Regional and subtype-dependent miRNA signatures in sporadic Creutzfeldt-Jakob disease are accompanied by alterations in miRNA silencing machinery and biogenesis.

Llorens, Franc; Schmitz, Matthias; Andréoletti, Olivier; Vivancos, Ana; Martí, Eulàlia; Bonn, Stefan; Sklaviadis, Theodoros; Dafou, Dimitra; Ferrer, Isidre; Fernández-Borges, Natalia; Díaz-Lucena, Daniela; Michel, Uwe; Zerr, Inga; Fischer, Andre; Torres, Juan Maria; Zafar, Saima; Del Río, José Antonio; Díez, Juana; Shomroni, Orr; Kanata, Eirini; Thüne, Katrin

doi:10.1371/journal.ppat.1006802

Items
Marc 21

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024	7	_	\|a 10.1371/journal.ppat.1006802 \|2 doi
024	7	_	\|a pmid:29357384 \|2 pmid
024	7	_	\|a pmc:PMC5794191 \|2 pmc
024	7	_	\|a 1553-7366 \|2 ISSN
024	7	_	\|a 1553-7374 \|2 ISSN
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037	_	_	\|a DZNE-2020-06092
041	_	_	\|a English
082	_	_	\|a 610
100	1	_	\|a Llorens, Franc \|0 P:(DE-HGF)0 \|b 0 \|e Corresponding author
245	_	_	\|a Regional and subtype-dependent miRNA signatures in sporadic Creutzfeldt-Jakob disease are accompanied by alterations in miRNA silencing machinery and biogenesis.
260	_	_	\|a Lawrence, Kan. \|c 2018 \|b PLoS
264	_	1	\|3 online \|2 Crossref \|b Public Library of Science (PLoS) \|c 2018-01-22
336	7	_	\|a article \|2 DRIVER
336	7	_	\|a Output Types/Journal article \|2 DataCite
336	7	_	\|a Journal Article \|b journal \|m journal \|0 PUB:(DE-HGF)16 \|s 1602761456_13710 \|2 PUB:(DE-HGF)
336	7	_	\|a ARTICLE \|2 BibTeX
336	7	_	\|a JOURNAL_ARTICLE \|2 ORCID
336	7	_	\|a Journal Article \|0 0 \|2 EndNote
520	_	_	\|a 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.
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536	_	_	\|a 342 - Disease Mechanisms and Model Systems (POF3-342) \|0 G:(DE-HGF)POF3-342 \|c POF3-342 \|f POF III \|x 1
542	_	_	\|i 2018-01-22 \|2 Crossref \|u http://creativecommons.org/licenses/by/4.0/
588	_	_	\|a Dataset connected to CrossRef, PubMed,
650	_	7	\|a MicroRNAs \|2 NLM Chemicals
650	_	2	\|a Adult \|2 MeSH
650	_	2	\|a Aged \|2 MeSH
650	_	2	\|a Aged, 80 and over \|2 MeSH
650	_	2	\|a Brain: metabolism \|2 MeSH
650	_	2	\|a Brain: pathology \|2 MeSH
650	_	2	\|a Case-Control Studies \|2 MeSH
650	_	2	\|a Creutzfeldt-Jakob Syndrome: classification \|2 MeSH
650	_	2	\|a Creutzfeldt-Jakob Syndrome: genetics \|2 MeSH
650	_	2	\|a Creutzfeldt-Jakob Syndrome: pathology \|2 MeSH
650	_	2	\|a Female \|2 MeSH
650	_	2	\|a Gene Expression Profiling \|2 MeSH
650	_	2	\|a Humans \|2 MeSH
650	_	2	\|a Male \|2 MeSH
650	_	2	\|a MicroRNAs: biosynthesis \|2 MeSH
650	_	2	\|a MicroRNAs: genetics \|2 MeSH
650	_	2	\|a Middle Aged \|2 MeSH
650	_	2	\|a RNA Interference \|2 MeSH
