Inflammatory cytokines increase mitochondrial damage in motoneuronal cells expressing mutant SOD1

Alberto Ferri, Monica Nencini, Mauro Cozzolino, Paolo Carrara, Sandra Moreno, Maria Teresa Carrì

Research output: Contribution to journalArticlepeer-review


Recent studies indicate that molecular signals from microglia determine disease progression in transgenic mice overexpressing mutant superoxide dismutase (mutSOD1) typical of amyotrophic lateral sclerosis patients and that toxicity of mutSOD1 in motor neurons descends from its tendency to associate with mitochondria. To assess whether the neurotoxicity of mutSOD1 is influenced by signals from glia, we challenged motoneuronal cells overexpressing either wild-type or mutant SOD1 with inflammatory cytokines. We have obtained evidence that combined treatment with tumor necrosis factor α and interferon γ increases the fraction of both wtSOD1 and mutSOD1 associated with mitochondria, but these inflammatory cytokines dramatically alter morphological features and functionality of mitochondria only in cells expressing mutSOD1. As an effect downstream the increase in mitochondria-associated mutSOD1, the ratio between reduced and oxidized glutathione further shifts toward the oxidized form in this compartment and a clear death phenotype is evoked upon treatment with inflammatory cytokines. These results suggest that signals coming from non-neuronal cells contribute to death of motor neurons induced by mutSOD1 through reinforcement of mitochondrial damage.

Original languageEnglish
Pages (from-to)454-460
Number of pages7
JournalNeurobiology of Disease
Issue number3
Publication statusPublished - Dec 2008


  • ALS
  • Amyotrophic lateral sclerosis
  • Interferon γ
  • Neuroinflammation
  • SOD
  • TNFα

ASJC Scopus subject areas

  • Neurology


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