part of ultrastructural synaptic pathology in creutzfeldt-jakob disease: A brain biopsy study","volume":"36","author":"Sikorska","year":"2004","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.4161\/auto.21482","article-title":"Activation of the macroautophagic system in scrapie-infected experimental animals and human genetic prion diseases","volume":"8","author":"Xu","year":"2012","journal-title":"Autophagy"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1471-4159.2009.05906.x","article-title":"Lithium induces clearance of protease resistant prion protein in prion-infected cells by induction of autophagy","volume":"109","author":"Heiseke","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"7044","DOI":"10.1073\/pnas.1303510110","article-title":"Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents","volume":"110","author":"Karapetyan","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.4161\/auto.25381","article-title":"Fk506 reduces abnormal prion protein through the activation of autolysosomal degradation and prolongs survival in prion-infected mice","volume":"9","author":"Nakagaki","year":"2013","journal-title":"Autophagy"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"12396","DOI":"10.1523\/JNEUROSCI.6189-11.2012","article-title":"Rapamycin delays disease onset and prevents prp plaque deposition in a mouse model of gerstmann-straussler-scheinker disease","volume":"32","author":"Cortes","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1750-3639.1995.tb00597.x","article-title":"Neuronal cell death in scrapie-infected mice is due to apoptosis","volume":"5","author":"Giese","year":"1995","journal-title":"Brain Pathol."},{"key":"ref_101","first-page":"283","article-title":"Neuronal loss and apoptosis in experimental creutzfeldt-jakob disease in mice","volume":"37","author":"Buczynski","year":"1999","journal-title":"Folia Neuropathol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1097\/00005072-199904000-00002","article-title":"Neuronal apoptosis in creutzfeldt-jakob disease","volume":"58","author":"Gray","year":"1999","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.brainres.2010.01.089","article-title":"Distribution of apoptosis-related proteins in sporadic creutzfeldt-jakob disease","volume":"1323","author":"Kovacs","year":"2010","journal-title":"Brain Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/NEN.0b013e3182084a8c","article-title":"Optical imaging detects apoptosis in the brain and peripheral organs of prion-infected mice","volume":"70","author":"Drew","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.nbd.2006.05.013","article-title":"Bax deletion does not protect neurons from bse-induced death","volume":"23","author":"Coulpier","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"13022","DOI":"10.1523\/JNEUROSCI.3290-07.2007","article-title":"Diminishing apoptosis by deletion of bax or overexpression of bcl-2 does not protect against infectious prion toxicity in vivo","volume":"27","author":"Steele","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"243","DOI":"10.4161\/pri.1.4.5551","article-title":"Prion pathogenesis is independent of caspase-12","volume":"1","author":"Steele","year":"2007","journal-title":"Prion"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1152\/physrev.00027.2001","article-title":"The ubiquitin-proteasome proteolytic pathway: Destruction for the sake of construction","volume":"82","author":"Glickman","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s00401-015-1508-y","article-title":"Prion-mediated neurodegeneration is associated with early impairment of the ubiquitin-proteasome system","volume":"131","author":"McKinnon","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"32","DOI":"10.4161\/pri.6.1.18272","article-title":"Misfolded prp and a novel mechanism of proteasome inhibition","volume":"6","author":"Andre","year":"2012","journal-title":"Prion"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1038\/emboj.2011.224","article-title":"Misfolded prp impairs the ups by interaction with the 20s proteasome and inhibition of substrate entry","volume":"30","author":"Deriziotis","year":"2011","journal-title":"EMBO J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.molcel.2007.04.001","article-title":"Disease-associated prion protein oligomers inhibit the 26s proteasome","volume":"26","author":"Kristiansen","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1093\/abbs\/gmt020","article-title":"Interaction between misfolded prp and the ubiquitin-proteasome system in prion-mediated neurodegeneration","volume":"45","author":"Lin","year":"2013","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1099\/vir.0.010082-0","article-title":"Proteasome inhibitors promote the sequestration of PrPSc into aggresomes within the cytosol of prion-infected cad neuronal cells","volume":"90","author":"Dron","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"4504","DOI":"10.1038\/srep04504","article-title":"Increased expression of p62\/sqstm1 in prion diseases and its association with pathogenic prion protein","volume":"4","author":"Homma","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"5435","DOI":"10.1093\/emboj\/cdg537","article-title":"Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein","volume":"22","author":"Hetz","year":"2003","journal-title":"EMBO J."