Mitochondrial dysfunction is a converging point of multiple pathological pathways in amyotrophic lateral sclerosis

Ping Shi, Yanming Wei, Jiayu Zhang, Jozsef Gal, Haining Zhu

Research output: Contribution to journalReview articlepeer-review

77 Scopus citations


A better understanding of the etiology of amyotrophic lateral sclerosis (ALS) is needed to develop effective therapies for the treatment of this fatal neurodegenerative disease. Extensive studies have produced a general agreement that ALS is likely to be a multifactorial and multisystem disease. Many mechanisms have been postulated to be involved in the pathology of ALS, such as oxidative stress, glutamate excitotoxicity, mitochondrial damage, defective axonal transport, glia cell pathology, and aberrant RNA metabolism. Mitochondria have shown to be an early target in ALS pathogenesis and contribute to the disease progression. Morphological and functional defects in mitochondria were found in both human patients and ALS mice overexpressing mutant SOD1. Mutant SOD1 was found to be preferentially associated with mitochondria and subsequently impair mitochondrial function. Recent studies suggest that axonal transport of mitochondria along microtubules is disrupted in ALS. Furthermore, new evidence suggests that mitochondrial fission and fusion as well as mitophagy clearance may also be affected by mutant SOD1. These results also illustrate the critical importance of maintaining proper mitochondrial function in axons and neuromuscular junctions, supporting the emerging "dying-back" axonopathy model of ALS. In this review, we will discuss findings supporting that mitochondrial dysfunction is likely to be a converging point of multiple pathways underlying the ALS pathogenesis and progression.

Original languageEnglish (US)
Pages (from-to)S311-S324
JournalJournal of Alzheimer's Disease
Issue numberSUPPL.2
StatePublished - 2010
Externally publishedYes


  • Amyotrophic lateral sclerosis
  • autophagy
  • axonal transport
  • mitochondrial dynamics
  • mitochondrial function
  • mutant SOD1

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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