Mitochondrial dynamic abnormalities in amyotrophic lateral sclerosis.

Zhen Jiang,George Perry,Xinglong Wang,Xiongwei Zhu,Wenzhang Wang

doi:10.1186/s40035-015-0037-x

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease characterized by progressive loss of motor neurons in the brainstem and spinal cord. Currently, there is no cure or effective treatment for ALS and the cause of disease is unknown in the majority of ALS cases. Neuronal mitochondria dysfunction is one of the earliest features of ALS. Mitochondria are highly dynamic organelles that undergo continuous fission, fusion, trafficking and turnover, all of which contribute to the maintenance of mitochondrial function. Abnormal mitochondrial dynamics have been repeatedly reported in ALS and increasing evidence suggests altered mitochondrial dynamics as possible pathomechanisms underlying mitochondrial dysfunction in ALS. Here, we provide an overview of mitochondrial dysfunction and dynamic abnormalities observed in ALS, and discuss the possibility of targeting mitochondrial dynamics as a novel therapeutic approach for ALS.

Highlights

Amyotrophic lateral sclerosis (ALS), referred to as Lou Gehrig’s disease, typically develops between 50 and 60 years of age and progresses rapidly with the average survival of less than 30 months after diagnosis or onset [1]
In addition to regulating mitochondrial morphology, mitochondrial fission and fusion are involved in mitochondrial distribution and movement [83,84,85]
SOD1 and TDP43, the most studied proteins associated with ALS, are found involved in the regulation of mitochondrial dynamics

Summary

Introduction

Amyotrophic lateral sclerosis (ALS), referred to as Lou Gehrig’s disease, typically develops between 50 and 60 years of age and progresses rapidly with the average survival of less than 30 months after diagnosis or onset [1]. Many ALS associated mutations in SOD1 result in the loss of antioxidant activity and the overproduction of reactive oxygen species (ROS) [16,17,18,19], and not surprisingly, a large number of studies reported increased oxidative stress or oxidative damage in spinal cords of ALS patients [20,21,22]. Previous studies from multiple groups showed that mitochondria became fragmented in cell and animal models expressing ALS-associated mutant SOD1 [29,30,31,32,33].

Results

Conclusion