001     284348
005     20260212105835.0
024 7 _ |a 10.1186/s12974-025-03680-4
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024 7 _ |a pmid:41514337
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024 7 _ |a pmc:PMC12849500
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037 _ _ |a DZNE-2026-00119
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a McGurran, Hugo
|b 0
245 _ _ |a MicroRNA-29a-5p contributes to neuroinflammation through TLR7.
260 _ _ |a London
|c 2026
|b BioMed Central
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
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650 _ 7 |a Alzheimer’s disease
|2 Other
650 _ 7 |a Cytokine expression
|2 Other
650 _ 7 |a MicroRNA
|2 Other
650 _ 7 |a Microglia
|2 Other
650 _ 7 |a Neuroinflammation
|2 Other
650 _ 7 |a Toll-like receptors
|2 Other
650 _ 7 |a MicroRNAs
|2 NLM Chemicals
650 _ 7 |a Toll-Like Receptor 7
|2 NLM Chemicals
650 _ 7 |a Tlr7 protein, mouse
|2 NLM Chemicals
650 _ 7 |a MIRN29 microRNA, mouse
|2 NLM Chemicals
650 _ 7 |a Membrane Glycoproteins
|2 NLM Chemicals
650 _ 7 |a MIRN29a microRNA, human
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a MicroRNAs: metabolism
|2 MeSH
650 _ 2 |a MicroRNAs: genetics
|2 MeSH
650 _ 2 |a MicroRNAs: administration & dosage
|2 MeSH
650 _ 2 |a Toll-Like Receptor 7: metabolism
|2 MeSH
650 _ 2 |a Toll-Like Receptor 7: genetics
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Neuroinflammatory Diseases: metabolism
|2 MeSH
650 _ 2 |a Neuroinflammatory Diseases: genetics
|2 MeSH
650 _ 2 |a Neuroinflammatory Diseases: pathology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a Membrane Glycoproteins: metabolism
|2 MeSH
650 _ 2 |a Membrane Glycoproteins: genetics
|2 MeSH
650 _ 2 |a Cells, Cultured
|2 MeSH
650 _ 2 |a Male
|2 MeSH
700 1 _ |a Graceffo, Eugenio
|b 1
700 1 _ |a Kumbol, Victor
|b 2
700 1 _ |a Jendrach, Marina
|b 3
700 1 _ |a Hinkelmann, Lukas
|b 4
700 1 _ |a Brehm, Mariam
|b 5
700 1 _ |a Ravatt, Leandre
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700 1 _ |a Krüger, Christina
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700 1 _ |a Wallach, Thomas
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700 1 _ |a Haake, Alexander
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700 1 _ |a Wegmann, Susanne
|0 P:(DE-2719)2812695
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700 1 _ |a Heppner, Frank L
|0 P:(DE-2719)2812386
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700 1 _ |a Schülke, Markus
|b 12
700 1 _ |a Lehnardt, Seija
|b 13
773 _ _ |a 10.1186/s12974-025-03680-4
|g Vol. 23, no. 1, p. 38
|0 PERI:(DE-600)2156455-3
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|p 38
|t Journal of neuroinflammation
|v 23
|y 2026
|x 1742-2094
856 4 _ |u https://pub.dzne.de/record/284348/files/DZNE-2026-00119%20SUP.zip
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