{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:59:59Z","timestamp":1790510399673,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T00:00:00Z","timestamp":1582070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u00ae, 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\u00ae, on DYRK1A kinase activity. Like EGCG, epicatechin gallate was a noncompetitive inhibitor against ATP, molecular docking computations confirming these results. Oral FontUp\u00ae 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.<\/jats:p>","DOI":"10.3390\/ijms21041404","type":"journal-article","created":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T03:20:03Z","timestamp":1582168803000},"page":"1404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Molecular Rescue of Dyrk1A Overexpression Alterations in Mice with Fontup\u00ae Dietary Supplement: Role of Green Tea Catechins"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-2264","authenticated-orcid":false,"given":"Yuchen","family":"Gu","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautier","family":"Moroy","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, BFA, UMR 8251, CNRS, ERL U1133, Inserm, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Louis","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Georges Pompidou European Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Sophie","family":"Rebillat","sequence":"additional","affiliation":[{"name":"Institut J\u00e9r\u00f4me Lejeune, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Dierssen","sequence":"additional","affiliation":[{"name":"Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain"},{"name":"Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6765-1866","authenticated-orcid":false,"given":"Rafael","family":"de la Torre","sequence":"additional","affiliation":[{"name":"Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain"},{"name":"Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program, IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3806-4141","authenticated-orcid":false,"given":"C\u00e9cile","family":"Cieuta-Walti","sequence":"additional","affiliation":[{"name":"Institut J\u00e9r\u00f4me Lejeune, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Dairou","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologique, UMR 8601, CNRS, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Janel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0079-6603(08)60503-6","article-title":"Structural and functional characteristics of dyrk, a novel subfamily of protein kinases with dual specificity","volume":"62","author":"Becker","year":"1998","journal-title":"Prog. 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