Effects of isoxazolo-pyridinone 7e, a potent activator of the nurr1 signaling pathway, on experimental autoimmune encephalomyelitis in mice

Francesca Montarolo, Chiara Raffaele, Simona Perga, Serena Martire, Annamaria Finardi, Roberto Furlan, Samuel Hintermann, Antonio Bertolotto

Research output: Contribution to journalArticlepeer-review

Abstract

Multiple sclerosis (MS) is an autoimmune chronic disease of the central nervous system (CNS) characterized by immunemediated inflammation, demyelination and subsequent axonal damage. Gene expression profiling showed that Nurr1, an orphan nuclear receptor, is down-regulated in peripheral blood mononuclear cells of MS patients. Nurr1 exerts an antiinflammatory role repressing the activity of the pro-inflammatory transcription factor NF-kB. Here, we report that the preventive treatment with isoxazolo-pyridinone 7e, an activator of Nurr1 signaling pathway, reduces the incidence and the severity of a MS murine model, i.e. experimental autoimmune encephalomyelitis (EAE). The compound is able to attenuate inflammation and neurodegeneration in spinal cords of EAE mice by an NF-kB pathway-dependent process.

Original languageEnglish
Article numbere108791
JournalPLoS One
Volume9
Issue number9
DOIs
Publication statusPublished - Sep 1 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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