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.virusres.2014.12.018","article-title":"Er stress signaling and neurodegeneration: At the intersection between alzheimer's disease and prion-related disorders","volume":"207","author":"Torres","year":"2015","journal-title":"Virus Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"19862","DOI":"10.1074\/jbc.R114.568477","article-title":"Prions: Generation and spread versus neurotoxicity","volume":"289","author":"Halliday","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e1672","DOI":"10.1038\/cddis.2015.49","article-title":"Partial restoration of protein synthesis rates by the small molecule isrib prevents neurodegeneration without pancreatic toxicity","volume":"6","author":"Halliday","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1093\/brain\/awx074","article-title":"Repurposed drugs targeting eif2alpha-p-mediated translational repression prevent neurodegeneration in mice","volume":"140","author":"Halliday","year":"2017","journal-title":"Brain"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"206ra138","DOI":"10.1126\/scitranslmed.3006767","article-title":"Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice","volume":"5","author":"Moreno","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nature11058","article-title":"Sustained translational repression by eif2alpha-p mediates prion neurodegeneration","volume":"485","author":"Moreno","year":"2012","journal-title":"Nature"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nrm3270","article-title":"The unfolded protein response: Controlling cell fate decisions under er stress and beyond","volume":"13","author":"Hetz","year":"2012","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1385\/MB:34:2:279","article-title":"The unfolded protein response","volume":"34","author":"Schroder","year":"2006","journal-title":"Mol. Biotechnol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1146\/annurev.biochem.73.011303.074134","article-title":"The mammalian unfolded protein response","volume":"74","author":"Schroder","year":"2005","journal-title":"Annu. Rev. Biochem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1126\/science.1209038","article-title":"The unfolded protein response: From stress pathway to homeostatic regulation","volume":"334","author":"Walter","year":"2011","journal-title":"Science"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1083\/jcb.153.5.1011","article-title":"Feedback inhibition of the unfolded protein response by gadd34-mediated dephosphorylation of eif2alpha","volume":"153","author":"Novoa","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"7193","DOI":"10.1021\/jm300713s","article-title":"Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1h-indol-5-yl)-7h-p yrrolo[2,3-d]pyrimidin-4-amine (gsk2606414), a potent and selective first-in-class inhibitor of protein kinase r (pkr)-like endoplasmic reticulum kinase (perk)","volume":"55","author":"Axten","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1126\/science.aaa6986","article-title":"Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound","volume":"348","author":"Sekine","year":"2015","journal-title":"Science"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/mmi.12930","article-title":"Oxidative stress conditions increase the frequency of de novo formation of the yeast [psi+] prion","volume":"96","author":"Doronina","year":"2015","journal-title":"Mol. Microbiol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/j.freeradbiomed.2009.02.013","article-title":"Uv-light-induced conversion and aggregation of prion proteins","volume":"46","author":"Redecke","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s12031-013-0008-6","article-title":"Cellular prion protein (PrPC) of the neuron cell transformed to a pk-resistant protein under oxidative stress, comprising main mitochondrial damage in prion diseases","volume":"51","author":"Yuan","year":"2013","journal-title":"J. Mol. Neurosci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1042\/bj3340423","article-title":"Prion protein expression and superoxide dismutase activity","volume":"334","author":"Brown","year":"1998","journal-title":"Biochem. J."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bbrc.2004.12.132","article-title":"Prp cooperates with sti1 to regulate sod activity in prp-deficient neuronal cell line","volume":"328","author":"Sakudo","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0304-3940(00)01277-5","article-title":"Induction of heme oxygenase-1 in the brains of scrapie-infected mice","volume":"289","author":"Choi","year":"2000","journal-title":"Neurosci. Lett."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s004010050895","article-title":"Mitochondrial dysfunction induced by oxidative stress in the brains of hamsters infected with the 263 k scrapie agent","volume":"96","author":"Choi","year":"1998","journal-title":"Acta Neuropathol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1080\/10715769900300541","article-title":"Alteration of free radical metabolism in the brain of mice infected with scrapie agent","volume":"30","author":"Lee","year":"1999","journal-title":"Free Radic. Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1046\/j.1365-2990.2000.026002143.x","article-title":"Dendritic and synaptic alterations of hippocampal pyramidal neurones in scrapie-infected mice","volume":"26","author":"Belichenko","year":"2000","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1046\/j.1365-2990.2000.00216.x","article-title":"Synapse loss associated with abnormal prp precedes neuronal degeneration in the scrapie-infected murine hippocampus","volume":"26","author":"Jeffrey","year":"2000","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1097\/00001756-200101220-00043","article-title":"Early loss of dendritic spines in murine scrapie revealed by confocal analysis","volume":"12","author":"Brown","year":"2001","journal-title":"Neuroreport"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.nbd.2009.04.001","article-title":"Selective presynaptic degeneration in the synaptopathy associated with me7-induced hippocampal pathology","volume":"35","author":"Gray","year":"2009","journal-title":"Neurobiol. Dis."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.neuron.2007.01.005","article-title":"Targeting cellular prion protein reverses early cognitive deficits and neurophysiological dysfunction in prion-infected mice","volume":"53","author":"Mallucci","year":"2007","journal-title":"Neuron"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1046\/j.1460-9568.2003.02662.x","article-title":"Synaptic changes characterize early behavioural signs in the me7 model of murine prion disease","volume":"17","author":"Cunningham","year":"2003","journal-title":"Eur. J. Neurosci."