Microglia regulation of central nervous system myelin health and regeneration

Microglia are increasingly implicated in the maintenance and regeneration of myelin, which is damaged with normal ageing and in several neurodegenerative diseases. This article reviews the mechanisms by which microglia support and restore myelin health and the factors that influence these crucial microglial functions. Microglia are resident macrophages of the central nervous system that have key functions in its development, homeostasis and response to damage and infection. Although microglia have been increasingly implicated in contributing to the pathology that underpins neurological dysfunction and disease, they also have crucial roles in neurological homeostasis and regeneration. This includes regulation of the maintenance and regeneration of myelin, the membrane that surrounds neuronal axons, which is required for axonal health and function. Myelin is damaged with normal ageing and in several neurodegenerative diseases, such as multiple sclerosis and Alzheimer disease. Given the lack of approved therapies targeting myelin maintenance or regeneration, it is imperative to understand the mechanisms by which microglia support and restore myelin health to identify potential therapeutic approaches. However, the mechanisms by which microglia regulate myelin loss or integrity are still being uncovered. In this Review, we discuss recent work that reveals the changes in white matter with ageing and neurodegenerative disease, how this relates to microglia dynamics during myelin damage and regeneration, and factors that influence the regenerative functions of microglia.

Automated summary

This article reviews the role of microglia in the maintenance and regeneration of myelin, which is damaged in normal aging and neurodegenerative diseases. Microglia, as resident macrophages of the central nervous system, have key functions in development, homeostasis, and response to damage and infection. Understanding the mechanisms by which microglia support and restore myelin health is essential for identifying potential therapeutic approaches for myelin-related diseases.