Axonal mRNA translation in neurological disorders.

Axonal mRNA translation in neurological disorders.
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DOI:
10.1080/15476286.2020.1822638
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发表时间:
2021-07
期刊:
影响因子:
4.1
通讯作者:
Holt CE
Holt CE
中科院分区:
生物学3区
文献类型:
--
作者:
Lin JQ;van Tartwijk FW;Holt CE

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人们越来越认识到,局部蛋白合成(LPS)在发育和成熟神经元的轴突生物学的基本方面都起着重要作用。RNA结合蛋白(rbp)的突变,作为LPS的核心参与者,以及其他影响RNA定位和翻译的蛋白质与一系列神经系统疾病有关,这表明LPS的破坏可能具有病理意义。在这篇综述中,我们通过研究LPS与关键轴突过程之间的联系以及LPS失调所涉及的病理生理后果来证实这一假设。首先,我们描述了轴突的长度和自主性如何导致对LPS的特殊依赖。接下来,我们将讨论LPS在维持轴突结构和功能极性以及轴突运输中的作用。然后,我们考虑LPS如何通过调节轴突分支和修剪来促进神经元连接的建立,它如何介导轴突存活到成年期及其参与神经元应激反应。
It is increasingly recognized that local protein synthesis (LPS) contributes to fundamental aspects of axon biology, in both developing and mature neurons. Mutations in RNA-binding proteins (RBPs), as central players in LPS, and other proteins affecting RNA localization and translation are associated with a range of neurological disorders, suggesting disruption of LPS may be of pathological significance. In this review, we substantiate this hypothesis by examining the link between LPS and key axonal processes, and the implicated pathophysiological consequences of dysregulated LPS. First, we describe how the length and autonomy of axons result in an exceptional reliance on LPS. We next discuss the roles of LPS in maintaining axonal structural and functional polarity and axonal trafficking. We then consider how LPS facilitates the establishment of neuronal connectivity through regulation of axonal branching and pruning, how it mediates axonal survival into adulthood and its involvement in neuronal stress responses.
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