Glucose metabolic reprogramming: mechanisms and therapeutic implications in neuroinflammation

Area of Science:

• Neuroscience
• Immunology
• Metabolism

Background:

• Microglia are key immune cells in the central nervous system with dual roles in homeostasis and neuroinflammation.
• Pathological conditions trigger significant metabolic changes in microglia, notably a shift towards aerobic glycolysis.
• The glucose-glycolysis-lactate axis is central to microglial function and immune responses.

Purpose of the Study:

• To review the pivotal role of the glucose-glycolysis-lactate metabolic axis in microglial immunometabolism.
• To elucidate how key glycolytic enzymes and metabolites regulate microglial function.
• To discuss therapeutic strategies targeting microglial glycolytic reprogramming for neuroinflammation.

Main Methods:

• Literature review focusing on microglial immunometabolism.
• Analysis of the role of glycolytic enzymes (e.g., HK2, PKM2) and metabolites (e.g., lactate, pyruvate, ATP).
• Discussion of therapeutic interventions targeting metabolic pathways.

Main Results:

• Microglia exhibit profound glycolytic reprogramming under pathological conditions, shifting from oxidative phosphorylation to aerobic glycolysis.
• Key glycolytic enzymes and metabolites critically regulate microglial functions via metabolic and non-metabolic pathways.
• Targeting microglial glycolysis presents a promising therapeutic avenue for neuroinflammation.

Conclusions:

• Microglial glycolytic reprogramming is a critical factor in neuroinflammation and neurodegenerative diseases.
• Understanding the glucose-glycolysis-lactate axis in microglia is essential for developing novel therapeutic strategies.
• Targeting microglial metabolism holds potential for treating various central nervous system disorders.