Absence of tumor necrosis factor-alpha does not affect motor neuron disease caused by superoxide dismutase 1 mutations

J Neurosci. 2006 Nov 1;26(44):11397-402. doi: 10.1523/JNEUROSCI.0602-06.2006.


An increase in the expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) has been observed in patients with amyotrophic lateral sclerosis (ALS) and in the mice models of the disease. TNF-alpha is a potent activator of macrophages and microglia and, under certain conditions, can induce or exacerbate neuronal cell death. Here, we assessed the contribution of TNF-alpha in motor neuron disease in mice overexpressing mutant superoxide dismutase 1 (SOD1) genes linked to familial ALS. This was accomplished by the generation of mice expressing SOD1(G37R) or SOD1(G93A) mutants in the context of TNF-alpha gene knock out. Surprisingly, the absence of TNF-alpha did not affect the lifespan or the extent of motor neuron loss in SOD1 transgenic mice. These results provide compelling evidence indicating that TNF-alpha does not directly contribute to motor neuron degeneration caused by SOD1 mutations.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Motor Neuron Disease / enzymology
  • Motor Neuron Disease / genetics*
  • Motor Neuron Disease / pathology
  • Mutation*
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Tumor Necrosis Factor-alpha / deficiency
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / physiology


  • Tumor Necrosis Factor-alpha
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1