{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:46:55Z","timestamp":1792036015806,"version":"4.4.0"},"reference-count":70,"publisher":"National Academy of Sciences","issue":"39","license":[{"start":{"date-parts":[[2019,9,6]],"date-time":"2019-09-06T00:00:00Z","timestamp":1567728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,9,24]]},"abstract":"<jats:p>\n                    Prion diseases are fatal neurodegenerative disorders caused by misfolding of the normal prion protein into an infectious cellular pathogen. Clinically characterized by rapidly progressive dementia and accounting for 85% of human prion disease cases, sporadic Creutzfeldt\u2013Jakob disease (sCJD) is the prevalent human prion disease. Although sCJD neuropathological hallmarks are well-known, associated molecular alterations are elusive due to rapid progression and absence of preclinical stages. To investigate transcriptome alterations during disease progression, we utilized tg340-\n                    <jats:italic>PRNP<\/jats:italic>\n                    129MM mice infected with postmortem material from sCJD patients of the most susceptible genotype (MM1 subtype), a sCJD model that faithfully recapitulates the molecular and pathological alterations of the human disease. Here we report that transcriptomic analyses from brain cortex in the context of disease progression, reveal epitranscriptomic alterations (specifically altered RNA edited pathway profiles, eg., ER stress, lysosome) that are characteristic and possibly protective mainly for preclinical and clinical disease stages. Our results implicate regulatory epitranscriptomic mechanisms in prion disease neuropathogenesis, whereby RNA-editing targets in a humanized sCJD mouse model were confirmed in pathological human autopsy material.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1803521116","type":"journal-article","created":{"date-parts":[[2019,9,6]],"date-time":"2019-09-06T20:45:27Z","timestamp":1567802727000},"page":"19727-19735","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":34,"title":["RNA editing alterations define manifestation of prion diseases"],"prefix":"10.1073","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7363-9380","authenticated-orcid":false,"given":"Eirini","family":"Kanata","sequence":"first","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franc","family":"Llorens","sequence":"additional","affiliation":[{"name":"Network Center for Biomedical Research of Neurodegenerative Diseases, Institute Carlos III, Ministry of Health, 0890X L\u2019Hospitalet de Llobregat, Spain;"},{"name":"Bellvitge Biomedical Research Institute, 08908 L\u2019Hospitalet de Llobregat, Spain;"},{"name":"Department of Neurology, University Medical School, 37075 G\u00f6ttingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Dafou","sequence":"additional","affiliation":[{"name":"Department of Genetics, Development, and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Dimitriadis","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Department of Pharmacy, 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Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Capece","sequence":"additional","affiliation":[{"name":"Microarray and Deep-Sequencing Core Facility, Institute Developmental Biochemistry, University Medical Center, 37075 G\u00f6ttingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orr","family":"Shormoni","sequence":"additional","affiliation":[{"name":"Microarray and Deep-Sequencing Core Facility, Institute Developmental Biochemistry, University Medical Center, 37075 G\u00f6ttingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Andr\u00e9oletti","sequence":"additional","affiliation":[{"name":"Interactions H\u00f4tes Agents Pathogen\u00e8s, Institut National de la Recherche Agronomique, Ecole Nationale V\u00e9t\u00e9rinaire, UMR 1225, 31300 Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4366-5662","authenticated-orcid":false,"given":"Stefan","family":"Bonn","sequence":"additional","affiliation":[{"name":"Microarray and Deep-Sequencing Core Facility, Institute Developmental Biochemistry, University Medical Center, 37075 G\u00f6ttingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0443-9232","authenticated-orcid":false,"given":"Juan Mar\u00eda","family":"Torres","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Sanidad Animal, 28130 Madrid, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"Isidre","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Network Center for Biomedical Research of Neurodegenerative Diseases, Institute Carlos III, Ministry of Health, 0890X L\u2019Hospitalet de Llobregat, Spain;"},{"name":"Bellvitge Biomedical Research Institute, 08908 L\u2019Hospitalet de Llobregat, Spain;"},{"name":"Department of Pathology and Experimental Therapeutics, University of Barcelona, 08007 L\u2019Hospitalet de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6722-2463","authenticated-orcid":false,"given":"Inga","family":"Zerr","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical School, 37075 G\u00f6ttingen, Germany;"},{"name":"Translational Studies and Biomarkers, German Center for Neurodegenerative Diseases, 37075 G\u00f6ttingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4170-0612","authenticated-orcid":false,"given":"Theodoros","family":"Sklaviadis","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Department of Pharmacy, School of 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