Animal Models of MS Reveal Multiple Roles of Microglia in Disease Pathogenesis.

Multiple sclerosis (MS) is a progressive inflammatory and demyelinating disease that affects more than 2.5 million people worldwide every year. Current therapies use mostly disease-modifying drugs, focusing on blocking and regulating systemic functions and the central nervous system (CNS) infiltration of immune cells; however, these therapies only attenuate or delay MS symptoms, but are not effective in halting the disease progression. More recent evidence indicated that regulation of inflammation within the CNS might be a better way to approach the treatment of the disease and microglia, the resident immune cells, may be a promising target of therapeutic studies. Microglia activation classically accompanies MS development, and regulation of microglia function changes the outcome of the disease. In this paper, we review the contributions of microglia to MS pathogenesis and discuss microglial functions in antigen presentation, cytokine release, and phagocytosis. We describe data both from animal and human studies. The significant impact of the timing, intensity, and differentiation fate of activated microglia is discussed, as they can modulate MS outcomes and potentially be critically modified for future therapeutic studies.