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Neurons in Vulnerable Regions of the Alzheimer’s Disease Brain Display Reduced ATM Signaling123
Ataxia telangiectasia (A-T) is a multisystemic disease caused by mutations in the ATM (A-T mutated) gene. It strikes before 5 years of age and leads to dysfunctions in many tissues, including the CNS, where it leads to neurodegeneration, primarily in cerebellum. Alzheimer’s disease (AD), by contrast...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Society for Neuroscience
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770009/ https://www.ncbi.nlm.nih.gov/pubmed/27022623 http://dx.doi.org/10.1523/ENEURO.0124-15.2016 |
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author | Shen, Xuting Chen, Jianmin Li, Jiali Kofler, Julia Herrup, Karl |
author_facet | Shen, Xuting Chen, Jianmin Li, Jiali Kofler, Julia Herrup, Karl |
author_sort | Shen, Xuting |
collection | PubMed |
description | Ataxia telangiectasia (A-T) is a multisystemic disease caused by mutations in the ATM (A-T mutated) gene. It strikes before 5 years of age and leads to dysfunctions in many tissues, including the CNS, where it leads to neurodegeneration, primarily in cerebellum. Alzheimer’s disease (AD), by contrast, is a largely sporadic neurodegenerative disorder that rarely strikes before the 7th decade of life with primary neuronal losses in hippocampus, frontal cortex, and certain subcortical nuclei. Despite these differences, we present data supporting the hypothesis that a failure of ATM signaling is involved in the neuronal death in individuals with AD. In both, partially ATM-deficient mice and AD mouse models, neurons show evidence for a loss of ATM. In human AD, three independent indices of reduced ATM function—nuclear translocation of histone deacetylase 4, trimethylation of histone H3, and the presence of cell cycle activity—appear coordinately in neurons in regions where degeneration is prevalent. These same neurons also show reduced ATM protein levels. And though they represent only a fraction of the total neurons in each affected region, their numbers significantly correlate with disease stage. This previously unknown role for the ATM kinase in AD pathogenesis suggests that the failure of ATM function may be an important contributor to the death of neurons in AD individuals. |
format | Online Article Text |
id | pubmed-4770009 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Society for Neuroscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-47700092016-03-28 Neurons in Vulnerable Regions of the Alzheimer’s Disease Brain Display Reduced ATM Signaling123 Shen, Xuting Chen, Jianmin Li, Jiali Kofler, Julia Herrup, Karl eNeuro New Research Ataxia telangiectasia (A-T) is a multisystemic disease caused by mutations in the ATM (A-T mutated) gene. It strikes before 5 years of age and leads to dysfunctions in many tissues, including the CNS, where it leads to neurodegeneration, primarily in cerebellum. Alzheimer’s disease (AD), by contrast, is a largely sporadic neurodegenerative disorder that rarely strikes before the 7th decade of life with primary neuronal losses in hippocampus, frontal cortex, and certain subcortical nuclei. Despite these differences, we present data supporting the hypothesis that a failure of ATM signaling is involved in the neuronal death in individuals with AD. In both, partially ATM-deficient mice and AD mouse models, neurons show evidence for a loss of ATM. In human AD, three independent indices of reduced ATM function—nuclear translocation of histone deacetylase 4, trimethylation of histone H3, and the presence of cell cycle activity—appear coordinately in neurons in regions where degeneration is prevalent. These same neurons also show reduced ATM protein levels. And though they represent only a fraction of the total neurons in each affected region, their numbers significantly correlate with disease stage. This previously unknown role for the ATM kinase in AD pathogenesis suggests that the failure of ATM function may be an important contributor to the death of neurons in AD individuals. Society for Neuroscience 2016-02-27 /pmc/articles/PMC4770009/ /pubmed/27022623 http://dx.doi.org/10.1523/ENEURO.0124-15.2016 Text en Copyright © 2016 Shen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | New Research Shen, Xuting Chen, Jianmin Li, Jiali Kofler, Julia Herrup, Karl Neurons in Vulnerable Regions of the Alzheimer’s Disease Brain Display Reduced ATM Signaling123 |
title | Neurons in Vulnerable Regions of the Alzheimer’s Disease Brain Display Reduced ATM Signaling123 |
title_full | Neurons in Vulnerable Regions of the Alzheimer’s Disease Brain Display Reduced ATM Signaling123 |
title_fullStr | Neurons in Vulnerable Regions of the Alzheimer’s Disease Brain Display Reduced ATM Signaling123 |
title_full_unstemmed | Neurons in Vulnerable Regions of the Alzheimer’s Disease Brain Display Reduced ATM Signaling123 |
title_short | Neurons in Vulnerable Regions of the Alzheimer’s Disease Brain Display Reduced ATM Signaling123 |
title_sort | neurons in vulnerable regions of the alzheimer’s disease brain display reduced atm signaling123 |
topic | New Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770009/ https://www.ncbi.nlm.nih.gov/pubmed/27022623 http://dx.doi.org/10.1523/ENEURO.0124-15.2016 |
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