Department of Neurology.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2021 Apr 25;50(2):267-276. doi: 10.3724/zdxbyxb-2021-0110.
Transient receptor potential M2 (TRPM2) ion channel is a non-selective cationic channel that can permeate calcium ions, and plays an important role in neuroinflammation, ischemic reperfusion brain injury, neurodegenerative disease, neuropathic pain, epilepsy and other neurological diseases. In ischemic reperfusion brain injury, TRPM2 mediates neuronal death by modulating the different subunits of glutamate N-methyl-D-aspartic acid receptor in response to calcium/zinc signal. In Alzheimer's disease, TRPM2 is activated by reactive oxygen species generated by β-amyloid peptide to form a malignant positive feedback loop that induces neuronal death and is involved in the pathological process of glial cells by promoting inflammatory response and oxidative stress. In epilepsy, the TRPM2-knockout alleviates epilepsy induced neuronal degeneration by inhibiting autophagy and apoptosis related proteins. The roles of TRPM2 channel in the pathogenesis of various central nervous system diseases and its potential drug development and clinical application prospects are summarized in this review.
瞬时受体电位 M2 (TRPM2) 离子通道是非选择性阳离子通道，可通透钙离子，在神经炎症、缺血再灌注脑损伤、神经退行性疾病、神经性疼痛、癫痫等神经系统疾病中发挥重要作用。在缺血再灌注脑损伤中，TRPM2 通过调节谷氨酸 N-甲基-D-天冬氨酸受体的不同亚基对钙/锌信号做出反应，介导神经元死亡。在阿尔茨海默病中，TRPM2 被β-淀粉样肽产生的活性氧激活，形成一个恶性正反馈回路，通过促进炎症反应和氧化应激诱导神经元死亡，并通过促进炎症反应和氧化应激参与胶质细胞的病理过程。在癫痫中，TRPM2 敲除通过抑制自噬和凋亡相关蛋白来减轻癫痫诱导的神经元退化。本文综述了 TRPM2 通道在各种中枢神经系统疾病发病机制中的作用及其潜在的药物研发和临床应用前景。
