The Multifaceted Role of P2X7R in Microglia and Astrocytes

The purinergic P2X7 receptor (P2X7R) is a unique ATP-gated ion channel that requires unusually high concentrations of extracellular ATP (eATP) for activation, making it a sensor of cellular stress and injury in the central nervous system. This review provides a comprehensive overview of P2X7R expression and function in glial cells, with a particular focus on microglia and astrocytes. We first outline the molecular characteristics of P2X7R and its distribution in brain cell types. In microglia, P2X7R regulates a broad spectrum of processes, including phagocytosis, autophagy, proliferation, and ultimately cell death, underscoring its dual role in neuroprotection and neurotoxicity. In astrocytes, P2X7R contributes to gliotransmission and inflammatory signaling, influencing neuronal excitability and synaptic function. We further explore the role of P2X7R in the context of both Alzheimer’s disease and epilepsy, where a dysregulated eATP-P2X7R signaling axis exacerbates neuroinflammation and glial dysfunction. Understanding the cell-specific roles of P2X7R in physiology and pathology provides new insights into glial biology and highlights its potential as a therapeutic target in brain diseases.