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MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration

2021-11-27Journal article Open access
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dc.contributor.authorWallach, Thomas
dc.contributor.authorMossmann, Zoé J.
dc.contributor.authorSzczepek, Michal
dc.contributor.authorWetzel, Max
dc.contributor.authorMachado, Rui
dc.contributor.authorRaden, Martin
dc.contributor.authorMiladi, Milad
dc.contributor.authorKleinau, Gunnar
dc.contributor.authorKrüger, Christina
dc.contributor.authorDembny, Paul
dc.contributor.authorAdler, Drew
dc.contributor.authorZhai, Yuanyuan
dc.contributor.authorKumbol, Victor
dc.contributor.authorDzaye, Omar
dc.contributor.authorSchüler, Jutta
dc.contributor.authorFutschik, Matthias
dc.contributor.authorBackofen, Rolf
dc.contributor.authorScheerer, Patrick
dc.contributor.authorLehnardt, Seija
dc.date.accessioned2021-12-15T10:47:54Z
dc.date.available2021-12-15T10:47:54Z
dc.date.issued2021-11-27
dc.description.abstractBackground: MicroRNA (miRNA) expression in the brain is altered in neurodegenerative diseases. Recent studies demonstrated that selected miRNAs conventionally regulating gene expression at the post-transcriptional level can act extracellularly as signaling molecules. The identity of miRNA species serving as membrane receptor ligands involved in neuronal apoptosis in the central nervous system (CNS), as well as the miRNAs’ sequence and structure required for this mode of action remained largely unresolved. Methods: Using a microarray-based screening approach we analyzed apoptotic cortical neurons of C56BL/6 mice and their supernatant with respect to alterations in miRNA expression/presence. HEK-Blue Toll-like receptor (TLR) 7/8 reporter cells, primary microglia and macrophages derived from human and mouse were employed to test the potential of the identified miRNAs released from apoptotic neurons to serve as signaling molecules for the RNAsensing receptors. Biophysical and bioinformatical approaches, as well as immunoassays and sequential microscopy were used to analyze the interaction between candidate miRNA and TLR. Immunocytochemical and -histochemical analyses of murine CNS cultures and adult mice intrathecally injected with miRNAs, respectively, were performed to evaluate the impact of miRNA-induced TLR activation on neuronal survival and microglial activation.pt_PT
dc.description.sponsorshipDFG, NeuroCure Exc 257, LE 2420/2–1, SFB-TRR 167/B03 to S.L.; BA 2168/16–1, BA 2168/21–1, and BA 2168/3–3 to R.B.); (CIBSSEXC-2189-Project ID 390939984); CRC 1078/B6; CRC 1423, project number 421152132, subprojects A01, A05, Z03; through CRC 1365, project number 394046635, subproject A03, and through Germany’s Excellence Strategy-EXC 2008/1 (UniSysCat)— 390540038.
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1186/s13024-021-00498-5pt_PT
dc.identifier.eissn1750-1326
dc.identifier.urihttp://hdl.handle.net/10400.1/17388
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBMCpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectExtracellular microRNAspt_PT
dc.subjectEndogenous Toll-like receptor ligandspt_PT
dc.subjectCortical neuronspt_PT
dc.subjectNeuronal apoptosispt_PT
dc.subjectMicrogliapt_PT
dc.subjectNeurodegenerationpt_PT
dc.subjectmiRNA microarraypt_PT
dc.titleMicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegenerationpt_PT
dc.title.alternativeMicroRNA-100-5p e microRNA-298-5p liberados de neurônios corticais apoptóticos são receptor endógeno tipo Toll 7/8 ligantes que contribuem para a neurodegeneraçãopt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue1pt_PT
oaire.citation.titleMolecular Neurodegenerationpt_PT
oaire.citation.volume16pt_PT
person.familyNameMachado
person.familyNameFutschik
person.givenNameRui
person.givenNameMatthias
person.identifier.ciencia-id5D19-8F5F-3CE1
person.identifier.ciencia-idA71B-AD01-3501
person.identifier.orcid0000-0002-4080-2353
person.identifier.orcid0000-0002-6245-8071
person.identifier.scopus-author-id55991033900
person.identifier.scopus-author-id14017989400
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication7786b5c6-964b-4322-8a4e-920652e66880
relation.isAuthorOfPublicationd58f3269-c7e1-4c22-b094-5cfe6750821b
relation.isAuthorOfPublication.latestForDiscoveryd58f3269-c7e1-4c22-b094-5cfe6750821b

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