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microRNA-132 regulates gene expression programs involved in microglial homeostasis

Walgrave, H; Penning, A; Tosoni, G; Snoeck, S; Davie, K; Davis, E; Wolfs, L; ... Salta, E; + view all (2023) microRNA-132 regulates gene expression programs involved in microglial homeostasis. iScience , 26 (6) , Article 106829. 10.1016/j.isci.2023.106829. Green open access

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Abstract

microRNA-132 (miR-132), a known neuronal regulator, is one of the most robustly downregulated microRNAs (miRNAs) in the brain of Alzheimer's disease (AD) patients. Increasing miR-132 in AD mouse brain ameliorates amyloid and Tau pathologies, and also restores adult hippocampal neurogenesis and memory deficits. However, the functional pleiotropy of miRNAs requires in-depth analysis of the effects of miR-132 supplementation before it can be moved forward for AD therapy. We employ here miR-132 loss- and gain-of-function approaches using single-cell transcriptomics, proteomics, and in silico AGO-CLIP datasets to identify molecular pathways targeted by miR-132 in mouse hippocampus. We find that miR-132 modulation significantly affects the transition of microglia from a disease-associated to a homeostatic cell state. We confirm the regulatory role of miR-132 in shifting microglial cell states using human microglial cultures derived from induced pluripotent stem cells.

Type: Article
Title: microRNA-132 regulates gene expression programs involved in microglial homeostasis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.isci.2023.106829
Publisher version: https://doi.org/10.1016/j.isci.2023.106829
Language: English
Additional information: © 2023 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Molecular biology, Neuroscience, Omics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UK Dementia Research Institute HQ
URI: https://discovery.ucl.ac.uk/id/eprint/10171367
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