Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene.
DYRK1A
Down syndrome
cerebellum
mitochondria
oxidative phosphorylation system
proteomics
Journal
Frontiers in molecular neuroscience
ISSN: 1662-5099
Titre abrégé: Front Mol Neurosci
Pays: Switzerland
ID NLM: 101477914
Informations de publication
Date de publication:
2022
2022
Historique:
received:
09
08
2022
accepted:
02
12
2022
entrez:
2
1
2023
pubmed:
3
1
2023
medline:
3
1
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36590914
doi: 10.3389/fnmol.2022.1015220
pmc: PMC9800213
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1015220Informations de copyright
Copyright © 2022 De Toma, Ortega, Fernández-Blanco, Calderón, Barahona, Trullàs, Sabidó and Dierssen.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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