Zhao Ya-Fei, Tang Yong, Illes Peter
School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
International Collaborative Center on Big Science Plan for Purine Signaling, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Mol Neurosci. 2021 Feb 9;14:641570. doi: 10.3389/fnmol.2021.641570. eCollection 2021.
P2X7 receptors are members of the ATP-gated cationic channel family with a preferential localization at the microglial cells, the resident macrophages of the brain. However, these receptors are also present at neuroglia (astrocytes, oligodendrocytes) although at a considerably lower density. They mediate necrosis/apoptosis by the release of pro-inflammatory cytokines/chemokines, reactive oxygen species (ROS) as well as the excitotoxic (glio)transmitters glutamate and ATP. Besides mediating cell damage i.e., superimposed upon chronic neurodegenerative processes in Alzheimer's Disease, Parkinson's Disease, multiple sclerosis, and amyotrophic lateral sclerosis, they may also participate in neuroglial signaling to neurons under conditions of high ATP concentrations during any other form of neuroinflammation/neurodegeneration. It is a pertinent open question whether P2X7Rs are localized on neurons, or whether only neuroglia/microglia possess this receptor-type causing indirect effects by releasing the above-mentioned signaling molecules. We suggest as based on molecular biology and functional evidence that neurons are devoid of P2X7Rs although the existence of neuronal P2X7Rs cannot be excluded with absolute certainty.
P2X7受体是ATP门控阳离子通道家族的成员，主要定位于小胶质细胞，即脑内的常驻巨噬细胞。然而，这些受体在神经胶质细胞（星形胶质细胞、少突胶质细胞）中也有表达，不过密度要低得多。它们通过释放促炎细胞因子/趋化因子、活性氧（ROS）以及兴奋性毒性（神经胶质）递质谷氨酸和ATP来介导坏死/凋亡。除了介导细胞损伤，即在阿尔茨海默病、帕金森病、多发性硬化症和肌萎缩侧索硬化症等慢性神经退行性疾病过程中叠加的损伤外，它们还可能在任何其他形式的神经炎症/神经退行性变过程中，在高ATP浓度条件下参与神经胶质细胞向神经元的信号传递。P2X7受体是否定位于神经元，或者是否只有神经胶质细胞/小胶质细胞拥有这种受体类型并通过释放上述信号分子产生间接影响，这是一个相关的开放性问题。基于分子生物学和功能证据，我们认为神经元缺乏P2X7受体，尽管不能绝对排除神经元P2X7受体的存在。
