Immunometabolism In Brain Aging and Neurodegeneration: Bridging Metabolic Pathways and Immune Responses

The complex set of interactions between the immune system and metabolism, known as immunometabolism, has emerged as a critical regulator of disease outcomes in the central nervous system. Numerous studies have linked metabolic disturbances to impaired immune responses in brain aging, neurodegenerative disorders, and brain injury. In this review, we will discuss how disruptions in brain immunometabolism balance contribute to the pathophysiology of brain dysfunction. The first part of the review summarizes the contributions of critical immune cell populations such as microglia, astrocytes, and infiltrating immune cells in mediating inflammation and metabolism in CNS disorders. The remainder of the review addresses the impact of metabolic changes on immune cell activation and disease progression in brain aging, Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, spinal cord injury, and traumatic brain injury. Furthermore, we also address the therapeutic potential of targeting immunometabolic pathways to reduce neuroinflammation and slow disease progression. By focusing on the interactions among brain immune cells and the metabolic mechanisms they recruit in disease, we present a comprehensive overview of brain immunometabolism in human health and disease.