The Open UniversitySkip to content
 

Downregulated Wnt/β-catenin signalling in the Down syndrome hippocampus

Granno, Simone; Nixon-Abell, Jonathon; Berwick, Daniel; Tosh, Justin; Heaton, George; Almudimeegh, Sultan; Nagda, Zenisha; Rain, Jean-Christophe; Zanda, Manuela; Plagnol, Vincent; Tybulewicz, Victor L. J.; Cleverley, Karen; Wiseman, Frances K.; Fisher, Elizabeth M. C. and Harvey, Kirsten (2019). Downregulated Wnt/β-catenin signalling in the Down syndrome hippocampus. Scientific Reports, 9, article no. 7322.

Full text available as:
[img]
Preview
PDF (Version of Record) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (6MB) | Preview
DOI (Digital Object Identifier) Link: https://doi.org/10.1038/s41598-019-43820-4
Google Scholar: Look up in Google Scholar

Abstract

Pathological mechanisms underlying Down syndrome (DS)/Trisomy 21, including dysregulation of essential signalling processes remain poorly understood. Combining bioinformatics with RNA and protein analysis, we identified downregulation of the Wnt/β-catenin pathway in the hippocampus of adult DS individuals with Alzheimer’s disease and the ‘Tc1’ DS mouse model. Providing a potential underlying molecular pathway, we demonstrate that the chromosome 21 kinase DYRK1A regulates Wnt signalling via a novel bimodal mechanism. Under basal conditions, DYRK1A is a negative regulator of Wnt/β-catenin. Following pathway activation, however, DYRK1A exerts the opposite effect, increasing signalling activity. In summary, we identified downregulation of hippocampal Wnt/β-catenin signalling in DS, possibly mediated by a dose dependent effect of the chromosome 21-encoded kinase DYRK1A. Overall, we propose that dosage imbalance of the Hsa21 gene DYRK1A affects downstream Wnt target genes. Therefore, modulation of Wnt signalling may open unexplored avenues for DS and Alzheimer’s disease treatment.

Item Type: Journal Item
Copyright Holders: 2019 The Authors
ISSN: 2045-2322
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 61480
Depositing User: ORO Import
Date Deposited: 28 May 2019 08:29
Last Modified: 29 May 2019 17:36
URI: http://oro.open.ac.uk/id/eprint/61480
Share this page:

Metrics

Altmetrics from Altmetric

Citations from Dimensions

Download history for this item

These details should be considered as only a guide to the number of downloads performed manually. Algorithmic methods have been applied in an attempt to remove automated downloads from the displayed statistics but no guarantee can be made as to the accuracy of the figures.

Actions (login may be required)

Policies | Disclaimer

© The Open University   contact the OU