中国科学院上海生命科学研究院神经科学研究所神经信号转导研究组的杜婉璐、黄隽波和姚海兰等研究生在王以政研究员的指导下发现，抑制瞬时受体电势通道TRPC6蛋白降解保护缺血性脑损伤。9月1日医学杂志《临床研究》（The Journal of Clinical Investigation）在线发表该工作。文章探讨了保持TRPC6通道活性治疗脑中风的可能性。
TAT-C6肽（包含calpain切割位点）保护大鼠缺血性脑损伤
脑中风是世界范围内具有高致死率和致残率的疾病。中国每年患脑中风的病人数很多。其中缺血性脑中风约占大多数，脑缺血大多是由于脑内主要血管发生病变或阻塞，造成脑组织血供减少或中断所致。受血供中断直接影响的小部分区域，其神经元坏死，很难挽救。而在其周围区域（称为半影区）的细胞，在恢复血供后也会由于兴奋性氨基酸的毒性而逐渐死亡。半影区延迟性的神经元死亡为脑中风治疗提供了可能的机会。
瞬时受体电势C（TRPC）通道蛋白，在细胞膜上构成非选择性阳离子通道。这些通道存在于哺乳动物的各种细胞中，担负着多种生理功能。其中的成员TRPC3和TRPC6对神经元存活具有重要作用。通过大鼠脑中动脉栓塞的缺血模型，作者们发现半影区神经元TRPC6 蛋白被特异性地降解。这一降解是通过NMDA受体的钙离子依赖的中性蛋白水解酶（Calpain）介导的。他们发现了Calpain切割TRPC6蛋白的位点，并依据其氨基酸序列合成了一段短肽。这种短肽可以阻止缺血过程中TRPC6 蛋白的降解，保护了神经细胞。
该项研究提出阻止Calpain降解TRPC6可能成为治疗缺血性脑损伤的新策略，为治疗脑中风提供了新的思路。此项工作是该研究组研究TRPC6与神经元存活又一新的发现。（生物谷Bioon.com）
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Cell：中风的发病机制
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怎样预防中风
Stroke：超重越多中风风险越高
生物谷推荐英文摘要：
J Clin Invest. doi:10.1172/JCI43165.
Inhibition of TRPC6 degradation suppresses ischemic brain damage in rats
Wanlu Du, Junbo Huang, Hailan Yao, Kechun Zhou, Bo Duan and Yizheng Wang
Laboratory of Neural Signal Transduction, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, State Key Laboratory of Neuroscience, The Graduate School, Chinese Academy of Sciences, Shanghai, China.
Brain injury after focal cerebral ischemia, the most common cause of stroke, develops from a series of pathological processes, including excitotoxicity, inflammation, and apoptosis. While NMDA receptors have been implicated in excitotoxicity, attempts to prevent ischemic brain damage by blocking NMDA receptors have been disappointing. Disruption of neuroprotective pathways may be another avenue responsible for ischemic damage, and thus preservation of neuronal survival may be important for prevention of ischemic brain injury. Here, we report that suppression of proteolytic degradation of transient receptor potential canonical 6 (TRPC6) prevented ischemic neuronal cell death in a rat model of stroke. The TRPC6 protein level in neurons was greatly reduced in ischemia via NMDA receptor–dependent calpain proteolysis of the N-terminal domain of TRPC6 at Lys16. This downregulation was specific for TRPC6 and preceded neuronal death. In a rat model of ischemia, activating TRPC6 prevented neuronal death, while blocking TRPC6 increased sensitivity to ischemia. A fusion peptide derived from the calpain cleavage site in TRPC6 inhibited degradation of TRPC6, reduced infarct size, and improved behavioral performance measures via the cAMP response element–binding protein (CREB) signaling pathway. Thus, TRPC6 proteolysis contributed to ischemic neuronal cell death, and suppression of its degradation preserved neuronal survival and prevented ischemic brain damage.
