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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
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.
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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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