Advances in treating amyotrophic lateral sclerosis: insights from pathophysiological studies

Trends Neurosci. 2014 Aug;37(8):433-42. doi: 10.1016/j.tins.2014.05.006. Epub 2014 Jun 11.


Amyotrophic lateral sclerosis (ALS) is the most frequently occurring of the neuromuscular degenerative disorders, with a median survival time of 3-5 years. The pathophysiological mechanisms underlying ALS are multifactorial, with a complex interaction between genetic factors and molecular pathways. To date 16 genes and loci have been associated with ALS, with mutations in DNA/RNA-regulating genes including the recently described c9orf72 (chromosome 9 open reading frame 72) gene, suggesting an important role for dysregulation of RNA metabolism in ALS pathogenesis. Further, dysfunction of molecular pathways, including glutamate-mediated excitotoxicity, has been identified in sporadic and familial ALS, indicating the existence of a common pathogenic pathway. These pathophysiological insights have suggested novel therapeutic approaches, including stem cell and genetics-based strategies, providing hope for feasible treatment of ALS.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / pathology
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Amyotrophic Lateral Sclerosis / therapy*
  • C9orf72 Protein
  • Causality
  • DNA-Binding Proteins / genetics
  • Humans
  • Neuroprotective Agents / therapeutic use
  • Proteins / genetics


  • C9orf72 Protein
  • C9orf72 protein, human
  • DNA-Binding Proteins
  • Neuroprotective Agents
  • Proteins