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000284348 1001_ $$aMcGurran, Hugo$$b0
000284348 245__ $$aMicroRNA-29a-5p contributes to neuroinflammation through TLR7.
000284348 260__ $$aLondon$$bBioMed Central$$c2026
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000284348 520__ $$aMicroRNAs (miRNAs) canonically regulate post-transcriptional gene expression, but they can also serve as ligands for Toll-like receptors (TLRs). These receptors and their associated signalling pathways contribute to inflammatory responses involved in various central nervous system (CNS) diseases, including Alzheimer's disease (AD). Here, we investigated the effects of extracellularly delivered miRNA in the context of neuroinflammation. We identified several miRNAs specifically dysregulated in AD and/or neuroinflammatory states, which directly activate the single-stranded RNA sensors mouse TLR7 and human TLR7/8. Among them, extracellular miR-29a-5p induced cytokine and chemokine release from murine primary microglia, altered expression of TLR signalling elements, and enhanced Aβ phagocytosis. Furthermore, this miRNA induced neuronal injury dependent on microglial TLR7 expression, but also in a cell-autonomous fashion, in vitro. Intrathecal injection of miR-29a-5p into mice led to microglial accumulation and neuronal injury in the cerebral cortex through TLR7 after 3 days. Brains of wild-type and APP/PS1 mice, an established AD mouse model, treated with multiple intrathecal miR-29a-5p injections over 120 days exhibited changes in cytokine/chemokine expression and neuronal injury. RNAseq analysis of the cerebral cortex of both miRNA-treated genotypes revealed downregulation of MAPK-associated pathways.Our study establishes AD-associated miRNAs such as miR-29a-5p as TLR7 agonists and signalling molecules for microglia, thereby altering the neuroinflammatory response.
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000284348 650_7 $$2Other$$aAlzheimer’s disease
000284348 650_7 $$2Other$$aCytokine expression
000284348 650_7 $$2Other$$aMicroRNA
000284348 650_7 $$2Other$$aMicroglia
000284348 650_7 $$2Other$$aNeuroinflammation
000284348 650_7 $$2Other$$aToll-like receptors
000284348 650_7 $$2NLM Chemicals$$aMicroRNAs
000284348 650_7 $$2NLM Chemicals$$aToll-Like Receptor 7
000284348 650_7 $$2NLM Chemicals$$aTlr7 protein, mouse
000284348 650_7 $$2NLM Chemicals$$aMIRN29 microRNA, mouse
000284348 650_7 $$2NLM Chemicals$$aMembrane Glycoproteins
000284348 650_7 $$2NLM Chemicals$$aMIRN29a microRNA, human
000284348 650_2 $$2MeSH$$aAnimals
000284348 650_2 $$2MeSH$$aMicroRNAs: metabolism
000284348 650_2 $$2MeSH$$aMicroRNAs: genetics
000284348 650_2 $$2MeSH$$aMicroRNAs: administration & dosage
000284348 650_2 $$2MeSH$$aToll-Like Receptor 7: metabolism
000284348 650_2 $$2MeSH$$aToll-Like Receptor 7: genetics
000284348 650_2 $$2MeSH$$aMice
000284348 650_2 $$2MeSH$$aNeuroinflammatory Diseases: metabolism
000284348 650_2 $$2MeSH$$aNeuroinflammatory Diseases: genetics
000284348 650_2 $$2MeSH$$aNeuroinflammatory Diseases: pathology
000284348 650_2 $$2MeSH$$aHumans
000284348 650_2 $$2MeSH$$aMicroglia: metabolism
000284348 650_2 $$2MeSH$$aMice, Transgenic
000284348 650_2 $$2MeSH$$aMice, Inbred C57BL
000284348 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000284348 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000284348 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000284348 650_2 $$2MeSH$$aMembrane Glycoproteins: metabolism
000284348 650_2 $$2MeSH$$aMembrane Glycoproteins: genetics
000284348 650_2 $$2MeSH$$aCells, Cultured
000284348 650_2 $$2MeSH$$aMale
000284348 7001_ $$aGraceffo, Eugenio$$b1
000284348 7001_ $$aKumbol, Victor$$b2
000284348 7001_ $$aJendrach, Marina$$b3
000284348 7001_ $$aHinkelmann, Lukas$$b4
000284348 7001_ $$aBrehm, Mariam$$b5
000284348 7001_ $$0P:(DE-2719)9001996$$aRavatt, Leandre$$b6$$udzne
000284348 7001_ $$aKrüger, Christina$$b7
000284348 7001_ $$aWallach, Thomas$$b8
000284348 7001_ $$0P:(DE-2719)9002731$$aHaake, Alexander$$b9$$udzne
000284348 7001_ $$0P:(DE-2719)2812695$$aWegmann, Susanne$$b10$$udzne
000284348 7001_ $$0P:(DE-2719)2812386$$aHeppner, Frank L$$b11$$udzne
000284348 7001_ $$aSchülke, Markus$$b12
000284348 7001_ $$aLehnardt, Seija$$b13
000284348 773__ $$0PERI:(DE-600)2156455-3$$a10.1186/s12974-025-03680-4$$gVol. 23, no. 1, p. 38$$n1$$p38$$tJournal of neuroinflammation$$v23$$x1742-2094$$y2026
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