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http://hdl.handle.net/1942/25930
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DC Field | Value | Language |
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dc.contributor.author | Llufriu-Dabén, Gemma | - |
dc.contributor.author | Carrete, Alex | - |
dc.contributor.author | Chierto, Elena | - |
dc.contributor.author | MAILLEUX, Jo | - |
dc.contributor.author | Camand, Emeline | - |
dc.contributor.author | Simon, Anne | - |
dc.contributor.author | VANMIERLO, Tim | - |
dc.contributor.author | Rose, Christiane | - |
dc.contributor.author | Allinquant, Bernadette | - |
dc.contributor.author | HENDRIKS, Jerome | - |
dc.contributor.author | Massaad, Charbel | - |
dc.contributor.author | Meffre, Delphine | - |
dc.contributor.author | Jafarian-Tehrania, Mehrnaz | - |
dc.date.accessioned | 2018-04-20T13:29:39Z | - |
dc.date.available | 2018-04-20T13:29:39Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Neurobiology of disease, 109(A), p. 11-24 | - |
dc.identifier.issn | 0969-9961 | - |
dc.identifier.uri | http://hdl.handle.net/1942/25930 | - |
dc.description.abstract | Remyelination is an endogenous regenerative process of myelin repair in the central nervous system (CNS) with limited efficacy in demyelinating disorders. As strategies enhancing endogenous remyelination become a therapeutic challenge, we have focused our study on α-secretase-induced sAPPα release, a soluble endogenous protein with neuroprotective and neurotrophic properties. However, the role of sAPPα in remyelination is not known. Therefore, we investigated the remyelination potential of α-secretase-induced sAPPα release following CNS demyelination in mice. Acute demyelination was induced by feeding mice with cuprizone (CPZ) for 5 weeks. To test the protective effect and the remyelination potential of etazolate, an α-secretase activator, we designed two treatment protocols. Etazolate was administrated either during the last two weeks or at the end of the CPZ intoxication. In both protocols, etazolate restored the number of myelinated axons in corpus callosum with a corresponding increase in the amount of MBP, one of the major myelin proteins in the brain. We also performed ex vivo studies to decipher etazolate's mechanism of action in a lysolecithin-induced demyelination model using organotypic culture of cerebellar slices. Etazolate treatment was able to i) enhance the release of sAPPα in the culture media of demyelinated slices, ii) protect myelinated axons from demyelination, iii) increase the number of mature oligodendrocytes, iv) promote the reappearance of the paired Caspr+ adjacent to the nodes of Ranvier and v) increase the percentage of myelinated axons with short internodes, an indicator of remyelination. Etazolate failed to promote all the aforementioned effects in the presence of GI254023X, an α-secretase inhibitor. Moreover, the protective effects of etazolate in demyelinated slices were mimicked by sAPPα treatment in a dose-dependent manner. In conclusion, etazolate-induced sAPPα release protects myelinated axons from demyelination while also promoting remyelination. This work, thus, highlights the therapeutic potential of strategies that enhance sAPPα release in demyelinating disorders. | - |
dc.description.sponsorship | We acknowledge the non-profit organizations “Fondation des Gueules Cassées” (grants 47-2015, 47-2016 to MJT; PhD fellowship 55-2014 to GLD; PhD fellowship 48-2015, 48-2016 to AC), “Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques” (grant AO2015-meffre to DM), Paris Descartes University and INSERM (Institut National de la Santé Et de la Recherche Médicale) for financially supporting this work. | - |
dc.language.iso | en | - |
dc.rights | © 2017 Elsevier Inc. All rights reserved. | - |
dc.subject.other | etazolate; α-Secretase; sAPPα; myelin; oligodendrocyte; de/remyelination; white matter | - |
dc.title | Targeting demyelination via α-secretases promoting sAPPα release to enhance remyelination in central nervous system | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 24 | - |
dc.identifier.issue | A | - |
dc.identifier.spage | 11 | - |
dc.identifier.volume | 109 | - |
local.bibliographicCitation.jcat | A1 | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.identifier.doi | 10.1016/j.nbd.2017.09.008 | - |
dc.identifier.isi | 000418877600002 | - |
item.fulltext | With Fulltext | - |
item.fullcitation | Llufriu-Dabén, Gemma; Carrete, Alex; Chierto, Elena; MAILLEUX, Jo; Camand, Emeline; Simon, Anne; VANMIERLO, Tim; Rose, Christiane; Allinquant, Bernadette; HENDRIKS, Jerome; Massaad, Charbel; Meffre, Delphine & Jafarian-Tehrania, Mehrnaz (2018) Targeting demyelination via α-secretases promoting sAPPα release to enhance remyelination in central nervous system. In: Neurobiology of disease, 109(A), p. 11-24. | - |
item.accessRights | Open Access | - |
item.validation | ecoom 2019 | - |
item.contributor | Llufriu-Dabén, Gemma | - |
item.contributor | Carrete, Alex | - |
item.contributor | Chierto, Elena | - |
item.contributor | MAILLEUX, Jo | - |
item.contributor | Camand, Emeline | - |
item.contributor | Simon, Anne | - |
item.contributor | VANMIERLO, Tim | - |
item.contributor | Rose, Christiane | - |
item.contributor | Allinquant, Bernadette | - |
item.contributor | HENDRIKS, Jerome | - |
item.contributor | Massaad, Charbel | - |
item.contributor | Meffre, Delphine | - |
item.contributor | Jafarian-Tehrania, Mehrnaz | - |
crisitem.journal.issn | 0969-9961 | - |
crisitem.journal.eissn | 1095-953X | - |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
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neurobiol of disease 2018.pdf Restricted Access | Published version | 3.04 MB | Adobe PDF | View/Open Request a copy |
llufriudabn2018.pdf | Peer-reviewed author version | 1.78 MB | Adobe PDF | View/Open |
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