Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (10): 4633-4641.doi: 10.4103/NRR.NRR-D-25-01298

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

Haiwei Zhang1, 2, Mengmeng Jin3, Peng Jiang3, Ying Liu1, 2, *   

  1. 1Center for Translational Science, Florida International University, SW Village Pkwy, Port St. Lucie, FL, USA; 
    2Department of Cell Biology and Neuroscience, Rutgers University, New Brunswick, Piscataway, NJ, USA
  • Online:2026-10-15 Published:2026-06-11
  • Contact: Ying Liu, PhD, liuyin@fiu.edu.
  • Supported by:
    This work was supported by NIH R01 NS110707, FIU startup fund (to YL).

Abstract: 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.

Key words: energy metabolism, functional states, human induced pluripotent stem cells, lipid metabolism, metabolic reprogramming, microglia, neurodegenerative disease, neuroinflammation