Beneficial vs. pathogenic microglia functions across aging, multiple sclerosis, and Alzheimer’s disease

Abstract Microglia are a population of central nervous system (CNS)-resident macrophages that play key roles in regulating CNS health. Emerging work has revealed a plethora of ways by which microglia monitor and regulate neuronal and glial function in homeostasis. In response to stressors, microglia lose these homeostatic functions to limit injury and promote regeneration. However, with aging and in neurodegenerative diseases such as multiple sclerosis and Alzheimer’s disease, loss of microglial homeostasis can persist, which can contribute to demyelination, failed remyelination, neurodegeneration, and consequent neurological dysfunction. Given the lack of effective therapies for the treatment of aging-related dysfunction or neurodegeneration, it is important to understand the mechanisms by which beneficial microglia functions give way to pathogenic ones to identify putative therapeutic strategies. In this review, we discuss recent work that has revealed novel roles for microglia in homeostasis, and how loss of homeostasis can either promote disease resolution or drive persistent damage and dysfunction in the CNS.