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...
| Authors: | ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2022 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/201449 |
| Online Access: | https://hdl.handle.net/2445/201449 |
| Access Level: | Open access |
| Keyword: | Cerebel Síndrome de Down Proteòmica Cerebellum Down syndrome Proteomics |
| _version_ | 1878735758737539072 |
|---|---|
| author | Ortega, Mireia |
| 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 |
| author_browse | Barahona, Lucía Calderón, Anna Dierssen, Mara Fernández Blanco, Álvaro Ortega, Mireia Sabidó, Eduard Toma, Ilario de Trullàs i Oliva, Ramon |
| 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 |
| collection | Dipòsit Digital de la UB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_82eca9daea2bcd8a5e5aba17ccf44a1f |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/201449 |
| publishDate | 2022 |
| publishDateSort | 2022 |
| publisher | Frontiers |
| publisherStr | Frontiers |
| reponame_str | Dipòsit Digital de la UB |
| spelling | Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene Ortega, Mireia Toma, Ilario de Fernández Blanco, Álvaro Calderón, Anna Barahona, Lucía Trullàs i Oliva, Ramon Sabidó, Eduard Dierssen, Mara Cerebel Síndrome de Down Proteòmica Cerebellum Down syndrome Proteomics 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. Frontiers https://hdl.handle.net/2445/201449 |
| 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 |
| status_str | publishedVersion |
| 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 | Cerebel Síndrome de Down Proteòmica Cerebellum Down syndrome Proteomics |
| topic_facet | Cerebel Síndrome de Down Proteòmica Cerebellum Down syndrome Proteomics |
| url | https://hdl.handle.net/2445/201449 |