中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (7): 1052-1061.

• 综述:退行性病与再生 • 上一篇    下一篇

肌萎缩性侧索硬化的线粒体质量控制

  

  • 收稿日期:2017-06-27 出版日期:2017-07-15 发布日期:2017-07-15

Mitochondrial quality control in amyotrophic lateral sclerosis: towards a common pathway?

Bilal Khalil1, Jean-Charles Liévens2   

  1. 1 Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA; 2 MMDN, Université de Montpellier, EPHE, INSERM, U1198, Montpellier, France
  • Received:2017-06-27 Online:2017-07-15 Published:2017-07-15
  • Contact: Bilal Khalil, Ph.D. or Jean-Charles Liévens, Ph.D., Khalil.Bilal@mayo.edu or jean-charles.lievens@ umontpellier.fr.

摘要:

肌萎缩性侧索硬化(ALS)是以上、下位运动神经元丧失为特征的破坏性神经退行性疾病。加剧疾病发病和进展的机制有多种,其中线粒体功能障碍是ALS发病机制中的决定因素。实际上,线粒体缺陷主要在ALS相关的SOD1突变体中出现,现在已经确定线粒体在其他ALS条件下也有功能障碍。在这种情况下,线粒体质量控制系统可通过消除和替换受损的线粒体成分或通过线虫病降解整个细胞器,来恢复线粒体的正常功能,并防止细胞死亡。最近的证据表明,ALS相关基因干扰线粒体质量控制系统。文章认为无效的线粒体质量控制可能会使运动神经元无对抗ALS线粒体损伤的能力。

ORCID:0000-0002-0139-2291(Jean-Charles Liévens); 0000-0001-7251-4340(Bilal Khalil)

Abstract:

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by loss of upper and lower motor neurons. Different mechanisms contribute to the disease initiation and progression, including mitochondrial dysfunction which has been proposed to be a central determinant in ALS pathogenesis. Indeed, while mitochondrial defects have been mainly described in ALS-linked SOD1 mutants, it is now well established that mitochondria become also dysfunctional in other ALS conditions. In such context, the mitochondrial quality control system allows to restore normal functioning of mitochondria and to prevent cell death, by both eliminating and replacing damaged mitochondrial components or by degrading the entire organelle through mitophagy. Recent evidence shows that ALS-related genes interfere with the mitochondrial quality control system. This review highlights how ineffective mitochondrial quality control may render motor neurons defenseless towards the accumulating mitochondrial damage in ALS.

Key words: C9orf72, FUS, SOD1, Optineurin, Parkin, PGC-1α, PINK1, TDP-43 proteinopathies, TBK1, VCP