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Altered regulation of tau phosphorylation in a mouse model of down syndrome aging
Down syndrome (DS) results from trisomy of human chromosome 21 (Hsa21) and is associated with an increased risk of Alzheimer's disease (AD). Here, using the unique transchromosomic Tc1 mouse model of DS we investigate the influence of trisomy of Hsa21 on the protein tau, which is hyperphosphory...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314962/ https://www.ncbi.nlm.nih.gov/pubmed/21843906 http://dx.doi.org/10.1016/j.neurobiolaging.2011.06.025 |
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author | Sheppard, Olivia Plattner, Florian Rubin, Anna Slender, Amy Linehan, Jacqueline M. Brandner, Sebastian Tybulewicz, Victor L.J. Fisher, Elizabeth M.C. Wiseman, Frances K. |
author_facet | Sheppard, Olivia Plattner, Florian Rubin, Anna Slender, Amy Linehan, Jacqueline M. Brandner, Sebastian Tybulewicz, Victor L.J. Fisher, Elizabeth M.C. Wiseman, Frances K. |
author_sort | Sheppard, Olivia |
collection | PubMed |
description | Down syndrome (DS) results from trisomy of human chromosome 21 (Hsa21) and is associated with an increased risk of Alzheimer's disease (AD). Here, using the unique transchromosomic Tc1 mouse model of DS we investigate the influence of trisomy of Hsa21 on the protein tau, which is hyperphosphorylated in Alzheimer's disease. We show that in old, but not young, Tc1 mice increased phosphorylation of tau occurs at a site suggested to be targeted by the Hsa21 encoded kinase, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A). We show that DYRK1A is upregulated in young and old Tc1 mice, but that young trisomic mice may be protected from accumulating aberrantly phosphorylated tau. We observe that the key tau kinase, glycogen synthase kinase3-β (GSK-3β) is aberrantly phosphorylated at an inhibitory site in the aged Tc1 brain which may reduce total glycogen synthase kinase3-β activity. It is possible that a similar mechanism may also occur in people with DS. |
format | Online Article Text |
id | pubmed-3314962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-33149622012-04-11 Altered regulation of tau phosphorylation in a mouse model of down syndrome aging Sheppard, Olivia Plattner, Florian Rubin, Anna Slender, Amy Linehan, Jacqueline M. Brandner, Sebastian Tybulewicz, Victor L.J. Fisher, Elizabeth M.C. Wiseman, Frances K. Neurobiol Aging Abstract of Online Article Down syndrome (DS) results from trisomy of human chromosome 21 (Hsa21) and is associated with an increased risk of Alzheimer's disease (AD). Here, using the unique transchromosomic Tc1 mouse model of DS we investigate the influence of trisomy of Hsa21 on the protein tau, which is hyperphosphorylated in Alzheimer's disease. We show that in old, but not young, Tc1 mice increased phosphorylation of tau occurs at a site suggested to be targeted by the Hsa21 encoded kinase, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A). We show that DYRK1A is upregulated in young and old Tc1 mice, but that young trisomic mice may be protected from accumulating aberrantly phosphorylated tau. We observe that the key tau kinase, glycogen synthase kinase3-β (GSK-3β) is aberrantly phosphorylated at an inhibitory site in the aged Tc1 brain which may reduce total glycogen synthase kinase3-β activity. It is possible that a similar mechanism may also occur in people with DS. Elsevier 2012-04 /pmc/articles/PMC3314962/ /pubmed/21843906 http://dx.doi.org/10.1016/j.neurobiolaging.2011.06.025 Text en © 2012 Elsevier Inc. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license |
spellingShingle | Abstract of Online Article Sheppard, Olivia Plattner, Florian Rubin, Anna Slender, Amy Linehan, Jacqueline M. Brandner, Sebastian Tybulewicz, Victor L.J. Fisher, Elizabeth M.C. Wiseman, Frances K. Altered regulation of tau phosphorylation in a mouse model of down syndrome aging |
title | Altered regulation of tau phosphorylation in a mouse model of down syndrome aging |
title_full | Altered regulation of tau phosphorylation in a mouse model of down syndrome aging |
title_fullStr | Altered regulation of tau phosphorylation in a mouse model of down syndrome aging |
title_full_unstemmed | Altered regulation of tau phosphorylation in a mouse model of down syndrome aging |
title_short | Altered regulation of tau phosphorylation in a mouse model of down syndrome aging |
title_sort | altered regulation of tau phosphorylation in a mouse model of down syndrome aging |
topic | Abstract of Online Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314962/ https://www.ncbi.nlm.nih.gov/pubmed/21843906 http://dx.doi.org/10.1016/j.neurobiolaging.2011.06.025 |
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