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000139770 1001_ $$0P:(DE-HGF)0$$aLlorens, Franc$$b0$$eCorresponding author
000139770 245__ $$aRegional and subtype-dependent miRNA signatures in sporadic Creutzfeldt-Jakob disease are accompanied by alterations in miRNA silencing machinery and biogenesis.
000139770 260__ $$aLawrence, Kan.$$bPLoS$$c2018
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000139770 520__ $$aIncreasing 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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000139770 542__ $$2Crossref$$i2018-01-22$$uhttp://creativecommons.org/licenses/by/4.0/
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000139770 650_7 $$2NLM Chemicals$$aMicroRNAs
000139770 650_2 $$2MeSH$$aAdult
000139770 650_2 $$2MeSH$$aAged
000139770 650_2 $$2MeSH$$aAged, 80 and over
000139770 650_2 $$2MeSH$$aBrain: metabolism
000139770 650_2 $$2MeSH$$aBrain: pathology
000139770 650_2 $$2MeSH$$aCase-Control Studies
000139770 650_2 $$2MeSH$$aCreutzfeldt-Jakob Syndrome: classification
000139770 650_2 $$2MeSH$$aCreutzfeldt-Jakob Syndrome: genetics
000139770 650_2 $$2MeSH$$aCreutzfeldt-Jakob Syndrome: pathology
000139770 650_2 $$2MeSH$$aFemale
000139770 650_2 $$2MeSH$$aGene Expression Profiling
000139770 650_2 $$2MeSH$$aHumans
000139770 650_2 $$2MeSH$$aMale
000139770 650_2 $$2MeSH$$aMicroRNAs: biosynthesis
000139770 650_2 $$2MeSH$$aMicroRNAs: genetics
000139770 650_2 $$2MeSH$$aMiddle Aged
000139770 650_2 $$2MeSH$$aRNA Interference
000139770 650_2 $$2MeSH$$aTranscriptome
000139770 7001_ $$0P:(DE-2719)2811840$$aThüne, Katrin$$b1$$udzne
000139770 7001_ $$aMartí, Eulàlia$$b2
000139770 7001_ $$aKanata, Eirini$$b3
000139770 7001_ $$aDafou, Dimitra$$b4
000139770 7001_ $$aDíaz-Lucena, Daniela$$b5
000139770 7001_ $$aVivancos, Ana$$b6
000139770 7001_ $$0P:(DE-2719)2810755$$aShomroni, Orr$$b7$$udzne
000139770 7001_ $$0P:(DE-2719)9000358$$aZafar, Saima$$b8$$udzne
000139770 7001_ $$0P:(DE-2719)9000287$$aSchmitz, Matthias$$b9$$udzne
000139770 7001_ $$0P:(DE-HGF)0$$aMichel, Uwe$$b10
000139770 7001_ $$aFernández-Borges, Natalia$$b11
000139770 7001_ $$aAndréoletti, Olivier$$b12
000139770 7001_ $$aDel Río, José Antonio$$b13
000139770 7001_ $$aDíez, Juana$$b14
000139770 7001_ $$0P:(DE-2719)2000047$$aFischer, Andre$$b15$$udzne
000139770 7001_ $$0P:(DE-2719)2810547$$aBonn, Stefan$$b16$$udzne
000139770 7001_ $$aSklaviadis, Theodoros$$b17
000139770 7001_ $$aTorres, Juan Maria$$b18
000139770 7001_ $$aFerrer, Isidre$$b19
000139770 7001_ $$0P:(DE-2719)2000058$$aZerr, Inga$$b20$$eLast author$$udzne
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000139770 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.conb.2009.05.015$$o10.1016/j.conb.2009.05.015
000139770 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/gkw550$$o10.1093/nar/gkw550
000139770 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrg.2016.134$$o10.1038/nrg.2016.134
000139770 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3109/1354750X.2013.814073$$o10.3109/1354750X.2013.814073
000139770 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1261/rna.036863.112$$o10.1261/rna.036863.112
000139770 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1097/NEN.0000000000000176$$o10.1097/NEN.0000000000000176
000139770 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/awp191$$o10.1093/brain/awp191
000139770 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s004390051096$$o10.1007/s004390051096
000139770 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.molcel.2010.05.004$$o10.1016/j.molcel.2010.05.004
000139770 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nprot.2016.120$$o10.1038/nprot.2016.120
000139770 999C5 $$2Crossref$$oM Schmitz 2015$$y2015