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Title: | Regional and subtype-dependent miRNA signatures in sporadic Creutzfeldt-Jakob disease are accompanied by alterations in miRNA silencing machinery and biogenesis |
Author: | Llorens Torres, Franc Thüne, Katrin Martí Puig, Eulàlia Kanata, Eirini Dafou, Dimitra Vivancos, Ana Shomroni, Orr Zafar, Saima Schmitz, Matthias Michel, Uwe Fernández Borges, Natalia Andréoletti, Olivier Río Fernández, José Antonio del Díez, Juana Fischer, Andre Bonn, Stefan Sklaviadis, Theodoros Torres, Juan Maria Ferrer, Isidro (Ferrer Abizanda) Zerr, Inga Diaz-Lucena, Daniela Martí Puig, Eulàlia |
Keywords: | Malaltia d'Alzheimer Micro RNAs Alzheimer's disease MicroRNAs |
Issue Date: | 22-Jan-2018 |
Publisher: | Public Library of Science (PLoS) |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1371/journal.ppat.1006802 |
It is part of: | PLoS Pathogens, 2018, vol. 14, num. 1, p. e1006802 |
URI: | http://hdl.handle.net/2445/124147 |
Related resource: | https://doi.org/10.1371/journal.ppat.1006802 |
ISSN: | 1553-7366 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC)) Articles publicats en revistes (Biomedicina) |
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