PXD010689

PXD010689 is an original dataset announced via ProteomeXchange.

Title	Epigallocatechin-3-gallate restores hippocampal proteomic alterations driven by Dyrk1A overexpression in mice
Description	The inhibition of DYRK1A (Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase 1A) activity, triplicated in trisomy 21 subjects, has been proved as a promising therapy for Down syndrome. Epigallocatechin-3-gallate (EGCG), a polyphenol of green tea, is an allosteric inhibitor of DYRK1A that showed beneficial pro-cognitive effects in clinical trials with DS individuals. However, EGCG induces several pharmacological effects, and there is no proof that the observed improvements result from DYRK1A inhibition. Besides, the direct consequences of Dyrk1A overexpression are not well defined. We therefore used quantitative proteomics to decipher the proteome and phosphoproteome alterations resulting from Dyrk1A overexpression and its inhibition to get insight into the mechanism of action of EGCG. Towards this aim, we used mice overexpressing Dyrk1A, and compared the hippocampal proteome and phosphoproteome with their wild type counterparts, in basal conditions, and after treatment with EGCG. Moreover, given that the human clinical trials found that the effects of EGCG potentiated the effects of cognitive stimulation, we also included in our study treatment with environmental enrichment and its combination with EGCG. We found that DYRK1A overexpression leads to alterations in protein and phosphoprotein levels of hundreds of proteins, and that the levels of proteins involved in key postsynaptic pathways are restored by the cognitive enhancer treatments, which could help conceiving new therapeutic strategies.
HostingRepository	PRIDE
AnnounceDate	2019-12-11
AnnouncementXML	Submission_2019-12-11_04:21:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eduard Sabidó
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-08-06 03:37:04	ID requested
⏵ 1	2019-12-11 04:21:43	announced

De Toma I, Ortega M, Aloy P, Sabid, ó E, Dierssen M, DYRK1A Overexpression Alters Cognition and Neural-Related Proteomic Pathways in the Hippocampus That Are Rescued by Green Tea Extract and/or Environmental Enrichment. Front Mol Neurosci, 12():272(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: mouse, proteomics, dyrk1a, hippocampus, down syndrome

Eduard Sabidó
contact affiliation	Proteomics Unit, Center for Genomic Regulation, Barcelona Institute of Science and Technology, 08003 Barcelona. Proteomics Unit, Universitat Pompeu Fabra, 08003 Barcelona
contact email	eduard.sabido@crg.cat
lab head
Eduard Sabidó
contact affiliation	Centre de Regulació Genòmica
contact email	eduard.sabido@crg.cat
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010689
     1. Label: PRIDE project
     2. Name: Epigallocatechin-3-gallate restores hippocampal proteomic alterations driven by Dyrk1A overexpression in mice