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Publication : microRNA-132 regulates gene expression programs involved in microglial homeostasis.

First Author  Walgrave H Year  2023
Journal  iScience Volume  26
Issue  6 Pages  106829
PubMed ID  37250784 Mgi Jnum  J:351232
Mgi Id  MGI:7487563 Doi  10.1016/j.isci.2023.106829
Citation  Walgrave H, et al. (2023) microRNA-132 regulates gene expression programs involved in microglial homeostasis. iScience 26(6):106829
abstractText  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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