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长非编码 RNA 在运动神经元发育和疾病中的作用。

Long non-coding RNAs in motor neuron development and disease.

机构信息

Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.

出版信息

J Neurochem. 2021 Mar;156(6):777-801. doi: 10.1111/jnc.15198. Epub 2020 Oct 10.

Abstract

Long non-coding RNAs (lncRNAs) are RNAs that exceed 200 nucleotides in length and that are not translated into proteins. Thousands of lncRNAs have been identified with functions in processes such as transcription and translation regulation, RNA processing, and RNA and protein sponging. LncRNAs show prominent expression in the nervous system and have been implicated in neural development, function and disease. Recent work has begun to report on the expression and roles of lncRNAs in motor neurons (MNs). The cell bodies of MNs are located in cortex, brainstem or spinal cord and their axons project into the brainstem, spinal cord or towards peripheral muscles, thereby controlling important functions such as movement, breathing and swallowing. Degeneration of MNs is a pathological hallmark of diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. LncRNAs influence several aspects of MN development and disruptions in these lncRNA-mediated effects are proposed to contribute to the pathogenic mechanisms underlying MN diseases (MNDs). Accumulating evidence suggests that lncRNAs may comprise valuable therapeutic targets for different MNDs. In this review, we discuss the role of lncRNAs (including circular RNAs [circRNAs]) in the development of MNs, discuss how lncRNAs may contribute to MNDs and provide directions for future research.

摘要

长链非编码 RNA(lncRNA)是指长度超过 200 个核苷酸且不翻译成蛋白质的 RNA。已经鉴定出数千种具有转录和翻译调控、RNA 加工以及 RNA 和蛋白质海绵作用等功能的 lncRNA。lncRNA 在神经系统中表达明显,并与神经发育、功能和疾病有关。最近的工作开始报道 lncRNA 在运动神经元(MNs)中的表达和作用。MNs 的细胞体位于皮质、脑干或脊髓中,其轴突投射到脑干、脊髓或外周肌肉,从而控制运动、呼吸和吞咽等重要功能。MNs 的退化是肌萎缩侧索硬化症和脊髓性肌萎缩症等疾病的病理标志。lncRNA 影响 MN 发育的几个方面,并且这些 lncRNA 介导的作用的中断被提出有助于 MN 疾病(MNDs)的发病机制。越来越多的证据表明,lncRNA 可能成为不同 MND 的有价值的治疗靶点。在这篇综述中,我们讨论了 lncRNA(包括环状 RNA [circRNA])在 MN 发育中的作用,讨论了 lncRNA 如何导致 MND,并为未来的研究提供了方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b0d/8048821/4d3e88365368/JNC-156-777-g002.jpg

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