Leveraging the ATP-P2X7 receptor signalling axis to alleviate traumatic CNS damage and related complications

The P2X7 receptor is an exceptional member of the P2X purinergic receptor family, with its activation requiring high concentrations of extracellular adenosine 5ʹ-triphosphate (ATP) that are often associated with tissue damage and inflammation. In the central nervous system (CNS), it is highly expressed in glial cells, particularly in microglia. In this review, we discuss the role and mechanisms of the P2X7 receptor in mediating neuroinflammation and other pathogenic events in a variety of traumatic CNS damage conditions, which lead to loss of neurological and cognitive functions. We raise the perspective on the steady progress in developing CNS-penetrant P2X7 receptor-specific antagonists that leverage the ATP-P2X7 receptor signaling axis as a potential therapeutic strategy to alleviate traumatic CNS damage and related complications.