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33 reviewsABSTRACTKeywords:Demyelination is a prominent feature of multiple sclerosis (MS), where the ability of damaged areas to regenerate Demyelinating diseasemyelin is limited. Oligodendrocyte precursor cells (OPCs) accumulate in these areas but struggle to mature into OPCsoligodendrocytes (OLGs). Microglia also gather at the lesion site, but their impact on OPCs differentiation is not Microgliawell understood. Here, we found that miR-155-5p was significantly elevated in the expression profile of exoExosomessomes extracted from activated microglia. This miRNA binds to the 3′ UTR of the transcription factor Nrf2 in miR-155-5pOPCs, inhibiting their differentiation. In a mouse model of demyelination induced by cuprizone, inhibiting miR155-5p in microglia led to improved motor function recovery, increased the number of mature oligodendrocytes and promoted remyelination. In this study, we highlight a potential new target for treating demyelinating diseases.