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Regional and subtype-dependent miRNA signatures in sporadic Creutzfeldt-Jakob disease are accompanied by alterations in miRNA silencing machinery and biogenesis.
Llorens, Franc; Thüne, Katrin; Martí, Eulàlia; Kanata, Eirini; Dafou, Dimitra; Díaz-Lucena, Daniela; Vivancos, Ana; Shomroni, Orr; Zafar, Saima; Schmitz, Matthias; Michel, Uwe; Fernández-Borges, Natalia; Andréoletti, Olivier; Del Río, José Antonio; Díez, Juana; Fischer, Andre; Bonn, Stefan; Sklaviadis, Theodoros; Torres, Juan Maria; Ferrer, Isidre; Zerr, Inga.
Afiliação
  • Llorens F; Department of Neurology, University Medical School, Göttingen, Germany.
  • Thüne K; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain.
  • Martí E; Department of Neurology, University Medical School, Göttingen, Germany.
  • Kanata E; German Center for Neurodegenerative Diseases (DZNE), Translational Studies and Biomarkers, Göttingen, Germany.
  • Dafou D; Centre for Genomic Regulation, Barcelona, Spain.
  • Díaz-Lucena D; Prion Diseases Research Group, School of Health Sciences, Department Of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece.
  • Vivancos A; Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
  • Shomroni O; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain.
  • Zafar S; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
  • Schmitz M; German Center for Neurodegenerative Diseases (DZNE), Computational Systems Biology, Göttingen, Germany.
  • Michel U; Department of Neurology, University Medical School, Göttingen, Germany.
  • Fernández-Borges N; German Center for Neurodegenerative Diseases (DZNE), Translational Studies and Biomarkers, Göttingen, Germany.
  • Andréoletti O; Department of Neurology, University Medical School, Göttingen, Germany.
  • Del Río JA; German Center for Neurodegenerative Diseases (DZNE), Translational Studies and Biomarkers, Göttingen, Germany.
  • Díez J; Department of Neurology, University Medical School, Göttingen, Germany.
  • Fischer A; Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.
  • Bonn S; Institut National de la Recherche Agronomique/Ecole Nationale Vétérinaire, Toulouse, France.
  • Sklaviadis T; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain.
  • Torres JM; Molecular and Cellular Neurobiotechnology, Catalonian Institute for Bioengineering (IBEC), Parc Científic de Barcelona, Barcelona, Spain.
  • Ferrer I; Department of Cell Biology, University of Barcelona, Barcelona, Spain.
  • Zerr I; Molecular Virology group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
PLoS Pathog ; 14(1): e1006802, 2018 01.
Article em En | MEDLINE | ID: mdl-29357384
ABSTRACT
Increasing evidence indicates that microRNAs (miRNAs) are contributing factors to neurodegeneration. Alterations in miRNA signatures have been reported in several neurodegenerative dementias, but data in prion diseases are restricted to ex vivo and animal models. The present study identified significant miRNA expression pattern alterations in the frontal cortex and cerebellum of sporadic Creutzfeldt-Jakob disease (sCJD) patients. These changes display a highly regional and disease subtype-dependent regulation that correlates with brain pathology. We demonstrate that selected miRNAs are enriched in sCJD isolated Argonaute(Ago)-binding complexes in disease, indicating their incorporation into RNA-induced silencing complexes, and further suggesting their contribution to disease-associated gene expression changes. Alterations in the miRNA-mRNA regulatory machinery and perturbed levels of miRNA biogenesis key components in sCJD brain samples reported here further implicate miRNAs in sCJD gene expression (de)regulation. We also show that a subset of sCJD-altered miRNAs are commonly changed in Alzheimer's disease, dementia with Lewy bodies and fatal familial insomnia, suggesting potential common mechanisms underlying these neurodegenerative processes. Additionally, we report no correlation between brain and cerebrospinal fluid (CSF) miRNA-profiles in sCJD, indicating that CSF-miRNA profiles do not faithfully mirror miRNA alterations detected in brain tissue of human prion diseases. Finally, utilizing a sCJD MM1 mouse model, we analyzed the miRNA deregulation patterns observed in sCJD in a temporal manner. While fourteen sCJD-related miRNAs were validated at clinical stages, only two of those were changed at early symptomatic phase, suggesting that the miRNAs altered in sCJD may contribute to later pathogenic processes. Altogether, the present work identifies alterations in the miRNA network, biogenesis and miRNA-mRNA silencing machinery in sCJD, whereby contributions to disease mechanisms deserve further investigation.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome de Creutzfeldt-Jakob / MicroRNAs / Interferência de RNA / Transcriptoma Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS Pathog Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome de Creutzfeldt-Jakob / MicroRNAs / Interferência de RNA / Transcriptoma Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS Pathog Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Alemanha