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脑病理学中的翻译调控:生物学意义与治疗机遇。

Translational control in brain pathologies: biological significance and therapeutic opportunities.

机构信息

Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.

出版信息

Acta Neuropathol. 2019 Apr;137(4):535-555. doi: 10.1007/s00401-019-01971-8. Epub 2019 Feb 9.

Abstract

Messenger RNA (mRNA) translation is the terminal step in protein synthesis, providing a crucial regulatory checkpoint for this process. Translational control allows specific cell types to respond to rapid changes in the microenvironment or to serve specific functions. For example, neurons use mRNA transport to achieve local protein synthesis at significant distances from the nucleus, the site of RNA transcription. Altered expression or functions of the various components of the translational machinery have been linked to several pathologies in the central nervous system. In this review, we provide a brief overview of the basic principles of mRNA translation, and discuss alterations of this process relevant to CNS disease conditions, with a focus on brain tumors and chronic neurological conditions. Finally, synthesizing this knowledge, we discuss the opportunities to exploit the biology of altered mRNA translation for novel therapies in brain disorders, as well as how studying these alterations can shed new light on disease mechanisms.

摘要

信使 RNA(mRNA)翻译是蛋白质合成的终末步骤,为该过程提供了一个关键的调节检查点。翻译控制允许特定的细胞类型对微环境中的快速变化做出反应,或者发挥特定的功能。例如,神经元利用 mRNA 运输在远离细胞核(RNA 转录的部位)的地方实现局部蛋白质合成。翻译机制的各种成分的表达或功能的改变与中枢神经系统中的几种病理学有关。在这篇综述中,我们简要概述了 mRNA 翻译的基本原理,并讨论了与中枢神经系统疾病状况相关的该过程的改变,重点是脑肿瘤和慢性神经疾病。最后,综合这些知识,我们讨论了利用改变的 mRNA 翻译的生物学为脑疾病的新疗法提供机会的情况,以及研究这些改变如何为疾病机制提供新的见解。

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