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Downregulated Wnt/β-catenin signalling in the Down syndrome hippocampus
- Source :
- Scientific Reports, Scientific Reports, Vol 9, Iss 1, Pp 1-20 (2019)
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
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.
- Subjects :
- Male
Chromosomes, Human, Pair 21
lcsh:Medicine
Down-Regulation
Protein Serine-Threonine Kinases
Hippocampus
Catechin
Article
Mice
Axin Protein
Alzheimer Disease
Animals
Humans
RNA-Seq
lcsh:Science
Wnt Signaling Pathway
Adaptor Proteins, Signal Transducing
Aged
lcsh:R
Developmental disorders
Middle Aged
Protein-Tyrosine Kinases
Alzheimer's disease
Disease Models, Animal
HEK293 Cells
lcsh:Q
Female
Down Syndrome
HeLa Cells
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports, Scientific Reports, Vol 9, Iss 1, Pp 1-20 (2019)
- Accession number :
- edsair.pmid.dedup....2c05d7ea7433957c2f504181d369d664