Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer’s disease
dc.rights.license | open | en_US |
dc.contributor.author | YIN, Zhuoran | |
dc.contributor.author | HERRON, Shawn | |
dc.contributor.author | SILVEIRA, Sebastian | |
dc.contributor.author | KLEEMANN, Kilian | |
dc.contributor.author | GAUTHIER, Christian | |
dc.contributor.author | MALLAH, Dania | |
dc.contributor.author | CHENG, Yiran | |
dc.contributor.author | MARGETA, Milica A. | |
dc.contributor.author | PITTS, Kristen M. | |
dc.contributor.author | BARRY, Jen-Li | |
dc.contributor.author | SUBRAMANIAN, Ayshwarya | |
dc.contributor.author | SHOREY, Hannah | |
dc.contributor.author | BRANDAO, Wesley | |
dc.contributor.author | DURAO, Ana | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | DELPECH, Jean-Christophe | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | MADORE, Charlotte | |
dc.contributor.author | JEDRYCHOWSKI, Mark | |
dc.contributor.author | AJAY, Amrendra K. | |
dc.contributor.author | MURUGAIYAN, Gopal | |
dc.contributor.author | HERSH, Samuel W. | |
dc.contributor.author | IKEZU, Seiko | |
dc.contributor.author | IKEZU, Tsuneya | |
dc.contributor.author | BUTOVSKY, Oleg | |
dc.date.accessioned | 2023-10-03T13:32:54Z | |
dc.date.available | 2023-10-03T13:32:54Z | |
dc.date.issued | 2023-06-08 | |
dc.identifier.issn | 1097-6256 | en_US |
dc.identifier.uri | oai:crossref.org:10.1038/s41593-023-01355-y | |
dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/183866 | |
dc.description.abstractEn | Microglia play a critical role in brain homeostasis and disease progression. In neurodegenerative conditions, microglia acquire the neurodegenerative phenotype (MGnD), whose function is poorly understood. MicroRNA-155 (miR-155), enriched in immune cells, critically regulates MGnD. However, its role in Alzheimer’s disease (AD) pathogenesis remains unclear. Here, we report that microglial deletion of miR-155 induces a pre-MGnD activation state via interferon-γ (IFN-γ) signaling, and blocking IFN-γ signaling attenuates MGnD induction and microglial phagocytosis. Single-cell RNA-sequencing analysis of microglia from an AD mouse model identifies Stat1 and Clec2d as pre-MGnD markers. This phenotypic transition enhances amyloid plaque compaction, reduces dystrophic neurites, attenuates plaque-associated synaptic degradation and improves cognition. Our study demonstrates a miR-155-mediated regulatory mechanism of MGnD and the beneficial role of IFN-γ-responsive pre-MGnD in restricting neurodegenerative pathology and preserving cognitive function in an AD mouse model, highlighting miR-155 and IFN-γ as potential therapeutic targets for AD. | |
dc.language.iso | EN | en_US |
dc.source | crossref | |
dc.title.en | Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer’s disease | |
dc.type | Article de revue | en_US |
dc.identifier.doi | 10.1038/s41593-023-01355-y | en_US |
dc.subject.hal | Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC] | en_US |
dc.identifier.pubmed | 37291336 | en_US |
bordeaux.journal | Nature Neuroscience | en_US |
bordeaux.page | 1196-1207 | en_US |
bordeaux.volume | 26 | en_US |
bordeaux.hal.laboratories | NutriNeuro (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286 | en_US |
bordeaux.issue | 7 | en_US |
bordeaux.institution | Université de Bordeaux | en_US |
bordeaux.institution | Bordeaux INP | en_US |
bordeaux.institution | INRAE | en_US |
bordeaux.peerReviewed | oui | en_US |
bordeaux.inpress | non | en_US |
bordeaux.import.source | dissemin | |
hal.identifier | hal-04227164 | |
hal.version | 1 | |
hal.date.transferred | 2023-10-03T13:32:57Z | |
hal.popular | non | en_US |
hal.audience | Internationale | en_US |
hal.export | true | |
workflow.import.source | dissemin | |
dc.rights.cc | Pas de Licence CC | en_US |
bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature%20Neuroscience&rft.date=2023-06-08&rft.volume=26&rft.issue=7&rft.spage=1196-1207&rft.epage=1196-1207&rft.eissn=1097-6256&rft.issn=1097-6256&rft.au=YIN,%20Zhuoran&HERRON,%20Shawn&SILVEIRA,%20Sebastian&KLEEMANN,%20Kilian&GAUTHIER,%20Christian&rft.genre=article |
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