650	_	2	\|a Transcriptome \|2 MeSH
700	1	_	\|a Thüne, Katrin \|0 P:(DE-2719)2811840 \|b 1 \|u dzne
700	1	_	\|a Martí, Eulàlia \|b 2
700	1	_	\|a Kanata, Eirini \|b 3
700	1	_	\|a Dafou, Dimitra \|b 4
700	1	_	\|a Díaz-Lucena, Daniela \|b 5
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700	1	_	\|a Michel, Uwe \|0 P:(DE-HGF)0 \|b 10
700	1	_	\|a Fernández-Borges, Natalia \|b 11
700	1	_	\|a Andréoletti, Olivier \|b 12
700	1	_	\|a Del Río, José Antonio \|b 13
700	1	_	\|a Díez, Juana \|b 14
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700	1	_	\|a Bonn, Stefan \|0 P:(DE-2719)2810547 \|b 16 \|u dzne
700	1	_	\|a Sklaviadis, Theodoros \|b 17
700	1	_	\|a Torres, Juan Maria \|b 18
700	1	_	\|a Ferrer, Isidre \|b 19
700	1	_	\|a Zerr, Inga \|0 P:(DE-2719)2000058 \|b 20 \|e Last author \|u dzne
773	1	8	\|a 10.1371/journal.ppat.1006802 \|b : Public Library of Science (PLoS), 2018-01-22 \|n 1 \|p e1006802 \|3 journal-article \|2 Crossref \|t PLOS Pathogens \|v 14 \|y 2018 \|x 1553-7374
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999	C	5	\|9 -- missing cx lookup -- \|a 10.1111/bpa.12267 \|2 Crossref \|o 10.1111/bpa.12267
999	C	5	\|9 -- missing cx lookup -- \|a 10.1523/JNEUROSCI.1997-12.2013 \|2 Crossref \|o 10.1523/JNEUROSCI.1997-12.2013
999	C	5	\|9 -- missing cx lookup -- \|a 10.1016/j.brainresbull.2012.05.018 \|2 Crossref \|o 10.1016/j.brainresbull.2012.05.018
999	C	5	\|9 -- missing cx lookup -- \|a 10.1111/j.1750-3639.1998.tb00176.x \|2 Crossref \|o 10.1111/j.1750-3639.1998.tb00176.x
999	C	5	\|9 -- missing cx lookup -- \|a 10.1016/j.conb.2009.05.015 \|2 Crossref \|o 10.1016/j.conb.2009.05.015
999	C	5	\|9 -- missing cx lookup -- \|a 10.1093/nar/gkw550 \|2 Crossref \|o 10.1093/nar/gkw550
999	C	5	\|9 -- missing cx lookup -- \|a 10.1038/nrg.2016.134 \|2 Crossref \|o 10.1038/nrg.2016.134
999	C	5	\|9 -- missing cx lookup -- \|a 10.3109/1354750X.2013.814073 \|2 Crossref \|o 10.3109/1354750X.2013.814073
999	C	5	\|9 -- missing cx lookup -- \|a 10.1261/rna.036863.112 \|2 Crossref \|o 10.1261/rna.036863.112
999	C	5	\|9 -- missing cx lookup -- \|a 10.1097/NEN.0000000000000176 \|2 Crossref \|o 10.1097/NEN.0000000000000176
999	C	5	\|9 -- missing cx lookup -- \|a 10.1093/brain/awp191 \|2 Crossref \|o 10.1093/brain/awp191
999	C	5	\|9 -- missing cx lookup -- \|a 10.1007/s004390051096 \|2 Crossref \|o 10.1007/s004390051096
999	C	5	\|9 -- missing cx lookup -- \|a 10.1016/j.molcel.2010.05.004 \|2 Crossref \|o 10.1016/j.molcel.2010.05.004
999	C	5	\|9 -- missing cx lookup -- \|a 10.1038/nprot.2016.120 \|2 Crossref \|o 10.1038/nprot.2016.120
999	C	5	\|y 2015 \|2 Crossref \|o M Schmitz 2015

Library	Collection	CLSMajor	CLSMinor	Language	Author

Marc 21

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