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Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene

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dc.contributor.author Ortega, Mireia
dc.contributor.author De Toma, Ilario
dc.contributor.author Fernández-Blanco, Álvaro
dc.contributor.author Calderón Moruno, Anna
dc.contributor.author Barahona, Lucía
dc.contributor.author Trullàs, Ramón
dc.contributor.author Sabidó Aguadé, Eduard, 1981-
dc.contributor.author Dierssen, Mara
dc.date.accessioned 2023-03-07T07:12:44Z
dc.date.available 2023-03-07T07:12:44Z
dc.date.issued 2022
dc.identifier.citation Ortega M, De Toma I, Fernández-Blanco Á, Calderón A, Barahona L, Trullàs R, Sabidó E, Dierssen M. Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene. Front Mol Neurosci. 2022 Dec 15;15:1015220. DOI: 10.3389/fnmol.2022.1015220
dc.identifier.issn 1662-5099
dc.identifier.uri http://hdl.handle.net/10230/56066
dc.description.abstract Introduction: DYRK1A is a dual-specificity kinase that is overexpressed in Down syndrome (DS) and plays a key role in neurogenesis, neuronal differentiation and function, cognitive phenotypes, and aging. Dyrk1A has also been implicated in cerebellar abnormalities observed in association with DS, and normalization of Dyrk1A dosage rescues granular and Purkinje cell densities in a trisomic DS mouse model. However, the underlying molecular mechanisms governing these processes are unknown. Methods: To shed light on the effects of Dyrk1A overexpression in the cerebellum, here we investigated the cerebellar proteome in transgenic Dyrk1A overexpressing mice in basal conditions and after treatment with green tea extract containing epigallocatechin-3-gallate (EGCG), a DYRK1A inhibitor. Results and discussion: Our results showed that Dyrk1A overexpression alters oxidative phosphorylation and mitochondrial function in the cerebellum of transgenic mice. These alterations are significantly rescued upon EGCG-containing green tea extract treatment, suggesting that its effects in DS could depend in part on targeting mitochondria, as shown by the partially restoration by the treatment of the increased mtDNA copy number in TG non-treated mice.
dc.description.sponsorship This research was funded by the Agencia Estatal de Investigación (PID2019-110755RB-I00/AEI/10.13039/501100011033), the European Union’s Horizon 2020 Framework Programme under grant agreement no 848077. This reflects only the author’s view and the European Commission is not responsible for any use that may be made of the information it contains. Jerôme Lejeune Foundation (grant number 2002), NIH Blueprint for Neuroscience Research (grant number: 1R01EB 028159-01), Marató TV3 (#2016/20-30), and EU Joint Programme—Neurodegenerative Disease Research (Heroes AC170006). The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech), and it is supported by “Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” (2017SGR595). The CRG acknowledges the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Programme/Generalitat de Catalunya. The CIBER of Rare Diseases (CIBERER) is an initiative of the ISCIII.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Frontiers
dc.relation.ispartof Front Mol Neurosci. 2022 Dec 15;15:1015220
dc.rights © 2022 Ortega, De Toma, Fernández-Blanco, Calderón, Barahona, Trullàs, Sabidó and Dierssen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3389/fnmol.2022.1015220
dc.subject.keyword DYRK1A
dc.subject.keyword Down syndrome
dc.subject.keyword Cerebellum
dc.subject.keyword Mitochondria
dc.subject.keyword Oxidative phosphorylation system
dc.subject.keyword Proteomics
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/848077
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110755RB-I00
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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