Xie Yu-Feng, Macdonald John F, Jackson Michael F
Int J Physiol Pathophysiol Pharmacol. 2010 Mar 15;2(2):95-103.
NMDA receptor overactivation triggers intracellular Ca(2+) dysregulation, which has long been thought to be critical for initiating excitotoxic cell death cascades associated with stroke and neurodegenerative disease. The inability of NMDA receptor antagonists to afford neuroprotection in clinical stroke trials has led to a re-evaluation of excitotoxic models of cell death and has focused research efforts towards identifying additional Ca(2+) influx pathways. Recent studies indicate that TRPM2, a member of the TRPM subfamily of Ca(2+)-permeant, non-selective cation channel, plays an important role in mediating cellular responses to a wide range of stimuli that, under certain situations, can induce cell death. These include reactive oxygen and nitrogen species, tumour necrosis factor as well as soluble oli-gomers of amyloid beta. However, the molecular basis of TRPM2 channel involvement in these processes is not fully understood. In this review, we summarize recent studies about the regulation of TRPM2, its interaction with calcium and the possible implications for neurodegenerative diseases.
N-甲基-D-天冬氨酸（NMDA）受体过度激活会引发细胞内钙离子失调，长期以来人们一直认为这对于启动与中风和神经退行性疾病相关的兴奋性毒性细胞死亡级联反应至关重要。NMDA受体拮抗剂在临床中风试验中未能提供神经保护作用，这导致人们重新评估细胞死亡的兴奋性毒性模型，并将研究重点转向识别其他钙离子内流途径。最近的研究表明，瞬时受体电位M型2（TRPM2）是TRPM亚家族中一种钙离子通透的非选择性阳离子通道的成员，在介导细胞对多种刺激的反应中起重要作用，在某些情况下，这些刺激可诱导细胞死亡。这些刺激包括活性氧和氮物种、肿瘤坏死因子以及β淀粉样蛋白的可溶性寡聚体。然而，TRPM2通道参与这些过程的分子基础尚未完全了解。在这篇综述中，我们总结了关于TRPM2调节、其与钙的相互作用以及对神经退行性疾病可能影响的最新研究。
