Prevention of mutant SOD1 motoneuron degeneration by copper chelators in vitro

J Neurobiol. 2000 Jan;42(1):49-55. doi: 10.1002/(sici)1097-4695(200001)42:1<49::aid-neu5>;2-7.


An animal model of familial amyotrophic lateral sclerosis (FALS) has been generated by overexpression of human CuZn superoxide dismutase (SOD1) containing a substitution of glycine to alanine at position 93 in transgenic G93A mice. The loss of motoneurons shown in this model has been attributed to a dominant gain of function of this mutated enzyme, which might be due to copper toxicity. This hypothesis was tested in purified spinal motoneurons cultures originating from G93A transgenic embryos. Spinal motoneurons were isolated from E13 embryos by several steps including density gradient centrifugation. The effect of copper chelators on survival and neurite growth of motoneurons was investigated. Survival of G93A motoneurons was decreased by 46% as compared to wild-type motoneurons. Moreover, G93A motoneurons showed reduced neurite outgrowth. Copper chelators strikingly increased viability of G93A motoneurons (by over 200%) but had no effect on wild-type cells. Presence of DDC in the medium increases the length of neurites from G93A motoneurons. The present results suggest the capacity of copper chelators to reduce the effect of reverse function of mutated SOD1 on motoneurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / enzymology
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / prevention & control
  • Animals
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Cells, Cultured
  • Chelating Agents / pharmacology*
  • Ditiocarb / pharmacology*
  • Mice
  • Mice, Transgenic
  • Motor Neurons / drug effects*
  • Motor Neurons / physiology
  • Neurites / drug effects*
  • Neurites / physiology
  • Spinal Cord / drug effects
  • Spinal Cord / physiology
  • Superoxide Dismutase / genetics*


  • Brain-Derived Neurotrophic Factor
  • Chelating Agents
  • Ditiocarb
  • Superoxide Dismutase