P2 receptor-mediated signaling in the physiological and pathological brain: From development to aging and disease

The purinergic pathway mediates both pro-inflammatory and anti-inflammatory responses, whereas the breakdown of adenosine triphosphate (ATP) is in a critical equilibrium. Under physiological conditions, extracellular ATP is maintained at a nanomolar concentration. Whether released into the medium following tissue damage, inflammation, or hypoxia, ATP is considered a clear indicator of cell damage and a marker of pathological conditions. In this overview, we provide an update on the participation of P2 receptor-mediated purinergic signaling in normal and pathological brain development, with special emphasis on neurodevelopmental psychiatric disorders. Since purinergic signaling is ubiquitous, it is not surprising that it plays a prominent role in developmental processes and pathological alterations. The main aim of this review is to conceptualize the time-dependent dynamic changes in the participation of different players in the purinome in shaping the normal and aberrant developmental patterns and diseases of the central nervous system over one's lifespan. © 2023 The Authors