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dc.contributor.author | Natrajan, Muktha S | |
dc.contributor.author | de la Fuente, Alerie G | |
dc.contributor.author | Crawford, Abbe H | |
dc.contributor.author | Linehan, Eimear | |
dc.contributor.author | Nuñez, Vanessa | |
dc.contributor.author | Johnson, Kory R | |
dc.contributor.author | Wu, Tianxia | |
dc.contributor.author | Fitzgerald, Denise C | |
dc.contributor.author | Ricote, Mercedes | |
dc.contributor.author | Bielekova, Bibiana | |
dc.contributor.author | Franklin, Robin J M | |
dc.contributor.author | Natrajan, Muktha S. | |
dc.contributor.author | de la Fuente, Alerie G. | |
dc.contributor.author | Crawford, Abbe H. | |
dc.contributor.author | Johnson, Kory R. | |
dc.contributor.author | Fitzgerald, Denise C. | |
dc.contributor.author | Franklin, Robin J. M. | |
dc.date.accessioned | 2022-11-15T12:00:48Z | |
dc.date.available | 2022-11-15T12:00:48Z | |
dc.date.issued | 2015-12 | |
dc.identifier.citation | Brain . 2015 Dec;138(Pt 12):3581-97. | es_ES |
dc.identifier.issn | 0006-8950 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/15147 | |
dc.description.abstract | The efficiency of central nervous system remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation. In this study, we show that expression of genes involved in the retinoid X receptor pathway are decreased with ageing in both myelin-phagocytosing human monocytes and mouse macrophages using a combination of in vivo and in vitro approaches. Disruption of retinoid X receptor function in young macrophages, using the antagonist HX531, mimics ageing by reducing myelin debris uptake. Macrophage-specific RXRα (Rxra) knockout mice revealed that loss of function in young mice caused delayed myelin debris uptake and slowed remyelination after experimentally-induced demyelination. Alternatively, retinoid X receptor agonists partially restored myelin debris phagocytosis in aged macrophages. The agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in multiple sclerosis patient monocytes to a more youthful profile and enhanced myelin debris phagocytosis by patient cells. These results reveal the retinoid X receptor pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics. | es_ES |
dc.description.sponsorship | This work was supported by grants from the UK Multiple Sclerosis Society, Wellcome-Trust, NINDS/NIH Intramural Research Program, Health Research Board Scholars Program, Gates-Cambridge Scholarship, and Spanish Ministry of Economy and Competitiveness (SAF2012- 31483). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Oxford University Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Phagocytosis | es_ES |
dc.subject.mesh | Adult | es_ES |
dc.subject.mesh | Aging | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Benzoates | es_ES |
dc.subject.mesh | Bexarotene | es_ES |
dc.subject.mesh | Biphenyl Compounds | es_ES |
dc.subject.mesh | Female | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Macrophages | es_ES |
dc.subject.mesh | Male | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, Knockout | es_ES |
dc.subject.mesh | Middle Aged | es_ES |
dc.subject.mesh | Monocytes | es_ES |
dc.subject.mesh | Multiple Sclerosis | es_ES |
dc.subject.mesh | Myelin Sheath | es_ES |
dc.subject.mesh | Retinoid X Receptor alpha | es_ES |
dc.subject.mesh | Signal Transduction | es_ES |
dc.subject.mesh | Tetrahydronaphthalenes | es_ES |
dc.subject.mesh | Transcriptome | es_ES |
dc.subject.mesh | Young Adult | es_ES |
dc.title | Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 26463675 | es_ES |
dc.format.volume | 138 | es_ES |
dc.format.number | Pt 12 | es_ES |
dc.format.page | 3581-97 | es_ES |
dc.identifier.doi | 10.1093/brain/awv289 | es_ES |
dc.contributor.funder | Multiple Sclerosis Society (Reino Unido) | es_ES |
dc.contributor.funder | Wellcome Trust | es_ES |
dc.contributor.funder | NIH - National Institute of Neurological Disorders and Stroke (NINDS) (Estados Unidos) | es_ES |
dc.contributor.funder | Health Research Board Scholars Program | es_ES |
dc.contributor.funder | Gates-Cambridge Scholarship | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1460-2156 | es_ES |
dc.relation.publisherversion | 10.1093/brain/awv289 | es_ES |
dc.identifier.journal | Brain : a journal of neurology | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Señalización de los Receptores Nucleares | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/SAF2012-31483 | es_ES |