Cargando…
Effects of Isoxazolo-Pyridinone 7e, a Potent Activator of the Nurr1 Signaling Pathway, on Experimental Autoimmune Encephalomyelitis in Mice
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 monon...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4181297/ https://www.ncbi.nlm.nih.gov/pubmed/25265488 http://dx.doi.org/10.1371/journal.pone.0108791 |
_version_ | 1782337356666241024 |
---|---|
author | Montarolo, Francesca Raffaele, Chiara Perga, Simona Martire, Serena Finardi, Annamaria Furlan, Roberto Hintermann, Samuel Bertolotto, Antonio |
author_facet | Montarolo, Francesca Raffaele, Chiara Perga, Simona Martire, Serena Finardi, Annamaria Furlan, Roberto Hintermann, Samuel Bertolotto, Antonio |
author_sort | Montarolo, Francesca |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4181297 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41812972014-10-07 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 PLoS One Research Article 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. Public Library of Science 2014-09-29 /pmc/articles/PMC4181297/ /pubmed/25265488 http://dx.doi.org/10.1371/journal.pone.0108791 Text en © 2014 Montarolo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article 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 |
title | Effects of Isoxazolo-Pyridinone 7e, a Potent Activator of the Nurr1 Signaling Pathway, on Experimental Autoimmune Encephalomyelitis in Mice |
title_full | Effects of Isoxazolo-Pyridinone 7e, a Potent Activator of the Nurr1 Signaling Pathway, on Experimental Autoimmune Encephalomyelitis in Mice |
title_fullStr | Effects of Isoxazolo-Pyridinone 7e, a Potent Activator of the Nurr1 Signaling Pathway, on Experimental Autoimmune Encephalomyelitis in Mice |
title_full_unstemmed | Effects of Isoxazolo-Pyridinone 7e, a Potent Activator of the Nurr1 Signaling Pathway, on Experimental Autoimmune Encephalomyelitis in Mice |
title_short | Effects of Isoxazolo-Pyridinone 7e, a Potent Activator of the Nurr1 Signaling Pathway, on Experimental Autoimmune Encephalomyelitis in Mice |
title_sort | effects of isoxazolo-pyridinone 7e, a potent activator of the nurr1 signaling pathway, on experimental autoimmune encephalomyelitis in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4181297/ https://www.ncbi.nlm.nih.gov/pubmed/25265488 http://dx.doi.org/10.1371/journal.pone.0108791 |
work_keys_str_mv | AT montarolofrancesca effectsofisoxazolopyridinone7eapotentactivatorofthenurr1signalingpathwayonexperimentalautoimmuneencephalomyelitisinmice AT raffaelechiara effectsofisoxazolopyridinone7eapotentactivatorofthenurr1signalingpathwayonexperimentalautoimmuneencephalomyelitisinmice AT pergasimona effectsofisoxazolopyridinone7eapotentactivatorofthenurr1signalingpathwayonexperimentalautoimmuneencephalomyelitisinmice AT martireserena effectsofisoxazolopyridinone7eapotentactivatorofthenurr1signalingpathwayonexperimentalautoimmuneencephalomyelitisinmice AT finardiannamaria effectsofisoxazolopyridinone7eapotentactivatorofthenurr1signalingpathwayonexperimentalautoimmuneencephalomyelitisinmice AT furlanroberto effectsofisoxazolopyridinone7eapotentactivatorofthenurr1signalingpathwayonexperimentalautoimmuneencephalomyelitisinmice AT hintermannsamuel effectsofisoxazolopyridinone7eapotentactivatorofthenurr1signalingpathwayonexperimentalautoimmuneencephalomyelitisinmice AT bertolottoantonio effectsofisoxazolopyridinone7eapotentactivatorofthenurr1signalingpathwayonexperimentalautoimmuneencephalomyelitisinmice |