Type-1 interferons contribute to the neuroinflammatory response and disease progression of the MPTP mouse model of Parkinson's disease

Bevan S. Main, Moses Zhang, Kate M Brody, Scott Ayton, Tony Frugier, David Steer, David Finkelstein, Peter J. Crack, Juliet M. Taylor

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)

Abstract

Type-1 interferons (IFNs) are pleiotropic cytokines with a critical role in the initiation and regulation of the pro-inflammatory response. However, the contribution of the type-1 IFNs to CNS disorders, specifically chronic neuropathologies such as Parkinson's disease is still unknown. Here, we report increased type-1 IFN signaling in both post mortem human Parkinson's disease samples and in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model. In response to MPTP, mice lacking the type-1 IFN receptor (IFNAR1−/−) displayed decreased type-1 IFN signaling, an attenuated pro-inflammatory response and reduced loss of dopaminergic neurons. The neuroprotective potential of targeting the type-1 IFN pathway was confirmed by reduced neuroinflammation and DA cell death in mice treated with a blocking monoclonal IFNAR1 (MAR-1) antibody. The MPTP/MAR-1 treated mice also displayed increased striatal dopamine levels and improved behavioural outcomes compared to their MPTP/IgG controls. These data, implicate for the first time, a deleterious role for the type-1 IFNs as key modulators of the early neuroinflammatory response and therefore the neuronal cell death in Parkinson's disease. 

Original languageEnglish
Pages (from-to)1590-1604
Number of pages15
JournalGLIA
Volume64
Issue number9
DOIs
Publication statusPublished - 1 Sep 2016

Keywords

  • interferons
  • microglia
  • MPTP
  • neuroinflammation
  • Parkinson's disease

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