An antiapoptotic neuroprotective role for neuroglobin.
An antiapoptotic neuroprotective role for neuroglobin.
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DOI：
10.3390/ijms11062306
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发表时间：
2010-05-27
影响因子：
5.6
通讯作者：
Birch N
中科院分区：
文献类型：
--
作者：
Brittain T;Skommer J;Raychaudhuri S;Birch N
与线粒体功能障碍相关的细胞死亡在急性神经系统疾病和神经退行性疾病中很常见。神经元凋亡受多种蛋白调节，包括神经红蛋白，一种古老起源的小血红素蛋白。在一些神经元中发现了高浓度的脑红蛋白，并且其高表达已经显示出在体外促进神经元的存活并且在体内保护脑免受中风和阿尔茨海默病的损伤。早期的研究表明，这种保护作用可能源于蛋白质结合氧气或与一氧化氮反应的能力。然而，最近的数据表明，这两种功能都不太可能具有生理意义。其他研究表明，在细胞死亡过程中，脑红蛋白与线粒体释放的细胞色素c反应非常迅速，从而干扰细胞凋亡的内在途径。系统水平的计算模型表明，脑红蛋白的生理作用是重置触发水平后线粒体执行细胞凋亡。因此，了解脑红蛋白的作用机制可能为设计抑制过度神经元细胞死亡的新药物靶点提供合理的基础。
Cell death associated with mitochondrial dysfunction is common in acute neurological disorders and in neurodegenerative diseases. Neuronal apoptosis is regulated by multiple proteins, including neuroglobin, a small heme protein of ancient origin. Neuroglobin is found in high concentration in some neurons, and its high expression has been shown to promote survival of neurons in vitro and to protect brain from damage by both stroke and Alzheimer’s disease in vivo. Early studies suggested this protective role might arise from the protein’s capacity to bind oxygen or react with nitric oxide. Recent data, however, suggests that neither of these functions is likely to be of physiological significance. Other studies have shown that neuroglobin reacts very rapidly with cytochrome c released from mitochondria during cell death, thus interfering with the intrinsic pathway of apoptosis. Systems level computational modelling suggests that the physiological role of neuroglobin is to reset the trigger level for the post-mitochondrial execution of apoptosis. An understanding of the mechanism of action of neuroglobin might thus provide a rational basis for the design of new drug targets for inhibiting excessive neuronal cell death.
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