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dc.contributor.authorRiancho Zarrabeitia, Javier
dc.contributor.authorRuiz Soto, María 
dc.contributor.authorBerciano Blanco, María Teresa 
dc.contributor.authorBerciano Blanco, José Ángel 
dc.contributor.authorLafarga Coscojuela, Miguel Ángel 
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.date.accessioned2015-09-08T06:51:15Z
dc.date.available2015-09-08T06:51:15Z
dc.date.issued2015-07-01
dc.identifier.issn1662-5102
dc.identifier.urihttp://hdl.handle.net/10902/7101
dc.description.abstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness and muscle atrophy related to the loss of upper and lower motor neurons (MNs) without a curative treatment. There is experimental evidence suggesting that retinoids may be involved in ALS pathogenesis. Bexarotene (Bxt) is a retinoid-X receptor agonist used in the treatment of cutaneous lymphoma with a favorable safety profile whose effects have been recently investigated in other neurodegenerative diseases. In this study, we analyze the potential therapeutic effect of Bxt in the SOD1(G93A) mouse model of ALS. Mice were treated with Bxt or vehicle five times per week from day 60 onward. Survival, weight, and neuromuscular function studies together with histological and biochemical analyses were performed. Bxt significantly delayed motor function deterioration, ameliorated the loss of body weight, and extended mice survival up to 30% of the symptomatic period. Histological analyses of the lumbosacral spinal cord revealed that Bxt markedly delayed the early motor-neuron degeneration occurring at presymptomatic stages in ALS-transgenic mice. Bxt treatment contributed to preserve the MN homeostasis in the SOD1(G93A) mice. Particularly, it reduced the neuronal loss and the chromatolytic response, induced nucleolar hypertrophy, decreased the formation of ubiquitylated inclusions, and modulated the lysosomal response. As an agonist of the retinoic-X receptor (RXR) pathway, Bxt notably increased the nuclear expression of the RXRα throughout transcriptionally active euchromatin domains. Bxt also contributed to protect the MN environment by reducing reactive astrogliosis and preserving perisomatic synapsis. Overall, these neuroprotective effects suggest that treatment with Bxt could be useful in ALS, particularly in those cases related to SOD1 mutations.es_ES
dc.format.extent17 p.es_ES
dc.language.isoenges_ES
dc.publisherFrontierses_ES
dc.rightsAtribución 3.0 España*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.sourceFrontiers in Cellular Neuroscience. 2015 Jul 1;9:250es_ES
dc.subject.otherG93ASOD1es_ES
dc.subject.otherAmyotrophic lateral sclerosises_ES
dc.subject.otherBexarotenees_ES
dc.subject.otherMousees_ES
dc.subject.otherProteostasises_ES
dc.subject.otherRetinoid-X receptores_ES
dc.titleNeuroprotective Effect of Bexarotene in the SOD1(G93A) Mouse Model of Amyotrophic Lateral Sclerosises_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessRightsopenAccesses_ES
dc.identifier.DOI10.3389/fncel.2015.00250
dc.type.versionpublishedVersiones_ES


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Atribución 3.0 EspañaExcept where otherwise noted, this item's license is described as Atribución 3.0 España