Inhibition of tumour necrosis factor alpha in the R6/2 mouse model of Huntington's disease by etanercept treatment

Sci Rep. 2019 May 10;9(1):7202. doi: 10.1038/s41598-019-43627-3.


Huntington's disease (HD) is an inherited neurodegenerative disorder caused by the expansion of the CAG repeat in exon 1 of the huntingtin (HTT) gene, which results in a mutant protein with an extended polyglutamine tract. Inflammation occurs in both the brain and the periphery of HD patients and mouse models, with increases in brain and/or plasma levels of neurotoxic TNFα and several other proinflammatory cytokines. TNFα promotes the generation of many of these cytokines, such as IL6, which raises the possibility that TNFα is central to the inflammatory milieu associated with HD. A number of mouse studies have reported that the suppression of chronic immune activation during HD has beneficial consequences. Here, we investigated whether TNFα contributes to the peripheral inflammation that occurs in the R6/2 mouse model, and whether the in vivo blockade of TNFα, via etanercept treatment, can modify disease progression. We found that etanercept treatment normalised the elevated plasma levels of some cytokines. This did not modify the progression of certain behavioural measures, but slightly ameliorated brain weight loss, possibly related to a reduction in the elevated striatal level of soluble TNFα.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Disease Models, Animal
  • Down-Regulation
  • Etanercept / administration & dosage*
  • Etanercept / pharmacology
  • Exons
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Huntingtin Protein / genetics*
  • Huntington Disease / blood
  • Huntington Disease / drug therapy*
  • Huntington Disease / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics*


  • Anti-Inflammatory Agents, Non-Steroidal
  • HTT protein, human
  • Huntingtin Protein
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Etanercept