Frataxin deficiency induces Schwann cell inflammation and death

Chunye Lu, Robert Schoenfeld, Yuxi Shan, Hsing Jo Tsai, Bruce Hammock, Gino A Cortopassi

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Mutations in the frataxin gene cause dorsal root ganglion demyelination and neurodegeneration, which leads to Friedreich's ataxia. However the consequences of frataxin depletion have not been measured in dorsal root ganglia or Schwann cells. We knocked down frataxin in several neural cell lines, including two dorsal root ganglia neural lines, 2 neuronal lines, a human oligodendroglial line (HOG) and multiple Schwann cell lines and measured cell death and proliferation. Only Schwann cells demonstrated a significant decrease in viability. In addition to the death of Schwann cells, frataxin decreased proliferation in Schwann, oligodendroglia, and slightly in one neural cell line. Thus the most severe effects of frataxin deficiency were on Schwann cells, which enwrap dorsal root ganglia neurons. Microarray of frataxin-deficient Schwann cells demonstrated strong activations of inflammatory and cell death genes including interleukin-6 and Tumor Necrosis Factor which were confirmed at the mRNA and protein levels. Frataxin knockdown in Schwann cells also specifically induced inflammatory arachidonate metabolites. Anti-inflammatory and anti-apoptotic drugs significantly rescued frataxin-dependent Schwann cell toxicity. Thus, frataxin deficiency triggers inflammatory changes and death of Schwann cells that is inhibitable by inflammatory and anti-apoptotic drugs.

Original languageEnglish (US)
Pages (from-to)1052-1061
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number11
StatePublished - Nov 2009


  • Dorsal root ganglia (DRG) neuron
  • Frataxin
  • Friedreich's ataxia (FRDA)
  • Inflammatory response
  • Schwann cells
  • siRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Medicine(all)


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