Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy

Microglia are the resident macrophages of the central nervous system (CNS) acting as the first line of defense in the brain by phagocytosing harmful pathogens and cellular debris. Microglia emerge from early erythromyeloid progenitors of the yolk sac and enter the developing brain before the establishment of a fully mature blood-brain barrier. In physiological conditions, during brain development, microglia contribute to CNS homeostasis by supporting cell proliferation of neural precursors. In post-natal life, such cells contribute to preserving the integrity of neuronal circuits by sculpting synapses. After a CNS injury, microglia change their morphology and down-regulate those genes supporting homeostatic functions. However, it is still unclear whether such changes are accompanied by molecular and functional modifications that might contribute to the pathological process. While comprehensive transcriptome analyses at the single-cell level have identified specific gene perturbations occurring in the pathological microglia, still the precise protective/detrimental role of microglia in neurological disorders is far from being fully elucidated. In this review, the results so far obtained regarding the role of microglia in neurodegenerative disorders will be discussed. There is solid and sound evidence suggesting that regulating microglia functions during disease pathology might represent a strategy to develop future therapies aimed at counteracting brain degeneration in multiple sclerosis, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

Automated summary

Microglia are resident macrophages of the central nervous system, playing a crucial role in immune defense in the brain. They support cell proliferation of neural precursors during brain development and preserve the integrity of neuronal circuits by sculpting synapses in post-natal life. Their functions change after CNS injury, but the precise role in neurological disorders is still not fully understood. There is evidence suggesting that regulating microglia functions could be a potential strategy for future therapies in neurodegenerative disorders such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.