Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory disease of the CNS that is associated with demyelination and axonal loss, resulting in severe neurological handicap. Current MS therapies mostly target neuroinflammation but have only a little impact on CNS myelin repair. Progress toward treatments that enh...

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Authors: Blanchard, Benoit, Heurtaux, Tony, Garcia, Corina Ileana, Moll, Natalia M., Caillava, Céline, Grandbarbe, Luc, Klosptein, Armelle, Kerninon, Christophe, Frah, Magali, Coowar, Djalil, Baron-van Evercooren, Anne, Morga, Eleonora, Heuschling, Paul, Nait Oumesmar, Brahim
Format: article
Status:Published version
Publication Date:2013
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/1723
Online Access:http://hdl.handle.net/11336/1723
Access Level:Open access
Keyword:Tfa-12
Oligodendrocytes
Multiple Sclerosis
Myelin
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.2
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network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple Sclerosis
title Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple Sclerosis
spellingShingle Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple Sclerosis
Blanchard, Benoit
Tfa-12
Oligodendrocytes
Multiple Sclerosis
Myelin
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
title_short Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple Sclerosis
title_full Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple Sclerosis
title_fullStr Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple Sclerosis
title_full_unstemmed Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple Sclerosis
title_sort Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple Sclerosis
dc.creator.none.fl_str_mv Blanchard, Benoit
Heurtaux, Tony
Garcia, Corina Ileana
Moll, Natalia M.
Caillava, Céline
Grandbarbe, Luc
Klosptein, Armelle
Kerninon, Christophe
Frah, Magali
Coowar, Djalil
Baron-van Evercooren, Anne
Morga, Eleonora
Heuschling, Paul
Nait Oumesmar, Brahim
author Blanchard, Benoit
author_facet Blanchard, Benoit
Heurtaux, Tony
Garcia, Corina Ileana
Moll, Natalia M.
Caillava, Céline
Grandbarbe, Luc
Klosptein, Armelle
Kerninon, Christophe
Frah, Magali
Coowar, Djalil
Baron-van Evercooren, Anne
Morga, Eleonora
Heuschling, Paul
Nait Oumesmar, Brahim
author_role author
author2 Heurtaux, Tony
Garcia, Corina Ileana
Moll, Natalia M.
Caillava, Céline
Grandbarbe, Luc
Klosptein, Armelle
Kerninon, Christophe
Frah, Magali
Coowar, Djalil
Baron-van Evercooren, Anne
Morga, Eleonora
Heuschling, Paul
Nait Oumesmar, Brahim
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Tfa-12
Oligodendrocytes
Multiple Sclerosis
Myelin
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
topic Tfa-12
Oligodendrocytes
Multiple Sclerosis
Myelin
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
description Multiple sclerosis (MS) is an inflammatory disease of the CNS that is associated with demyelination and axonal loss, resulting in severe neurological handicap. Current MS therapies mostly target neuroinflammation but have only a little impact on CNS myelin repair. Progress toward treatments that enhance remyelination would therefore represent major advances in MS treatment. Here, we examined the ability of TFA-12, a new synthetic compound belonging to tocopherol long-chain fatty alcohols, to promote oligodendrocyte regeneration and remyelination in experimental models of MS. We showed that TFA-12 significantly ameliorates neurological deficit and severity of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) in mice. Histological evaluation of mouse EAE spinal cords showed that TFA-12 treatment reduces inflammation, astrogliosis, and myelin loss. Additionally, we demonstrated that TFA-12 accelerates remyelination of focal demyelinated lesions induced by lysolecithin injections.Wealso found that this compound induces the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes through the inhibition of the Notch/Jagged1 signaling pathway. Altogether, our data provide important proof of principle indicating that TFA-12 could be a potential therapeutic compound for myelin repair in MS.
