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

作　　者：Bilal Khalil Jean-Charles Liévens 

机构地区：[1]Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA [2]MMDN,Université de Montpellier, EPHE, INSERM, U1198, Montpellier, France

出　　处：《Neural Regeneration Research》2017年第7期1052-1061,共10页中国神经再生研究（英文版）

摘　　要：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.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.

关 键 词：C9orf72 FUS SOD1 OPTINEURIN PARKIN PGC-1α PINK1 TDP-43 proteinopathies TBK1 VCP 

分 类 号：R744.8[医药卫生—神经病学与精神病学]