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Effects of Isoxazolo-Pyridinone 7e, a Potent Activator of the Nurr1 Signaling Pathway, on Experimental Autoimmune Encephalomyelitis in Mice

Montarolo, F and Raffaele, C and Perga, S and Martire, S and Finardi, A and Furlan, R and Hintermann, S and Bertolotto, A (2014) Effects of Isoxazolo-Pyridinone 7e, a Potent Activator of the Nurr1 Signaling Pathway, on Experimental Autoimmune Encephalomyelitis in Mice. PLoS ONE. e108791-.

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

Item Type: Article
Additional Information: NIBR author: Hintermann, S institute: NIBR contributor address: 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, ItalyDivision of Neuroscience, Experimental Neurology Institute (INSPE), San Raffaele Scientific Institute, Milan, ItalyNeurobiology Unit, Neurologia 2 - CRESM (Regional Referring Center of Multiple Sclerosis), Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin and AOU San Luigi, Orbassano, Torino, ItalyNeurobiology Unit, Neurologia 2 - CRESM (Regional Referring Center of Multiple Sclerosis), Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin and AOU San Luigi, Orbassano, Torino, ItalyDivision of Neuroscience, Experimental Neurology Institute (INSPE), San Raffaele Scientific Institute, Milan, ItalyDivision of Neuroscience, Experimental Neurology Institute (INSPE), San Raffaele Scientific Institute, Milan, ItalyGlobal Discovery Chemistry, Novartis Institutes for BioMedical Research, Basel, SwitzerlandNeurobiology 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
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/24239

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