TRPM7 and ischemic CNS injury
TRPM7 and ischemic CNS injury
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DOI：
10.1177/1073858404272966
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发表时间：
2005-04-01
期刊：
影响因子：
5.6
通讯作者：
Tymianski, M
中科院分区：
文献类型：
--
作者：
Aarts, MM;Tymianski, M
缺血性脑损伤是西方社会发病率和死亡率的主要来源，并对卫生保健系统造成重大的经济负担。迄今为止，很少有有效的治疗方法已经实现治疗中风和曾经有希望的途径，如抗兴奋性毒性治疗与NMDA受体拮抗剂尚未证明临床上有用。因此，我们需要确定新的研究和治疗干预中风引起的神经退行性变的目标。瞬时受体电位（TRP）通道是一个激动人心的新的阳离子通道家族，对细胞内和细胞外刺激都有反应。事实上，几个成员可以通过氧化应激和氧自由基诱导。我们最近已经证明，TRPM7是一个重要的介导缺氧神经元死亡的氧化应激激活，在平行的兴奋性毒性信号通路。因此，缺血性脑损伤的未来治疗可能需要包括抑制或调节TRPM7活性的策略。需要进一步研究TRPM7和其他TRIP家族成员的生理学和病理生理学，以提供药理学靶点并更好地了解缺血性脑疾病。
Ischemic brain damage represents a major source of morbidity and mortality in westernized society and poses a significant financial burden on the health care system. To date, few effective therapies have been realized to treat stroke and once promising avenues such as antiexcitotoxic therapy with NMDA receptor antagonists have not proven clinically useful. Thus, we need to identify new targets for research and therapeutic intervention of the neurodegeneration caused by stroke. Transient receptor potential (TRP) channels are an exciting new family of cation channels that respond to intracellular and extracellular stimuli. Indeed, several members can be induced by oxidative stress and oxygen free radicals. We have recently demonstrated that one member, TRPM7, is an essential mediator of anoxic neuronal death that is activated by oxidative stress, in parallel to excitotoxic signal pathways. Thus, future treatment of ischemic brain injury may need to include strategies that inhibit or modulate TRPM7 activity. Further investigation of the physiology and pathophysiology of TRPM7 and other TRIP family members is needed to provide both pharmacological targets and a better understanding of ischemic brain disorders.