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Deregulation of Protein Phosphatase 2A and Hyperphosphorylation of τ Protein Following Onset of Diabetes in NOD Mice
The histopathological hallmarks of Alzheimer disease (AD) include intraneuronal neurofibrillary tangles composed of abnormally hyperphosphorylated τ protein. Insulin dysfunction might influence AD pathology, as population-based and cohort studies have detected higher AD incidence rates in diabetic p...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554372/ https://www.ncbi.nlm.nih.gov/pubmed/22961084 http://dx.doi.org/10.2337/db12-0187 |
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author | Papon, Marie-Amélie El Khoury, Noura B. Marcouiller, François Julien, Carl Morin, Françoise Bretteville, Alexis Petry, Franck R. Gaudreau, Simon Amrani, Abdelaziz Mathews, Paul M. Hébert, Sébastien S. Planel, Emmanuel |
author_facet | Papon, Marie-Amélie El Khoury, Noura B. Marcouiller, François Julien, Carl Morin, Françoise Bretteville, Alexis Petry, Franck R. Gaudreau, Simon Amrani, Abdelaziz Mathews, Paul M. Hébert, Sébastien S. Planel, Emmanuel |
author_sort | Papon, Marie-Amélie |
collection | PubMed |
description | The histopathological hallmarks of Alzheimer disease (AD) include intraneuronal neurofibrillary tangles composed of abnormally hyperphosphorylated τ protein. Insulin dysfunction might influence AD pathology, as population-based and cohort studies have detected higher AD incidence rates in diabetic patients. But how diabetes affects τ pathology is not fully understood. In this study, we investigated the impact of insulin dysfunction on τ phosphorylation in a genetic model of spontaneous type 1 diabetes: the nonobese diabetic (NOD) mouse. Brains of young and adult female NOD mice were examined, but young NOD mice did not display τ hyperphosphorylation. τ phosphorylation at τ-1 and pS422 epitopes was slightly increased in nondiabetic adult NOD mice. At the onset of diabetes, τ was hyperphosphorylated at the τ-1, AT8, CP13, pS262, and pS422. A subpopulation of diabetic NOD mice became hypothermic, and τ hyperphosphorylation further extended to paired helical filament-1 and TG3 epitopes. Furthermore, elevated τ phosphorylation correlated with an inhibition of protein phosphatase 2A (PP2A) activity. Our data indicate that insulin dysfunction in NOD mice leads to AD-like τ hyperphosphorylation in the brain, with molecular mechanisms likely involving a deregulation of PP2A. This model may be a useful tool to address further mechanistic association between insulin dysfunction and AD pathology. |
format | Online Article Text |
id | pubmed-3554372 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-35543722014-02-01 Deregulation of Protein Phosphatase 2A and Hyperphosphorylation of τ Protein Following Onset of Diabetes in NOD Mice Papon, Marie-Amélie El Khoury, Noura B. Marcouiller, François Julien, Carl Morin, Françoise Bretteville, Alexis Petry, Franck R. Gaudreau, Simon Amrani, Abdelaziz Mathews, Paul M. Hébert, Sébastien S. Planel, Emmanuel Diabetes Original Research The histopathological hallmarks of Alzheimer disease (AD) include intraneuronal neurofibrillary tangles composed of abnormally hyperphosphorylated τ protein. Insulin dysfunction might influence AD pathology, as population-based and cohort studies have detected higher AD incidence rates in diabetic patients. But how diabetes affects τ pathology is not fully understood. In this study, we investigated the impact of insulin dysfunction on τ phosphorylation in a genetic model of spontaneous type 1 diabetes: the nonobese diabetic (NOD) mouse. Brains of young and adult female NOD mice were examined, but young NOD mice did not display τ hyperphosphorylation. τ phosphorylation at τ-1 and pS422 epitopes was slightly increased in nondiabetic adult NOD mice. At the onset of diabetes, τ was hyperphosphorylated at the τ-1, AT8, CP13, pS262, and pS422. A subpopulation of diabetic NOD mice became hypothermic, and τ hyperphosphorylation further extended to paired helical filament-1 and TG3 epitopes. Furthermore, elevated τ phosphorylation correlated with an inhibition of protein phosphatase 2A (PP2A) activity. Our data indicate that insulin dysfunction in NOD mice leads to AD-like τ hyperphosphorylation in the brain, with molecular mechanisms likely involving a deregulation of PP2A. This model may be a useful tool to address further mechanistic association between insulin dysfunction and AD pathology. American Diabetes Association 2013-02 2013-01-17 /pmc/articles/PMC3554372/ /pubmed/22961084 http://dx.doi.org/10.2337/db12-0187 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Research Papon, Marie-Amélie El Khoury, Noura B. Marcouiller, François Julien, Carl Morin, Françoise Bretteville, Alexis Petry, Franck R. Gaudreau, Simon Amrani, Abdelaziz Mathews, Paul M. Hébert, Sébastien S. Planel, Emmanuel Deregulation of Protein Phosphatase 2A and Hyperphosphorylation of τ Protein Following Onset of Diabetes in NOD Mice |
title | Deregulation of Protein Phosphatase 2A and Hyperphosphorylation of τ Protein Following Onset of Diabetes in NOD Mice |
title_full | Deregulation of Protein Phosphatase 2A and Hyperphosphorylation of τ Protein Following Onset of Diabetes in NOD Mice |
title_fullStr | Deregulation of Protein Phosphatase 2A and Hyperphosphorylation of τ Protein Following Onset of Diabetes in NOD Mice |
title_full_unstemmed | Deregulation of Protein Phosphatase 2A and Hyperphosphorylation of τ Protein Following Onset of Diabetes in NOD Mice |
title_short | Deregulation of Protein Phosphatase 2A and Hyperphosphorylation of τ Protein Following Onset of Diabetes in NOD Mice |
title_sort | deregulation of protein phosphatase 2a and hyperphosphorylation of τ protein following onset of diabetes in nod mice |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554372/ https://www.ncbi.nlm.nih.gov/pubmed/22961084 http://dx.doi.org/10.2337/db12-0187 |
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