The Dual Role of Microglia in Multiple Sclerosis and its Implications for Diagnostics and Repair

Microglia play a crucial role in the development, immune surveillance, and repair of the central nervous system. These cells play a multifaceted role in multiple sclerosis (MS), with evidence suggesting that microglia can promote both active inflammation and remyelination. For instance, it has been shown that microglia can support the development of oligodendrocytes and phagocytose myelin debris, thus aiding in proper remyelination. However, microglia overactivation in MS lesions exacerbates neuroinflammation by releasing inflammatory cytokines and facilitating the activation of astrocytes and immune cells, promoting demyelination and, ultimately, driving MS pathology. In fact, it has been shown that there is a correlation between activated microglia patterns and the chronicity of MS. Thus, although it is difficult to be certain whether these cells are friends or foes, there is no doubt that microglia will be a relevant target for MS diagnosis and treatment in the future, when further research will help to clarify the role of these cells in MS. MRI and PET scan allow evaluation of microglia/macrophages biomarkers, facilitating the clinical assessment of a patient's disease stage. Moreover, new microglia-specific markers are being discovered, which will increase diagnostic precision, helping to identify active and chronic MS lesions. Because microglia are involved in all MS phases, these cells are also an important drug target. In this review, we focus on the current understanding of the role of microglia in MS progression as well as on the evidence supporting both inflammatory and reparative functions of these cells. We will also review how microglia may yield new biomarkers for MS diagnosis and serve as a potential target for therapy.