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BAX to basics: How the BCL2 gene family controls the death of retinal ganglion cells
Progress in Retinal and Eye Research ( IF 17.8 ) Pub Date : 2017-01-04 , DOI: 10.1016/j.preteyeres.2017.01.002
Margaret E. Maes , Cassandra L. Schlamp , Robert W. Nickells

Retinal ganglion cell (RGC) death is the principal consequence of injury to the optic nerve. For several decades, we have understood that the RGC death process was executed by apoptosis, suggesting that there may be ways to therapeutically intervene in this cell death program and provide a more direct treatment to the cells and tissues affected in diseases like glaucoma. A major part of this endeavor has been to elucidate the molecular biological pathways active in RGCs from the point of axonal injury to the point of irreversible cell death. A major component of this process is the complex interaction of members of the BCL2 gene family. Three distinct family members of proteins orchestrate the most critical junction in the apoptotic program of RGCs, culminating in the activation of pro-apoptotic BAX. Once active, BAX causes irreparable damage to mitochondria, while precipitating downstream events that finish off a dying ganglion cell. This review is divided into two major parts. First, we summarize the extent of knowledge of how BCL2 gene family proteins interact to facilitate the activation and function of BAX. This area of investigation has rapidly changed over the last few years and has yielded a dramatically different mechanistic understanding of how the intrinsic apoptotic program is run in mammalian cells. Second, we provided a comprehensive analysis of nearly two decades of investigation of the role of BAX in the process of RGC death, much of which has provided many important insights into the overall pathophysiology of diseases like glaucoma.



中文翻译:

BAX基础知识:BCL2基因家族如何控制视网膜神经节细胞的死亡

视网膜神经节细胞(RGC)的死亡是视神经损伤的主要后果。几十年来,我们已经了解到RGC的死亡过程是通过细胞凋亡来执行的,这表明可能存在治疗方法干预该细胞死亡程序,并为受青光眼等疾病影响的细胞和组织提供更直接的治疗方法。这项工作的主要部分是阐明从轴突损伤到不可逆细胞死亡的角度,RGC中活跃的分子生物学途径。此过程的主要组成部分是BCL2成员之间的复杂交互基因家族。蛋白质的三个截然不同的家族成员编配了RGC凋亡程序中最关键的连接点,最终导致了促凋亡BAX的激活。一旦活跃,BAX会对线粒体造成不可挽回的损害,同时会沉淀下游的事件,最终使垂死的神经节细胞消失。这篇评论分为两个主要部分。首先,我们总结一下有关BCL2的知识程度基因家族蛋白相互作用以促进BAX的激活和功能。在过去的几年中,这一研究领域发生了迅速的变化,并且对如何在哺乳动物细胞中运行内在凋亡程序产生了截然不同的机制理解。其次,我们对BAX在RGC死亡过程中的作用进行了近二十年的调查,提供了全面的分析,其中许多研究为青光眼等疾病的整体病理生理学提供了许多重要见解。

更新日期:2017-01-04
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