Imperial College London
Alternate

ProfessorVictorTybulewicz

Faculty of Medicine, Department of Immunology and Inflammation

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3796 1612v.tybulewicz Website CV

 
 
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Location

 

L2-2720Francis Crick InstituteThe Francis Crick Institute

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Summary

 

Publications

Citation

BibTex format

@article{Granno:2019:10.1038/s41598-019-43820-4,
author = {Granno, S and Nixon-Abell, J and Berwick, DC and Tosh, J and Heaton, G and Almudimeegh, S and Nagda, Z and Rain, J-C and Zanda, M and Plagnol, V and Tybulewicz, VLJ and Cleverley, K and Wiseman, FK and Fisher, EMC and Harvey, K},
doi = {10.1038/s41598-019-43820-4},
journal = {Scientific Reports},
title = {Downregulated Wnt/β-catenin signalling in the Down syndrome hippocampus},
url = {http://dx.doi.org/10.1038/s41598-019-43820-4},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Granno,S
AU  - Nixon-Abell,J
AU  - Berwick,DC
AU  - Tosh,J
AU  - Heaton,G
AU  - Almudimeegh,S
AU  - Nagda,Z
AU  - Rain,J-C
AU  - Zanda,M
AU  - Plagnol,V
AU  - Tybulewicz,VLJ
AU  - Cleverley,K
AU  - Wiseman,FK
AU  - Fisher,EMC
AU  - Harvey,K
DO  - 10.1038/s41598-019-43820-4
PY  - 2019///
SN  - 2045-2322
TI  - Downregulated Wnt/β-catenin signalling in the Down syndrome hippocampus
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-019-43820-4
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31086297
UR  - http://hdl.handle.net/10044/1/71307
VL  - 9
ER  -
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