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Nuclear translocation of AMPK-α1 potentiates striatal neurodegeneration in Huntington’s disease
Adenosine monophosphate–activated protein kinase (AMPK) is a major energy sensor that maintains cellular energy homeostasis. Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of CAG repeats in the huntingtin (Htt) gene. In this paper, we report that activation of the...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144412/ https://www.ncbi.nlm.nih.gov/pubmed/21768291 http://dx.doi.org/10.1083/jcb.201105010 |
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author | Ju, Tz-Chuen Chen, Hui-Mei Lin, Jiun-Tsai Chang, Ching-Pang Chang, Wei-Cheng Kang, Jheng-Jie Sun, Cheng-Pu Tao, Mi-Hua Tu, Pang-Hsien Chang, Chen Dickson, Dennis W. Chern, Yijuang |
author_facet | Ju, Tz-Chuen Chen, Hui-Mei Lin, Jiun-Tsai Chang, Ching-Pang Chang, Wei-Cheng Kang, Jheng-Jie Sun, Cheng-Pu Tao, Mi-Hua Tu, Pang-Hsien Chang, Chen Dickson, Dennis W. Chern, Yijuang |
author_sort | Ju, Tz-Chuen |
collection | PubMed |
description | Adenosine monophosphate–activated protein kinase (AMPK) is a major energy sensor that maintains cellular energy homeostasis. Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of CAG repeats in the huntingtin (Htt) gene. In this paper, we report that activation of the α1 isoform of AMPK (AMPK-α1) occurred in striatal neurons of humans and mice with HD. Overactivation of AMPK in the striatum caused brain atrophy, facilitated neuronal loss, and increased formation of Htt aggregates in a transgenic mouse model (R6/2) of HD. Such nuclear accumulation of AMPK-α1 was activity dependent. Prevention of nuclear translocation or inactivation of AMPK-α1 ameliorated cell death and down-regulation of Bcl2 caused by mutant Htt (mHtt). Conversely, enhanced expression of Bcl2 protected striatal cells from the toxicity evoked by mHtt and AMPK overactivation. These data demonstrate that aberrant activation of AMPK-α1 in the nuclei of striatal cells represents a new toxic pathway induced by mHtt. |
format | Online Article Text |
id | pubmed-3144412 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31444122012-01-25 Nuclear translocation of AMPK-α1 potentiates striatal neurodegeneration in Huntington’s disease Ju, Tz-Chuen Chen, Hui-Mei Lin, Jiun-Tsai Chang, Ching-Pang Chang, Wei-Cheng Kang, Jheng-Jie Sun, Cheng-Pu Tao, Mi-Hua Tu, Pang-Hsien Chang, Chen Dickson, Dennis W. Chern, Yijuang J Cell Biol Research Articles Adenosine monophosphate–activated protein kinase (AMPK) is a major energy sensor that maintains cellular energy homeostasis. Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of CAG repeats in the huntingtin (Htt) gene. In this paper, we report that activation of the α1 isoform of AMPK (AMPK-α1) occurred in striatal neurons of humans and mice with HD. Overactivation of AMPK in the striatum caused brain atrophy, facilitated neuronal loss, and increased formation of Htt aggregates in a transgenic mouse model (R6/2) of HD. Such nuclear accumulation of AMPK-α1 was activity dependent. Prevention of nuclear translocation or inactivation of AMPK-α1 ameliorated cell death and down-regulation of Bcl2 caused by mutant Htt (mHtt). Conversely, enhanced expression of Bcl2 protected striatal cells from the toxicity evoked by mHtt and AMPK overactivation. These data demonstrate that aberrant activation of AMPK-α1 in the nuclei of striatal cells represents a new toxic pathway induced by mHtt. The Rockefeller University Press 2011-07-25 /pmc/articles/PMC3144412/ /pubmed/21768291 http://dx.doi.org/10.1083/jcb.201105010 Text en © 2011 Ju et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Ju, Tz-Chuen Chen, Hui-Mei Lin, Jiun-Tsai Chang, Ching-Pang Chang, Wei-Cheng Kang, Jheng-Jie Sun, Cheng-Pu Tao, Mi-Hua Tu, Pang-Hsien Chang, Chen Dickson, Dennis W. Chern, Yijuang Nuclear translocation of AMPK-α1 potentiates striatal neurodegeneration in Huntington’s disease |
title | Nuclear translocation of AMPK-α1 potentiates striatal neurodegeneration in Huntington’s disease |
title_full | Nuclear translocation of AMPK-α1 potentiates striatal neurodegeneration in Huntington’s disease |
title_fullStr | Nuclear translocation of AMPK-α1 potentiates striatal neurodegeneration in Huntington’s disease |
title_full_unstemmed | Nuclear translocation of AMPK-α1 potentiates striatal neurodegeneration in Huntington’s disease |
title_short | Nuclear translocation of AMPK-α1 potentiates striatal neurodegeneration in Huntington’s disease |
title_sort | nuclear translocation of ampk-α1 potentiates striatal neurodegeneration in huntington’s disease |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144412/ https://www.ncbi.nlm.nih.gov/pubmed/21768291 http://dx.doi.org/10.1083/jcb.201105010 |
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