publishDate 2013
dc.date.none.fl_str_mv 2013-07-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/1723
Blanchard, Benoit; Heurtaux, Tony; Garcia, Corina Ileana; Moll, Natalia M.; Caillava, Céline; et al.; Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple Sclerosis; Society for Neuroscience; Journal of Neuroscience; 33; 28; 10-7-2013; 11633-11642
0270-6474
1529-2401
url http://hdl.handle.net/11336/1723
identifier_str_mv Blanchard, Benoit; Heurtaux, Tony; Garcia, Corina Ileana; Moll, Natalia M.; Caillava, Céline; et al.; Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple Sclerosis; Society for Neuroscience; Journal of Neuroscience; 33; 28; 10-7-2013; 11633-11642
0270-6474
1529-2401
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/doi:10.1523/JNEUROSCI.0774-13.2013
info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/33/28/11633.full.pdf+html
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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spelling Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple SclerosisBlanchard, BenoitHeurtaux, TonyGarcia, Corina IleanaMoll, Natalia M.Caillava, CélineGrandbarbe, LucKlosptein, ArmelleKerninon, ChristopheFrah, MagaliCoowar, DjalilBaron-van Evercooren, AnneMorga, EleonoraHeuschling, PaulNait Oumesmar, BrahimTfa-12OligodendrocytesMultiple SclerosisMyelinhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Multiple sclerosis (MS) is an inflammatory disease of the CNS that is associated with demyelination and axonal loss, resulting in severe neurological handicap. Current MS therapies mostly target neuroinflammation but have only a little impact on CNS myelin repair. Progress toward treatments that enhance remyelination would therefore represent major advances in MS treatment. Here, we examined the ability of TFA-12, a new synthetic compound belonging to tocopherol long-chain fatty alcohols, to promote oligodendrocyte regeneration and remyelination in experimental models of MS. We showed that TFA-12 significantly ameliorates neurological deficit and severity of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) in mice. Histological evaluation of mouse EAE spinal cords showed that TFA-12 treatment reduces inflammation, astrogliosis, and myelin loss. Additionally, we demonstrated that TFA-12 accelerates remyelination of focal demyelinated lesions induced by lysolecithin injections.Wealso found that this compound induces the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes through the inhibition of the Notch/Jagged1 signaling pathway. Altogether, our data provide important proof of principle indicating that TFA-12 could be a potential therapeutic compound for myelin repair in MS.Fil: Blanchard, Benoit. Universite Pierre et Marie Curie; Francia; . Centre National de la Recherche Scientifique. Unités Mixtes de Recherche; Francia; . Institut National de la Santé et de la Recherche Médicale; FranciaFil: Heurtaux, Tony. Université du Luxembourg. Faculté des Sciences, de la Technologie et de la Communication. Laboratoire de Neurobiologie. Life Sciences Research Unit; Luxemburgo;Fil: Garcia, Corina Ileana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Institut National de la Santé et de la Recherche Médicale; Francia. Universite Pierre et Marie Curie; Francia;Fil: Moll, Natalia M.. Institut National de la Santé et de la Recherche Médicale; . Universite Pierre et Marie Curie; Francia; . Centre National de la Recherche Scientifique. Unités Mixtes de Recherche; Francia;Fil: Caillava, Céline. Institut National de la Santé et de la Recherche Médicale; . Universite Pierre et Marie Curie; Francia; . Centre National de la Recherche Scientifique. Unités Mixtes de Recherche; Francia;Fil: Grandbarbe, Luc. Université du Luxembourg. Faculté des Sciences, de la Technologie et de la Communication. Laboratoire de Neurobiologie. Life Sciences Research Unit; Luxemburgo;Fil: Klosptein, Armelle. Institut National de la Santé et de la Recherche Médicale; . Universite Pierre et Marie Curie; Francia; . Centre National de la Recherche Scientifique. Unités Mixtes de Recherche; Francia;Fil: Kerninon, Christophe. Institut National de la Santé et de la Recherche Médicale; . Universite Pierre et Marie Curie; Francia; . Centre National de la Recherche Scientifique. Unités Mixtes de Recherche; Francia;Fil: Frah, Magali. Institut National de la Santé et de la Recherche Médicale; . Universite Pierre et Marie Curie; Francia; . Centre National de la Recherche Scientifique. Unités Mixtes de Recherche; Francia;Fil: Coowar, Djalil. AxoGlia Therapeutics; Luxemburgo;Fil: Baron-van Evercooren, Anne. Institut National de la Santé et de la Recherche Médicale; . Universite Pierre et Marie Curie; Francia; . Centre National de la Recherche Scientifique. Unités Mixtes de Recherche; Francia;Fil: Morga, Eleonora. Université du Luxembourg. Faculté des Sciences, de la Technologie et de la Communication. Laboratoire de Neurobiologie. Life Sciences Research Unit; Luxemburgo;Fil: Heuschling, Paul. Université du Luxembourg. Faculté des Sciences, de la Technologie et de la Communication. Laboratoire de Neurobiologie. Life Sciences Research Unit; Luxemburgo;Fil: Nait Oumesmar, Brahim. Institut National de la Santé et de la Recherche Médicale; . Universite Pierre et Marie Curie; Francia; . Centre National de la Recherche Scientifique. Unités Mixtes de Recherche; Francia;Society for Neuroscience2013-07-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/1723Blanchard, Benoit; Heurtaux, Tony; Garcia, Corina Ileana; Moll, Natalia M.; Caillava, Céline; et al.; Tocopherol Derivative TFA-12 Promotes Myelin Repair in Experimental Models of Multiple Sclerosis; Society for Neuroscience; Journal of Neuroscience; 33; 28; 10-7-2013; 11633-116420270-64741529-2401enginfo:eu-repo/semantics/altIdentifier/doi/doi:10.1523/JNEUROSCI.0774-13.2013info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/33/28/11633.full.pdf+htmlinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:40:30Zoai:ri.conicet.gov.ar:11336/1723instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 13:40:31.03CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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