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microRNA-132 regulates gene expression programs involved in microglial homeostasis

Onderzoeksgroep Salta
Publicatiejaar 2023
Gepubliceerd in iScience
Auteur(s) Hannah Walgrave, Amber Penning, Giorgia Tosoni, Sarah Snoeck, Kristofer Davie, Emma Davis, Leen Wolfs, Annerieke Sierksma, Mayte Mars, Taofeng Bu, Nicola Thrupp, Lujia Zhou, Diederik Moechars, Renzo Mancuso, Mark Fiers, Andrew J M Howden, Bart De Strooper, Evgenia Salta

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.

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