Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/124147
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, Eulàlia
Kanata, Eirini
Dafou, Dimitra
Vivancos, Ana
Shomroni, Orr
Zafar, Saima
Schmitz, Matthias
Michel, Uwe
Fernández Borges, Natalia
Andréoletti, Olivier
Río, José Antonio del
Díez, Juana
Fischer, Andre
Bonn, Stefan
Sklaviadis, Theodoros
Torres, Juan Maria
Ferrer, Isidro (Ferrer Abizanda)
Zerr, Inga
Díaz 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
Related resource: https://doi.org/10.1371/journal.ppat.1006802
URI: http://hdl.handle.net/2445/124147
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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