MiR-124 and MiR-155 as Therapeutic Targets in Microglia-Mediated Inflammation in Multiple Sclerosis.

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease associated with demyelination and microglial activation. Significant progress has recently been made in the development of strategies to treat MS with a focus on microglial cells. In response to injury, microglia, a population of mononuclear phagocytic cells, change from quiescent to activated. M1 microglia produce pro-inflammatory cytokines that cause additional injury, thus they are considered neurotoxic microglia. M2 microglia release anti-inflammatory factors that lead to the suppression of inflammatory responses; therefore, they have a neurotrophic phenotype. The balance between M1 and M2 phenotypes is important for nerve recovery. In neurodegenerative diseases, activated microglia are excessively shifted toward M1 or neurotoxic phenotype due to microRNA (miRNA) dysregulation. The miRNA as a class of non-coding RNAs, control the neuroinflammatory process by activation of microglia. The miR-124 is partly responsible for suppressing the neuroprotective and inflammatory processes by preventing microglia activation. Meanwhile, the microRNA 155, which is induced by pro-inflammatory agents in microglia, promotes the inflammatory process. Several studies have shown that in MS pathogenesis, miR-124 as an anti-inflammatory marker is significantly downregulated, while miR-155 shows an increase. In this study, we will investigate the role of miR-124 and miR-155 in the activation and alteration of microglial phenotype. Finding the relationship between microRNAs and glial cells and inflammation in MS may be used as a therapeutic method to reduce the symptoms in MS patients.