miRNAs in Microglia: Important Players in Multiple Sclerosis Pathology

Abstract

Microglia are the resident immune cells of the central nervous system and important regulators of brain homeostasis. Central to this role is a dynamic phenotypic plasticity that enables microglia to respond to environmental and pathological stimuli. Importantly, different microglial phenotypes can be both beneficial and detrimental to central nervous system health. Chronically activated inflammatory microglia are a hallmark of neurodegeneration, including the autoimmune disease multiple sclerosis (MS). By contrast, microglial phagocytosis of myelin debris is essential for resolving inflammation and promoting remyelination. As such, microglia are being explored as a potential therapeutic target for MS. MicroRNAs (miRNAs) are short non-coding ribonucleic acids that regulate gene expression and act as master regulators of cellular phenotype and function. Dysregulation of certain miRNAs can aberrantly activate and promote specific polarisation states in microglia to modulate their activity in inflammation and neurodegeneration. In addition, miRNA dysregulation is implicated in MS pathogenesis, with circulating biomarkers and lesion specific miRNAs identified as regulators of inflammation and myelination. However, the role of miRNAs in microglia that specifically contribute to MS progression are still largely unknown. miRNAs are being explored as therapeutic agents, providing an opportunity to modulate microglial function in neurodegenerative diseases such as MS. This review will focus firstly on elucidating the complex role of microglia in MS pathogenesis. Secondly, we explore the essential roles of miRNAs in microglial function. Finally, we focus on miRNAs that are implicated in microglial processes that contribute directly to MS pathology, prioritising targets that could inform novel therapeutic approaches to MS.