284348 20260212105835.0 10.1186/s12974-025-03680-4 doi pmid:41514337 pmid pmc:PMC12849500 pmc DZNE-2026-00119 English 610 McGurran, Hugo 0 MicroRNA-29a-5p contributes to neuroinflammation through TLR7. London 2026 BioMed Central article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1770812138_18489 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote MicroRNAs (miRNAs) canonically regulate post-transcriptional gene expression, but they can also serve as ligands for Toll-like receptors (TLRs). These receptors and their associated signalling pathways contribute to inflammatory responses involved in various central nervous system (CNS) diseases, including Alzheimer's disease (AD). Here, we investigated the effects of extracellularly delivered miRNA in the context of neuroinflammation. We identified several miRNAs specifically dysregulated in AD and/or neuroinflammatory states, which directly activate the single-stranded RNA sensors mouse TLR7 and human TLR7/8. Among them, extracellular miR-29a-5p induced cytokine and chemokine release from murine primary microglia, altered expression of TLR signalling elements, and enhanced Aβ phagocytosis. Furthermore, this miRNA induced neuronal injury dependent on microglial TLR7 expression, but also in a cell-autonomous fashion, in vitro. Intrathecal injection of miR-29a-5p into mice led to microglial accumulation and neuronal injury in the cerebral cortex through TLR7 after 3 days. Brains of wild-type and APP/PS1 mice, an established AD mouse model, treated with multiple intrathecal miR-29a-5p injections over 120 days exhibited changes in cytokine/chemokine expression and neuronal injury. RNAseq analysis of the cerebral cortex of both miRNA-treated genotypes revealed downregulation of MAPK-associated pathways.Our study establishes AD-associated miRNAs such as miR-29a-5p as TLR7 agonists and signalling molecules for microglia, thereby altering the neuroinflammatory response. 352 - Disease Mechanisms (POF4-352) G:(DE-HGF)POF4-352 POF4-352 POF IV 0 353 - Clinical and Health Care Research (POF4-353) G:(DE-HGF)POF4-353 POF4-353 POF IV 1 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Alzheimer’s disease Other Cytokine expression Other MicroRNA Other Microglia Other Neuroinflammation Other Toll-like receptors Other MicroRNAs NLM Chemicals Toll-Like Receptor 7 NLM Chemicals Tlr7 protein, mouse NLM Chemicals MIRN29 microRNA, mouse NLM Chemicals Membrane Glycoproteins NLM Chemicals MIRN29a microRNA, human NLM Chemicals Animals MeSH MicroRNAs: metabolism MeSH MicroRNAs: genetics MeSH MicroRNAs: administration & dosage MeSH Toll-Like Receptor 7: metabolism MeSH Toll-Like Receptor 7: genetics MeSH Mice MeSH Neuroinflammatory Diseases: metabolism MeSH Neuroinflammatory Diseases: genetics MeSH Neuroinflammatory Diseases: pathology MeSH Humans MeSH Microglia: metabolism MeSH Mice, Transgenic MeSH Mice, Inbred C57BL MeSH Alzheimer Disease: metabolism MeSH Alzheimer Disease: pathology MeSH Alzheimer Disease: genetics MeSH Membrane Glycoproteins: metabolism MeSH Membrane Glycoproteins: genetics MeSH Cells, Cultured MeSH Male MeSH Graceffo, Eugenio 1 Kumbol, Victor 2 Jendrach, Marina 3 Hinkelmann, Lukas 4 Brehm, Mariam 5 Ravatt, Leandre P:(DE-2719)9001996 6 dzne Krüger, Christina 7 Wallach, Thomas 8 Haake, Alexander P:(DE-2719)9002731 9 dzne Wegmann, Susanne P:(DE-2719)2812695 10 dzne Heppner, Frank L P:(DE-2719)2812386 11 dzne Schülke, Markus 12 Lehnardt, Seija 13 10.1186/s12974-025-03680-4 Vol. 23, no. 1, p. 38 PERI:(DE-600)2156455-3 1 38 Journal of neuroinflammation 23 2026 1742-2094 http://pub.dzne.de/record/284348/files/DZNE-2026-00119%20SUP.zip OpenAccess http://pub.dzne.de/record/284348/files/DZNE-2026-00119.pdf OpenAccess pdfa http://pub.dzne.de/record/284348/files/DZNE-2026-00119.pdf?subformat=pdfa oai:pub.dzne.de:284348 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 6 P:(DE-2719)9001996 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 9 P:(DE-2719)9002731 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 10 P:(DE-2719)2812695 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 11 P:(DE-2719)2812386 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-352 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Disease Mechanisms 0 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-353 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Clinical and Health Care Research 1 2026 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2024-12-16 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2024-12-16 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2024-12-16 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2024-12-16 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2024-12-16 OpenAccess StatID:(DE-HGF)0510 StatID JCR StatID:(DE-HGF)0100 StatID J NEUROINFLAMM : 2022 2024-12-16 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2024-04-10T15:42:04Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2024-04-10T15:42:04Z DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2024-12-16 Fees StatID:(DE-HGF)0700 StatID 2024-12-16 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2024-12-16 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2024-12-16 Peer Review StatID:(DE-HGF)0030 StatID ASC 2024-12-16 Article Processing Charges StatID:(DE-HGF)0561 StatID 2024-12-16 IF >= 5 StatID:(DE-HGF)9905 StatID J NEUROINFLAMM : 2022 2024-12-16 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2024-12-16 Creative Commons Attribution CC BY 4.0 LIC:(DE-HGF)CCBY4 HGFVOC DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2024-12-16 I:(DE-2719)1810006 AG Wegmann Protein Actions in Neurodegeneration 0 I:(DE-2719)1810007 AG Heppner Neuroimmunology 1 journal VDB UNRESTRICTED I:(DE-2719)1810006 I:(DE-2719)1810007 FullTexts