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

ABSTRACT: 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 TNF? and several other proinflammatory cytokines. TNF? promotes the generation of many of these cytokines, such as IL6, which raises the possibility that TNF? 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 TNF? contributes to the peripheral inflammation that occurs in the R6/2 mouse model, and whether the in vivo blockade of TNF?, 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 TNF?.

SUBMITTER: Pido-Lopez J 

PROVIDER: S-EPMC6510744 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature