Establishing a novel C. elegans model to investigate the role of autophagy in amyotrophic lateral sclerosis

Acta Pharmacol Sin. 2013 May;34(5):644-50. doi: 10.1038/aps.2012.190. Epub 2013 Mar 18.


Aim: To develop a C. elegans model of amyotrophic lateral sclerosis (ALS) and to evaluate the role of autophagy in the disease.

Methods: Stable transgenic worms expressing the G93A mutant form of Cu,Zn-superoxide dismutase (SOD1) in GABAergic motor neurons were generated. Axon guidance and protein aggregation in the motor neurons were observed with fluorescence microscopy. A paralysis assay was performed to evaluate the motor function of the transgenic worms. The expression of autophagic genes in daf-2(e1370) mutants was analyzed using real-time PCR. The reporter GFP::LGG-1 was used to verify whether autophagy was induced in motor neurons.

Results: Expression of G93A SOD1 in motor neurons caused age-dependent motor defects accompanied by significant SOD1 aggregation and axon guidance failure. After 12 d, over 80% of the G93A worms became paralyzed, whereas less than 10% of the controls showed a paralytic phenotype. In the daf-2(e1370) mutants of C. elegans, the levels of autophagic genes bec-1, atg-7, lgg-1, and atg-18 were upregulated by approximately 1.5-fold, the level of unc-51 increased by approximately fourfold, and autophagosomes in motor neurons was markedly increased. Crossing the daf-2(e1370) mutation into the G93A SOD1 mutant worms significantly ameliorated the motor defects, SOD1 aggregation, and axon guidance failure.

Conclusion: G93A SOD1 expression in motor neurons of C. elegans results in characteristic alterations of ALS. Increased autophagy protects C. elegans motor neurons against the toxicity of mutant SOD1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / pathology
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Animals
  • Animals, Genetically Modified
  • Autophagy*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Disease Models, Animal*
  • Humans
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Paralysis / genetics
  • Paralysis / pathology
  • Paralysis / physiopathology
  • Point Mutation
  • Receptor, Insulin / genetics
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase-1


  • Caenorhabditis elegans Proteins
  • SOD1 protein, human
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • DAF-2 protein, C elegans
  • Receptor, Insulin