Future targets and cascades for neuroprotective strategies
Future targets and cascades for neuroprotective strategies
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DOI：
10.1161/01.str.0000143325.25610.ac
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发表时间：
2004-11-01
期刊：
影响因子：
8.3
通讯作者：
Chan, PH
中科院分区：
文献类型：
--
作者：
Chan, PH
大量的证据表明，在各种实验动物模型中，细胞凋亡在脑缺血后神经元死亡中起着关键作用。脑血流中断后导致凋亡性细胞死亡的时间依赖性分子和生化后遗症已经确立。许多靶向细胞死亡途径的神经保护剂已经失败，需要考虑替代策略。一种这样的策略是靶向神经元存活信号传导途径，其涉及磷脂酰肌醇3-激酶（PI 3-K）/Akt（蛋白激酶B）途径。已经证明，PI 3-K/Akt和下游磷酸化Bad和富含脯氨酸的Akt底物存活信号级联在过表达铜锌超氧化物歧化酶活性的缺血脑中的存活神经元中上调。这些研究为脑卒中神经保护策略中的新治疗靶点提供了动力。
Cumulative evidence suggests that apoptosis plays a pivotal role in neuronal death after cerebral ischemia in various experimental animal models. The time-dependent molecular and biochemical sequelae that lead to apoptotic cell death after the interruption of cerebral blood flow have been established. Many neuroprotective agents that target cell death pathways have been failures, and alternative strategies need to be considered. One such strategy is to target the neuronal survival signaling pathway, which involves the phosphatidylinositol 3-kinase (PI3-K)/Akt (protein kinase B) pathway. It has been demonstrated that PI3-K/Akt and downstream phosphorylated Bad and proline-rich Akt substrate survival signaling cascades are upregulated in surviving neurons in the ischemic brain that overexpresses copper-zinc superoxide dismutase activity. These studies provide an impetus for novel therapeutic targets in neuroprotective strategies in stroke.