Bedetta Martina, Pizzo Paola, Lia Annamaria
Department of Biomedical Sciences, University of Padova, Padua, Italy.
Neuroscience Institute, Italian National Research Council (CNR), Padua, Italy.
Neurochem Res. 2025 Jul 21;50(4):239. doi: 10.1007/s11064-025-04502-y.
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.
嘌呤能P2X7受体（P2X7R）是一种独特的ATP门控离子通道，需要异常高浓度的细胞外ATP（eATP）才能激活，使其成为中枢神经系统中细胞应激和损伤的传感器。本综述全面概述了P2X7R在胶质细胞中的表达和功能，尤其关注小胶质细胞和星形胶质细胞。我们首先概述P2X7R的分子特征及其在脑细胞类型中的分布。在小胶质细胞中，P2X7R调节广泛的过程，包括吞噬作用、自噬、增殖以及最终的细胞死亡，突显了其在神经保护和神经毒性中的双重作用。在星形胶质细胞中，P2X7R参与胶质递质传递和炎症信号传导，影响神经元兴奋性和突触功能。我们进一步探讨P2X7R在阿尔茨海默病和癫痫背景下的作用，其中失调的eATP - P2X7R信号轴会加剧神经炎症和胶质细胞功能障碍。了解P2X7R在生理和病理过程中的细胞特异性作用，为胶质生物学提供了新的见解，并突出了其作为脑部疾病治疗靶点的潜力。
