title: Effects of isoxazolo-pyridinone 7e, a potent activator of the Nurr1 signaling pathway, on experimental autoimmune encephalomyelitis in mice.
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.
authors.affiliation: 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.
authors.forename: Francesca
authors.initials: F
authors.lastname: Montarolo
authors.affiliation: Division of Neuroscience, Experimental Neurology Institute (INSPE), San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Raffaele
authors.affiliation: 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.
authors.forename: Simona
authors.initials: S
authors.lastname: Perga
authors.affiliation: 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.
authors.forename: Serena
authors.initials: S
authors.lastname: Martire
authors.affiliation: Division of Neuroscience, Experimental Neurology Institute (INSPE), San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Finardi
authors.affiliation: Division of Neuroscience, Experimental Neurology Institute (INSPE), San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Furlan
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Hintermann
authors.affiliation: 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.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D003711:Demyelinating Diseases / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007555:Isoxazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D016328:NF-kappa B / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism*; D010080:Oxazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments; D011744:Pyrimidinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: C000601469:6-(4-((2-methoxyethoxy)methyl)phenyl)-5-methyl-3-phenylisoxazolo(4,5-c)pyridin-4(5H)-one; D007555:Isoxazoles; D063308:Myelin-Oligodendrocyte Glycoprotein; D016328:NF-kappa B; C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010080:Oxazoles; D010446:Peptide Fragments; D011744:Pyrimidinones; C445081:myelin oligodendrocyte glycoprotein (35-55)