Metabolic determinants of leukocyte pathogenicity in neurological diseases

Neuroinflammatory and neurodegenerative diseases are characterized by the recruitment of circulating blood-borne innate and adaptive immune cells into the central nervous system (CNS). These leukocytes sustain the detrimental response in the CNS by releasing pro-inflammatory mediators that induce activation of local glial cells, blood-brain barrier (BBB) dysfunction, and neural cell death. However, infiltrating peripheral immune cells could also dampen CNS inflammation and support tissue repair. Recent advances in the field of immunometabolism demonstrate the importance of metabolic reprogramming for the activation and functionality of such innate and adaptive immune cell populations. In particular, an increasing body of evidence suggests that the activity of metabolites and metabolic enzymes could influence the pathogenic potential of immune cells during neuroinflammatory and neurodegenerative disorders. In this review, we discuss the role of intracellular metabolic cues in regulating leukocyte-mediated CNS damage in Alzheimer's and Parkinson's disease, multiple sclerosis and stroke, highlighting the therapeutic potential of drugs targeting metabolic pathways for the treatment of neurological diseases.