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.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.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.doi http://dx.doi.org/10.3389/fnmol.2022.1015220
  • dc.identifier.issn 1662-5099
  • dc.identifier.uri http://hdl.handle.net/10230/56066
  • dc.language.iso eng
  • dc.publisher Frontiers
  • dc.relation.ispartof Front Mol Neurosci. 2022 Dec 15;15:1015220
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/848077
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110755RB-I00
  • 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.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • 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.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.type.version info:eu-repo/semantics/publishedVersion

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