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@ARTICLE{McGurran:284348,
author = {McGurran, Hugo and Graceffo, Eugenio and Kumbol, Victor and
Jendrach, Marina and Hinkelmann, Lukas and Brehm, Mariam and
Ravatt, Leandre and Krüger, Christina and Wallach, Thomas
and Haake, Alexander and Wegmann, Susanne and Heppner, Frank
L and Schülke, Markus and Lehnardt, Seija},
title = {{M}icro{RNA}-29a-5p contributes to neuroinflammation
through {TLR}7.},
journal = {Journal of neuroinflammation},
volume = {23},
number = {1},
issn = {1742-2094},
address = {London},
publisher = {BioMed Central},
reportid = {DZNE-2026-00119},
pages = {38},
year = {2026},
abstract = {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.},
keywords = {Animals / MicroRNAs: metabolism / MicroRNAs: genetics /
MicroRNAs: administration $\&$ dosage / Toll-Like Receptor
7: metabolism / Toll-Like Receptor 7: genetics / Mice /
Neuroinflammatory Diseases: metabolism / Neuroinflammatory
Diseases: genetics / Neuroinflammatory Diseases: pathology /
Humans / Microglia: metabolism / Mice, Transgenic / Mice,
Inbred C57BL / Alzheimer Disease: metabolism / Alzheimer
Disease: pathology / Alzheimer Disease: genetics / Membrane
Glycoproteins: metabolism / Membrane Glycoproteins: genetics
/ Cells, Cultured / Male / 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)},
cin = {AG Wegmann / AG Heppner},
ddc = {610},
cid = {I:(DE-2719)1810006 / I:(DE-2719)1810007},
pnm = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41514337},
pmc = {pmc:PMC12849500},
doi = {10.1186/s12974-025-03680-4},
url = {https://pub.dzne.de/record/284348},
}