Molecular rescue of Dyrk1A overexpression alterations in mice with Fontup® dietary supplement: role of green tea catechins
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- dc.contributor.author Gu, Yuchen
- dc.contributor.author Moroy, Gautier
- dc.contributor.author Paul, Jean-Louis
- dc.contributor.author Rebillat, Anne-Sophie
- dc.contributor.author Dierssen, Mara
- dc.contributor.author Torre Fornell, Rafael de la
- dc.contributor.author Cieuta-Walti, Cécile
- dc.contributor.author Dairou, Julien
- dc.contributor.author Janel, Nathalie
- dc.date.accessioned 2020-03-27T09:27:03Z
- dc.date.available 2020-03-27T09:27:03Z
- dc.date.issued 2020
- dc.description.abstract Epigallocatechin gallate (EGCG) is an inhibitor of DYRK1A, a serine/threonine kinase considered to be a major contributor of cognitive dysfunctions in Down syndrome (DS). Two clinical trials in adult patients with DS have shown the safety and efficacy to improve cognitive phenotypes using commercial green tea extract containing EGCG (45% content). In the present study, we performed a preclinical study using FontUp®, a new nutritional supplement with a chocolate taste specifically formulated for the nutritional needs of patients with DS and enriched with a standardized amount of EGCG in young mice overexpressing Dyrk1A (TgBACDyrk1A). This preparation is differential with previous one used, because its green tea extract has been purified to up 94% EGCG of total catechins. We analyzed the in vitro effect of green tea catechins not only for EGCG, but for others residually contained in FontUp®, on DYRK1A kinase activity. Like EGCG, epicatechin gallate was a noncompetitive inhibitor against ATP, molecular docking computations confirming these results. Oral FontUp® normalized brain and plasma biomarkers deregulated in TgBACDyrk1A, without negative effect on liver and cardiac functions. We compared the bioavailability of EGCG in plasma and brain of mice and have demonstrated that EGCG had well crossed the blood-brain barrier.
- dc.description.sponsorship This work was funded by the Institut Lejeune (grant number EGCG-16RRSMT-IJL-1-JANEZ) and French state funds through the “Agence Nationale de la Recherche” program (grant number ANR-18-CE16-0020 DYRKDOWN). MD is supported by the CRG Severo Ochoa excellence grant (grant number SEV-2016-0571); the CIBER of Rare Diseases; and Secretaria d’Universitats i Recerca del Departament d’Economia I Coneixement de la Generalitat de Catalunya (grant number Grups consolidats 2017SGR926)
- dc.format.mimetype application/pdf
- dc.identifier.citation Gu Y, Moroy G, Paul JL, Rebillat AS, Dierssen M5, de la Torre R et al. Molecular rescue of Dyrk1A overexpression alterations in mice with Fontup® dietary supplement: role of green tea catechins. Int J Mol Sci. 2020 Feb 19; 21(4). pii: E1404. DOI: 10.3390/ijms21041404
- dc.identifier.doi http://dx.doi.org/10.3390/ijms21041404
- dc.identifier.issn 1422-0067
- dc.identifier.uri http://hdl.handle.net/10230/44067
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.ispartof International Journal of Molecular Sciences. 2020 Feb 19;21(4):E1404
- dc.rights © 2020 by Yuchen Gu et al. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Gens
- dc.subject.other Catequina
- dc.subject.other Simulació molecular
- dc.title Molecular rescue of Dyrk1A overexpression alterations in mice with Fontup® dietary supplement: role of green tea catechins
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion