Metabolic reprogramming of microglia: Effects on development, disease, and therapeutic potential

Microglia, the immune sentinels of the central nervous system, play vital roles in maintaining neural homeostasis and mediating responses to injury and disease. Their functions, including synaptic pruning to neuroinflammation, are tightly linked to their metabolic state. Emerging evidence suggests that metabolic reprogramming is a key driver of microglial activation, functional transitions, and interactions with neurons and other glial cells. This review summarizes current findings on the developmental origins, region-specific adaptations, and metabolic plasticity of microglia. We review lipid metabolism, energy utilization, and oxidative stress responses, which underlie immune regulation and neuroprotective functions. By integrating molecular, transcriptomic, and metabolomic insights, we provide a comprehensive understanding of microglial metabolism and highlight potential therapeutic strategies targeting metabolic pathways in neurodegenerative and central nervous system diseases.