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轴突运输与mRNA在神经退行性疾病中的局部翻译

Axonal Transport and Local Translation of mRNA in Neurodegenerative Diseases.

作者信息

Nagano Seiichi, Araki Toshiyuki

机构信息

Department of Neurotherapeutics, Osaka University Graduate School of Medicine, Osaka, Japan.

Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.

出版信息

Front Mol Neurosci. 2021 Jun 14;14:697973. doi: 10.3389/fnmol.2021.697973. eCollection 2021.

Abstract

Since neurons have long neurites including axons, it is crucial for the axons to transport many intracellular substances such as proteins and mitochondria in order to maintain their morphology and function. In addition, mRNAs have also been shown to be transported within axons. RNA-binding proteins form complexes with mRNAs, and regulate transport of the mRNAs to axons, as well as locally translate them into proteins. Local translation of mRNAs actively occurs during the development and damage of neurons, and plays an important role in axon elongation, regeneration, and synapse formation. In recent years, it has been reported that impaired axonal transport and local translation of mRNAs may be involved in the pathogenesis of some neurodegenerative diseases. In this review, we discuss the significance of mRNA axonal transport and their local translation in amyotrophic lateral sclerosis/frontotemporal dementia, spinal muscular atrophy, Alzheimer's disease, and fragile X syndrome.

摘要

由于神经元具有包括轴突在内的长神经突,轴突运输许多细胞内物质(如蛋白质和线粒体)对于维持其形态和功能至关重要。此外,mRNA也已被证明在轴突内运输。RNA结合蛋白与mRNA形成复合物,并调节mRNA向轴突的运输以及将它们在局部翻译成蛋白质。mRNA的局部翻译在神经元的发育和损伤过程中积极发生,并在轴突伸长、再生和突触形成中起重要作用。近年来,有报道称轴突运输受损和mRNA的局部翻译可能参与某些神经退行性疾病的发病机制。在本综述中,我们讨论了mRNA轴突运输及其在肌萎缩侧索硬化症/额颞叶痴呆、脊髓性肌萎缩症、阿尔茨海默病和脆性X综合征中的局部翻译的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ef/8236635/e390bf5271f4/fnmol-14-697973-g001.jpg

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