Nuclear transport, oxidative stress, and neurodegeneration.
Nuclear transport, oxidative stress, and neurodegeneration.
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DOI：
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发表时间：
2011-02
影响因子：
1.4
通讯作者：
V. Patel;C. Chu
中科院分区：
文献类型：
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作者：
V. Patel;C. Chu
转录因子在细胞质和细胞核之间的运输是信号转导的一个重要方面，由于神经元的高度极化结构，这在神经元中特别具有挑战性。在人类神经退行性疾病的受影响神经元中观察到许多蛋白质（包括转录因子）的亚细胞定位的破坏。在这些疾病中，也有越来越多的证据支持核转运的改变作为所观察到的蛋白质错误定位的潜在机制。在这些疾病中起关键致病作用的氧化应激也与核转运的显著改变相关。在概述了主要的核输入和输出途径，并讨论了氧化损伤对核蛋白质运输的影响后，本文综述了核转运改变作为神经退行性疾病发病机制的新证据。还讨论了克服这种缺陷的潜在战略。
Trafficking of transcription factors between the cytoplasm and the nucleus is an essential aspect of signal transduction, which is particularly challenging in neurons due to their highly polarized structure. Disruption in the subcellular localization of many proteins, including transcription factors, is observed in affected neurons of human neurodegenerative diseases. In these diseases, there is also growing evidence supporting alterations in nuclear transport as potential mechanisms underlying the observed mislocalization of proteins. Oxidative stress, which plays a key pathogenic role in these diseases, has also been associated with significant alterations in nuclear transport. After providing an overview of the major nuclear import and export pathways and discussing the impact of oxidative injury on nuclear trafficking of proteins, this review synthesizes emerging evidence for altered nuclear transport as a possible mechanism in the pathogenesis of neurodegenerative diseases. Potential strategies to overcome such deficits are also discussed.