Effects of isoxazolo-pyridinone 7e, a potent activator of the Nurr1 signaling pathway, on experimental autoimmune encephalomyelitis in mice

  • PLoS One. 2014 Sep 29;9(9):e108791. doi: 10.1371/journal.pone.0108791.
Francesca Montarolo  1 ,  Chiara Raffaele  2 ,  Simona Perga  1 ,  Serena Martire  1 ,  Annamaria Finardi  2 ,  Roberto Furlan  2 ,  Samuel Hintermann  3 ,  Antonio Bertolotto  1
Affiliations
  • 1. Neurobiology Unit, Neurologia 2 - CRESM (Regional Referring Center of Multiple Sclerosis), Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin and AOU San Luigi, Orbassano, Torino, Italy.
  • 2. Division of Neuroscience, Experimental Neurology Institute (INSPE), San Raffaele Scientific Institute, Milan, Italy.
  • 3. Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Basel, Switzerland.
PMID: 25265488 DOI: 10.1371/journal.pone.0108791
Abstract

Multiple sclerosis (MS) is an autoimmune chronic disease of the central nervous system (CNS) characterized by immune-mediated 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 anti-inflammatory 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.

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