Microglia-derived exosomes modulate myelin regeneration via activating Nrf2 signaling pathway in oligodendrocyte precursor cells in MS.

Abstract

Demyelination is a prominent feature of multiple sclerosis (MS), where the ability of damaged areas to regenerate myelin is limited. Oligodendrocyte precursor cells (OPCs) accumulate in these areas but struggle to mature into oligodendrocytes (OLGs). Microglia also gather at the lesion site, but their impact on OPCs differentiation is not well understood. Here, we found that miR-155-5p was significantly elevated in the expression profile of exosomes extracted from activated microglia. This miRNA binds to the 3' UTR of the transcription factor Nrf2 in OPCs, inhibiting their differentiation. In a mouse model of demyelination induced by cuprizone, inhibiting miR-155-5p 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.