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

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...

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Autores: Ortega, Mireia, Toma, Ilario de, Fernández Blanco, Álvaro, Calderón, Anna, Barahona, Lucía, Trullàs i Oliva, Ramon, Sabidó, Eduard, Dierssen, Mara
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/201449
Acceso en línea:https://hdl.handle.net/2445/201449
Access Level:acceso abierto
Palabra clave:Cerebel
Síndrome de Down
Proteòmica
Cerebellum
Down syndrome
Proteomics
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spelling Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate geneOrtega, MireiaToma, Ilario deFernández Blanco, ÁlvaroCalderón, AnnaBarahona, LucíaTrullàs i Oliva, RamonSabidó, EduardDierssen, MaraCerebelSíndrome de DownProteòmicaCerebellumDown syndromeProteomicsDYRK1A 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.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.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.Frontiers2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/201449Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fnmol.2022.1015220Frontiers In Molecular Neuroscience, 2022, vol. 15, p. 1015220https://doi.org/10.3389/fnmol.2022.1015220cc by (c) Ortega, Mireia et al., 2022http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2014492026-05-27T06:46:51Z
dc.title.none.fl_str_mv Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene
title Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene
spellingShingle Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene
Ortega, Mireia
Cerebel
Síndrome de Down
Proteòmica
Cerebellum
Down syndrome
Proteomics
title_short Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene
title_full Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene
title_fullStr Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene
title_full_unstemmed Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene
title_sort Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene
dc.creator.none.fl_str_mv Ortega, Mireia
Toma, Ilario de
Fernández Blanco, Álvaro
Calderón, Anna
Barahona, Lucía
Trullàs i Oliva, Ramon
Sabidó, Eduard
Dierssen, Mara
author Ortega, Mireia
author_facet Ortega, Mireia
Toma, Ilario de
Fernández Blanco, Álvaro
Calderón, Anna
Barahona, Lucía
Trullàs i Oliva, Ramon
Sabidó, Eduard
Dierssen, Mara
author_role author
author2 Toma, Ilario de
Fernández Blanco, Álvaro
Calderón, Anna
Barahona, Lucía
Trullàs i Oliva, Ramon
Sabidó, Eduard
Dierssen, Mara
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cerebel
Síndrome de Down
Proteòmica
Cerebellum
Down syndrome
Proteomics
topic Cerebel
Síndrome de Down
Proteòmica
Cerebellum
Down syndrome
Proteomics
description 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.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.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.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/201449
url https://hdl.handle.net/2445/201449
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fnmol.2022.1015220
Frontiers In Molecular Neuroscience, 2022, vol. 15, p. 1015220
https://doi.org/10.3389/fnmol.2022.1015220
dc.rights.none.fl_str_mv cc by (c) Ortega, Mireia et al., 2022
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Ortega, Mireia et al., 2022
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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