Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene
IntroductionDYRK1A 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 n...
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.1015220/full |
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| author | Mireia Ortega Ilario De Toma Álvaro Fernández-Blanco Anna Calderón Lucía Barahona Ramón Trullàs Eduard Sabidó Eduard Sabidó Mara Dierssen Mara Dierssen Mara Dierssen |
| author_facet | Mireia Ortega Ilario De Toma Álvaro Fernández-Blanco Anna Calderón Lucía Barahona Ramón Trullàs Eduard Sabidó Eduard Sabidó Mara Dierssen Mara Dierssen Mara Dierssen |
| author_sort | Mireia Ortega |
| collection | DOAJ |
| description | IntroductionDYRK1A 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.MethodsTo 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 DiscussionOur 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. |
| first_indexed | 2024-04-11T12:59:41Z |
| format | Article |
| id | doaj.art-a94a519789dc467983ae50dd54cb6dfd |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-11T12:59:41Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-a94a519789dc467983ae50dd54cb6dfd2022-12-22T04:22:59ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-12-011510.3389/fnmol.2022.10152201015220Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate geneMireia Ortega0Ilario De Toma1Álvaro Fernández-Blanco2Anna Calderón3Lucía Barahona4Ramón Trullàs5Eduard Sabidó6Eduard Sabidó7Mara Dierssen8Mara Dierssen9Mara Dierssen10Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, SpainCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, SpainCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, SpainInstituto de Investigaciones Biomédicas de Barcelona, IIBB/CSIC y Centro de Investigación Biomédica en Red, Barcelona, SpainInstituto de Investigaciones Biomédicas de Barcelona, IIBB/CSIC y Centro de Investigación Biomédica en Red, Barcelona, SpainInstituto de Investigaciones Biomédicas de Barcelona, IIBB/CSIC y Centro de Investigación Biomédica en Red, Barcelona, SpainCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, SpainDepartment of Experimental Sciences, Universitat Pompeu Fabra (UPF), Barcelona, SpainCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, SpainDepartment of Experimental Sciences, Universitat Pompeu Fabra (UPF), Barcelona, SpainCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, SpainIntroductionDYRK1A 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.MethodsTo 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 DiscussionOur 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.https://www.frontiersin.org/articles/10.3389/fnmol.2022.1015220/fullDYRK1Acerebellummitochondriaoxidative phosphorylation systemDown syndromeproteomics |
| spellingShingle | Mireia Ortega Ilario De Toma Álvaro Fernández-Blanco Anna Calderón Lucía Barahona Ramón Trullàs Eduard Sabidó Eduard Sabidó Mara Dierssen Mara Dierssen Mara Dierssen Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene Frontiers in Molecular Neuroscience DYRK1A cerebellum mitochondria oxidative phosphorylation system Down syndrome proteomics |
| title | 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_short | 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 |
| topic | DYRK1A cerebellum mitochondria oxidative phosphorylation system Down syndrome proteomics |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.1015220/full |
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