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.nbd.2005.12.002","article-title":"An integrated, temporal study of the behavioural, electrophysiological and neuropathological consequences of murine prion disease","volume":"22","author":"Chiti","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1097\/00001756-199301000-00017","article-title":"Synaptic degeneration is the primary neuropathological feature in prion disease: A preliminary study","volume":"4","author":"Clinton","year":"1993","journal-title":"Neuroreport"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.mcn.2003.09.019","article-title":"Astrocytic regulation of nmda receptor subunit composition modulates the toxicity of prion peptide prp106-126","volume":"25","author":"Sassoon","year":"2004","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.nbd.2008.06.007","article-title":"Hippocampal bursts caused by changes in nmda receptor-dependent excitation in a mouse model of variant cjd","volume":"32","author":"Ratte","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1083\/jcb.200711002","article-title":"Prion protein attenuates excitotoxicity by inhibiting nmda receptors","volume":"181","author":"Khosravani","year":"2008","journal-title":"J. Cell Biol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/418291a","article-title":"Neurodegenerative disease: Amyloid pores from pathogenic mutations","volume":"418","author":"Lashuel","year":"2002","journal-title":"Nature"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"10427","DOI":"10.1073\/pnas.0502066102","article-title":"Amyloid ion channels: A common structural link for protein-misfolding disease","volume":"102","author":"Quist","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"10905","DOI":"10.1128\/JVI.76.21.10905-10913.2002","article-title":"Microglia from creutzfeldt-jakob disease-infected brains are infectious and show specific mrna activation profiles","volume":"76","author":"Baker","year":"2002","journal-title":"J. Virol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/j.1750-3639.1998.tb00167.x","article-title":"Role of microglia in neuronal cell death in prion disease","volume":"8","author":"Giese","year":"1998","journal-title":"Brain Pathol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/380345a0","article-title":"Role of microglia and host prion protein in neurotoxicity of a prion protein fragment","volume":"380","author":"Brown","year":"1996","journal-title":"Nature"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Grizenkova, J., Akhtar, S., Brandner, S., Collinge, J., and Lloyd, S.E. (2014). Microglial cx3cr1 knockout reduces prion disease incubation time in mice. BMC Neurosci., 15.","DOI":"10.1186\/1471-2202-15-44"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1084\/jem.20151000","article-title":"A neuroprotective role for microglia in prion diseases","volume":"213","author":"Zhu","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1002\/glia.21070","article-title":"Microglia in the degenerating brain are capable of phagocytosis of beads and of apoptotic cells, but do not efficiently remove PrPSc, even upon lps stimulation","volume":"58","author":"Hughes","year":"2010","journal-title":"Glia"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1172\/JCI72241","article-title":"Prion disease tempo determined by host-dependent substrate reduction","volume":"124","author":"Mays","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1093\/abbs\/gmt037","article-title":"Prion protein oligomer and its neurotoxicity","volume":"45","author":"Huang","year":"2013","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"826","DOI":"10.2174\/156652409789105543","article-title":"Prion protein misfolding","volume":"9","author":"Kupfer","year":"2009","journal-title":"Curr. Mol. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"138","DOI":"10.4103\/0972-2327.144284","article-title":"Toxic species in amyloid disorders: Oligomers or mature fibrils","volume":"18","author":"Verma","year":"2015","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1099\/vir.0.80947-0","article-title":"Prion clearance in bigenic mice","volume":"86","author":"Safar","year":"2005","journal-title":"J. Gen. Virol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"10238","DOI":"10.1073\/pnas.0802759105","article-title":"Single treatment with rnai against prion protein rescues early neuronal dysfunction and prolongs survival in mice with prion disease","volume":"105","author":"White","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"12889","DOI":"10.1128\/JVI.01563-07","article-title":"Orally administered amyloidophilic compound is effective in prolonging the incubation periods of animals cerebrally infected with prion diseases in a prion strain-dependent manner","volume":"81","author":"Kawasaki","year":"2007","journal-title":"J. Virol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1093\/brain\/awl150","article-title":"A systematic review of prion therapeutics in experimental models","volume":"129","author":"Trevitt","year":"2006","journal-title":"Brain"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2174\/1871526510909010081","article-title":"Recent advances in prion chemotherapeutics","volume":"9","author":"Sim","year":"2009","journal-title":"Infect. Disord. Drug Targets"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"14529","DOI":"10.1073\/pnas.96.25.14529","article-title":"Elimination of prions by branched polyamines and implications for therapeutics","volume":"96","author":"Supattapone","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/6\/4\/63\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:52:09Z","timestamp":1760208729000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/6\/4\/63"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,1]]},"references-count":166,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["pathogens6040063"],"URL":"https:\/\/doi.org\/10.3390\/pathogens6040063","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,1]]}}}