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 journalArticle

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

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Pyridones
Autoimmune Experimental Encephalomyelitis
NF-kappa B
sclerosis
encephalitis
Multiple Sclerosis
Nuclear Receptor Subfamily 4, Group A, Member 2
transcription factor NF-kappa B
mice
Neurology
inflammation
Gene expression
Inflammation
Blood
Anti-Inflammatory Agents
Gene Expression Profiling
Demyelinating Diseases
mononuclear leukocytes
chronic diseases
spinal cord

ASJC Scopus subject areas

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

Cite this

Effects of isoxazolo-pyridinone 7e, a potent activator of the nurr1 signaling pathway, on experimental autoimmune encephalomyelitis in mice. / Montarolo, Francesca; Raffaele, Chiara; Perga, Simona; Martire, Serena; Finardi, Annamaria; Furlan, Roberto; Hintermann, Samuel; Bertolotto, Antonio.

In: PLoS One, Vol. 9, No. 9, e108791, 01.09.2014.

Research output: Contribution to journalArticle

Montarolo, Francesca ; Raffaele, Chiara ; Perga, Simona ; Martire, Serena ; Finardi, Annamaria ; Furlan, Roberto ; Hintermann, Samuel ; Bertolotto, Antonio. / Effects of isoxazolo-pyridinone 7e, a potent activator of the nurr1 signaling pathway, on experimental autoimmune encephalomyelitis in mice. In: PLoS One. 2014 ; Vol. 9, No. 9.
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