P2Y receptors in microglia and neuroinflammation

Microglia are surveillants in the central nervous system. Once they find abnormal or emergency signals, microglia can migrate to the site of the injury, release pro-inflammatory and/or neurotrophic substances, and phagocytose damaged cells and their remnants. Extracellular nucleotides act through purinoceptors and have been implicated as signaling molecules used by microglia to sense adverse physiological conditions. The P2Y₁₂ receptor is responsible for microglial chemotactic function toward an ATP source. The P2Y₆ receptor stimulates phagocytic activity of microglia in response to extracellular UDP. Each receptor elicits transient intracellular calcium elevation and this may induce the expression of several genes related to microglial activation. Both receptor-mediated signaling and cellular functions may be involved in the pathology occurring in the central nervous system. Therefore, determining the definitive microglial functions mediated by P2Y receptors supports understanding the pathological cascade and finding new therapeutic targets related to microglia.