中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (4): 574-577.doi: 10.4103/1673-5374.248108

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

通过靶向遗传性痉挛性截瘫的线粒体动力学来挽救轴突缺陷

  

  • 出版日期:2019-04-15 发布日期:2019-04-15

Yongchao Mou 1, 2 , Xue-Jun Li 1, 2   

  1. 1 Department of Biomedical Sciences, University of Illinois College of Medicine Rockford, Rockford, IL, USA
    2 Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA
  • Online:2019-04-15 Published:2019-04-15
  • Contact: Xue-Jun Li, PhD, xjli23@uic.edu.
  • Supported by:

    The work was supported by the Blazer Foundation (to XJL).

摘要:

orcid: 0000-0003-1899-9134(Xue-Jun Li)

Abstract:

Impaired axonal development and degeneration underlie debilitating neurodegenerative diseases including hereditary spastic paraplegia, a large group of inherited diseases. Hereditary spastic paraplegia is caused by retrograde degeneration of the long corticospinal tract axons, leading to progressive spasticity and weakness of leg and hip muscles. There are over 70 subtypes with various underlying pathophysiological processes, such as defective vesicular trafficking, lipid metabolism, organelle shaping, axonal transport, and mitochondrial dysfunction. Although hereditary spastic paraplegia consists of various subtypes with different pathological characteristics, defects in mitochondrial morphology and function emerge as one of the common cellular themes in hereditary spastic paraplegia. Mitochondrial morphology and function are remodeled by mitochondrial dynamics regulated by several key fission and fusion mediators. However, the role of mitochondrial dynamics in axonal defects of hereditary spastic paraplegia remains largely unknown. Recently, studies reported perturbed mitochondrial morphology in hereditary spastic paraplegia neurons. Moreover, downregulation of mitochondrial fission regulator dynamin-related protein 1, both pharmacologically and genetically, could rescue axonal outgrowth defects in hereditary spastic paraplegia neurons, providing a potential therapeutic target for treating these hereditary spastic paraplegia. This mini-review will describe the regulation of mitochondrial fission/fusion, the link between mitochondrial dynamics and axonal defects, and the recent progress on the role of mitochondrial dynamics in axonal defects of hereditary spastic paraplegia.

Key words: hereditary spastic paraplegia, axonal degeneration, mitochondrial dynamics, fission, fusion, dynamin-related protein 1, mitochondrial dysfunction, induced pluripotent stem cells