2026-06-14T05:08:18Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/151472024-09-27T08:02:26Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Natrajan, Muktha S
author
de la Fuente, Alerie G
author
Crawford, Abbe H
author
Linehan, Eimear
author
Nuñez, Vanessa
author
Johnson, Kory R
author
Wu, Tianxia
author
Fitzgerald, Denise C
author
Ricote, Mercedes
author
Bielekova, Bibiana
author
Franklin, Robin J M
author
Natrajan, Muktha S.
author
de la Fuente, Alerie G.
author
Crawford, Abbe H.
author
Johnson, Kory R.
author
Fitzgerald, Denise C.
author
Franklin, Robin J. M.
funder
Multiple Sclerosis Society (Reino Unido)
funder
Wellcome Trust
funder
NIH - National Institute of Neurological Disorders and Stroke (NINDS) (Estados Unidos)
funder
Health Research Board Scholars Program
funder
Gates-Cambridge Scholarship
funder
Ministerio de Economía y Competitividad (España)
2022-11-15T12:00:48Z
2022-11-15T12:00:48Z
2015-12
Brain . 2015 Dec;138(Pt 12):3581-97.
10.1093/brain/awv289
1460-2156
0006-8950
Brain : a journal of neurology
26463675
http://hdl.handle.net/20.500.12105/15147
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.
eng
Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination.
journal article
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URL
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File
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Brain 2015 Retinoid X receptor activation RICOTE.pdf
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https://repisalud.isciii.es/bitstreams/20115cee-8c89-4bac-adf8-c1e11c20bc48/download
File
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text/plain
Brain 2015 Retinoid X receptor activation RICOTE.pdf.txt