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RNA editing alterations define manifestation of prion diseases
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–Jakob disease (sCJD) is the p...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765247/ https://www.ncbi.nlm.nih.gov/pubmed/31492812 http://dx.doi.org/10.1073/pnas.1803521116 |
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author | Kanata, Eirini Llorens, Franc Dafou, Dimitra Dimitriadis, Athanasios Thüne, Katrin Xanthopoulos, Konstantinos Bekas, Nikolaos Espinosa, Juan Carlos Schmitz, Matthias Marín-Moreno, Alba Capece, Vincenzo Shormoni, Orr Andréoletti, Olivier Bonn, Stefan Torres, Juan María Ferrer, Isidre Zerr, Inga Sklaviadis, Theodoros |
author_facet | Kanata, Eirini Llorens, Franc Dafou, Dimitra Dimitriadis, Athanasios Thüne, Katrin Xanthopoulos, Konstantinos Bekas, Nikolaos Espinosa, Juan Carlos Schmitz, Matthias Marín-Moreno, Alba Capece, Vincenzo Shormoni, Orr Andréoletti, Olivier Bonn, Stefan Torres, Juan María Ferrer, Isidre Zerr, Inga Sklaviadis, Theodoros |
author_sort | Kanata, Eirini |
collection | PubMed |
description | 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–Jakob 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-PRNP129MM 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. |
format | Online Article Text |
id | pubmed-6765247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-67652472019-10-02 RNA editing alterations define manifestation of prion diseases Kanata, Eirini Llorens, Franc Dafou, Dimitra Dimitriadis, Athanasios Thüne, Katrin Xanthopoulos, Konstantinos Bekas, Nikolaos Espinosa, Juan Carlos Schmitz, Matthias Marín-Moreno, Alba Capece, Vincenzo Shormoni, Orr Andréoletti, Olivier Bonn, Stefan Torres, Juan María Ferrer, Isidre Zerr, Inga Sklaviadis, Theodoros Proc Natl Acad Sci U S A PNAS Plus 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–Jakob 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-PRNP129MM 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. National Academy of Sciences 2019-09-24 2019-09-06 /pmc/articles/PMC6765247/ /pubmed/31492812 http://dx.doi.org/10.1073/pnas.1803521116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | PNAS Plus Kanata, Eirini Llorens, Franc Dafou, Dimitra Dimitriadis, Athanasios Thüne, Katrin Xanthopoulos, Konstantinos Bekas, Nikolaos Espinosa, Juan Carlos Schmitz, Matthias Marín-Moreno, Alba Capece, Vincenzo Shormoni, Orr Andréoletti, Olivier Bonn, Stefan Torres, Juan María Ferrer, Isidre Zerr, Inga Sklaviadis, Theodoros RNA editing alterations define manifestation of prion diseases |
title | RNA editing alterations define manifestation of prion diseases |
title_full | RNA editing alterations define manifestation of prion diseases |
title_fullStr | RNA editing alterations define manifestation of prion diseases |
title_full_unstemmed | RNA editing alterations define manifestation of prion diseases |
title_short | RNA editing alterations define manifestation of prion diseases |
title_sort | rna editing alterations define manifestation of prion diseases |
topic | PNAS Plus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765247/ https://www.ncbi.nlm.nih.gov/pubmed/31492812 http://dx.doi.org/10.1073/pnas.1803521116 |
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