Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia
Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia
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DOI：
10.1007/s11064-004-6869-x
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发表时间：
2004-11-01
影响因子：
4.4
通讯作者：
Chan, PH
中科院分区：
文献类型：
--
作者：
Chan, PH
细胞凋亡途径与急性脑损伤（包括脑缺血、脑外伤和脊髓损伤）以及慢性神经退行性疾病有关。实验性缺血和再灌注模型，例如啮齿动物的短暂性局灶性/整体性缺血，已被彻底研究，并表明线粒体和细胞生存/死亡信号通路参与细胞死亡/生存级联。最近的研究表明，线粒体依赖性细胞凋亡涉及促凋亡蛋白和抗凋亡蛋白的结合、细胞色素 c 和第二种线粒体衍生的 caspase 激活剂的释放、下游 caspase-9 和 -3 的激活以及 DNA 片段化。众所周知，在缺血后再灌注过程中，功能失调的线粒体中的线粒体电子传递链中会显着产生活性氧，并且还参与涉及磷脂酰肌醇-3-激酶 (PI3-K)、Akt 和下游信号分子（如 Bad、14-3-3 和富含脯氨酸）的生存信号通路。 Akt 底物 (PRAS) 及其结合。对这些生存途径的进一步研究可能为临床卒中提供新的治疗策略。
Apoptotic cell death pathways have been implicated in acute brain injuries, including cerebral ischemia, brain trauma, and spinal cord injury, and in chronic neurodegenerative diseases. Experimental ischemia and reperfusion models, such as transient focal/global ischemia in rodents, have been thoroughly studied and suggest the involvement of mitochondria and the cell survival/death signaling pathways in cell death/survival cascades. Recent studies have implicated mitochondria-dependent apoptosis involving pro- and antiapoptotic protein binding, the release of cytochrome c and second mitochondria-derived activator of caspase, the activation of downstream caspases-9 and -3, and DNA fragmentation. Reactive oxygen species are known to be significantly generated in the mitochondrial electron transport chain in the dysfunctional mitochondria during reperfusion after ischemia, and are also implicated in the survival signaling pathway that involves phosphatidylinositol-3-kinase (PI3-K), Akt, and downstream signaling molecules, like Bad, 14-3-3, and the proline-rich Akt substrate (PRAS), and their bindings. Further studies of these survival pathways may provide novel therapeutic strategies for clinical stroke.