中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (10): 1950-1957.doi: 10.4103/1673-5374.308074

• 综述:退行性病与再生 • 上一篇    下一篇

神经退行性疾病中神经元轴突mRNA的定位和局部翻译

  

  • 出版日期:2021-10-15 发布日期:2021-03-18

Axonal mRNA localization and local translation in neurodegenerative disease

Jin-Xin Lu1, #, Yang Wang1, 2, #, Yi-Jie Zhang1, #, Mei-Fen Shen1, Hai-Ying Li1, *, Zheng-Quan Yu1, *, Gang Chen1#br#   

  1. 1Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China; 2Department of Neurosurgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui Province, China
  • Online:2021-10-15 Published:2021-03-18
  • Contact: Haiying Li, MD, lhy1015@suda.edu.cn; Zhengquan Yu, MD, ahsz_neurosurgery@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81830036 (to GC), 81771255 (to GC), 81771254 (to HYL), 81971106 (to ZQY); Project of Jiangsu Provincial Medical Innovation Team, No. CXTDA2017003 (to GC); Jiangsu Provincial Medical Youth Talent, No. QNRC2016728 (to HYL); the Natural Science Foundation of Jiangsu Province, No. BK20170363 (to HYL); Gusu Health Personnel Training Project, No. GSWS2019030 (to HYL).

摘要:

Neural Regen Res轴突mRNA定位和局部翻译异常在神经退行性疾病中起重要作用

神经元结构复杂、高度分化, 轴突、树突由于距离胞核较远,需要特定的信息传递处理形式应对局部信号刺激,其中很重要的一步就是mRNA转运至轴突并进行局部翻译。mRNA在特定亚细胞区里的定位非常普遍,这可以使基因在细胞质内由于空间限制产生特定性的表达,可以根据局部信号刺激调节局部翻译,并且对局部翻译产生的蛋白进行保护。在哺乳动物神经元中局部翻译主要有两个作用:(1)为细胞提供了应对环境信号的手段,在发育过程中发挥轴突延伸和寻路的功能,以及在成熟细胞中实现突触功能和维持功能;(2)通过表达转录因子和核质转运因子,调节细胞核中的转录,从而使细胞对损伤做出反应并与细胞体进行通讯。

神经退行性疾病包括阿尔茨海默病(AD)、帕金森病(PD)、额颞叶痴呆(FTD)、肌萎缩性侧索硬化症(ALS)、亨廷顿病(HD)等。这些疾病表现出一系列类似的症状和体征,包括认知障碍、步态不稳定、虚弱、情绪失衡以及精神疾病症状。内源性蛋白聚集成错误折叠的不溶性包埋体是这些疾病最显著的共同特征之一。有很多研究表明轴突的局部翻译存在于发育中的轴突和对神经损伤做出反应的轴突中。在这些神经退行性疾病中,轴突mRNA的运输、定位和局部翻译均可能出现异常变化。并且在不同的疾病中,同一种蛋白或mRNA可能会多次出现,表现出完全不同的功能,并形成一个相互作用的网络。

 

文章在《中国神经再生研究(英文版)》杂志2021年10月10期发表。

https://orcid.org/0000-0003-4301-8000 (Haiying Li)

Abstract: The regulation of mRNA localization and local translation play vital roles in the maintenance of cellular structure and function. Many human neurodegenerative diseases, such as fragile X syndrome, amyotrophic lateral sclerosis, Alzheimer’s disease, and spinal muscular atrophy, have been characterized by pathological changes in neuronal axons, including abnormal mRNA translation, the loss of protein expression, or abnormal axon transport. Moreover, the same protein and mRNA molecules have been associated with variable functions in different diseases due to differences in their interaction networks. In this review, we briefly examine fragile X syndrome, amyotrophic lateral sclerosis, Alzheimer’s disease, and spinal muscular atrophy, with a focus on disease pathogenesis with regard to local mRNA translation and axon transport, suggesting possible treatment directions.

Key words: Alzheimer’s disease, amyotrophic lateral sclerosis, axonal transport, fragile X syndrome, local translation, mRNA localization, neuron, spinal muscular atrophy