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Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of trinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HD involve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kina...

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Autores principales: Hua, Kuo-Feng, Chao, A-Ching, Lin, Ting-Yu, Chen, Wan-Tze, Lee, Yu-Chieh, Hsu, Wan-Han, Lee, Sheau-Long, Wang, Hsin-Min, Yang, Ding-I., Ju, Tz-Chuen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270658/
https://www.ncbi.nlm.nih.gov/pubmed/35818427
http://dx.doi.org/10.1016/j.jgr.2021.11.003
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author Hua, Kuo-Feng
Chao, A-Ching
Lin, Ting-Yu
Chen, Wan-Tze
Lee, Yu-Chieh
Hsu, Wan-Han
Lee, Sheau-Long
Wang, Hsin-Min
Yang, Ding-I.
Ju, Tz-Chuen
author_facet Hua, Kuo-Feng
Chao, A-Ching
Lin, Ting-Yu
Chen, Wan-Tze
Lee, Yu-Chieh
Hsu, Wan-Han
Lee, Sheau-Long
Wang, Hsin-Min
Yang, Ding-I.
Ju, Tz-Chuen
author_sort Hua, Kuo-Feng
collection PubMed
description BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of trinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HD involve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinase ataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM is involved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays a critical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expanded mutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effective component of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HD remains unclear and warrants further investigation. METHODS: This study used the R6/2 transgenic mouse model of HD and performed behavioral tests, survival rate, histological analyses, and immunoblot assays. RESULTS: The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK and reduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density and lifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2 protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. CONCLUSIONS: Thus, the oral administration of CK reduced the disease progression and markedly enhanced lifespan in the transgenic mouse model (R6/2) of HD.
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spelling pubmed-92706582022-07-10 Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway Hua, Kuo-Feng Chao, A-Ching Lin, Ting-Yu Chen, Wan-Tze Lee, Yu-Chieh Hsu, Wan-Han Lee, Sheau-Long Wang, Hsin-Min Yang, Ding-I. Ju, Tz-Chuen J Ginseng Res Research Article BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of trinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HD involve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinase ataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM is involved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays a critical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expanded mutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effective component of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HD remains unclear and warrants further investigation. METHODS: This study used the R6/2 transgenic mouse model of HD and performed behavioral tests, survival rate, histological analyses, and immunoblot assays. RESULTS: The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK and reduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density and lifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2 protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. CONCLUSIONS: Thus, the oral administration of CK reduced the disease progression and markedly enhanced lifespan in the transgenic mouse model (R6/2) of HD. Elsevier 2022-07 2021-11-11 /pmc/articles/PMC9270658/ /pubmed/35818427 http://dx.doi.org/10.1016/j.jgr.2021.11.003 Text en © 2021 The Korean Society of Ginseng. Publishing services by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Hua, Kuo-Feng
Chao, A-Ching
Lin, Ting-Yu
Chen, Wan-Tze
Lee, Yu-Chieh
Hsu, Wan-Han
Lee, Sheau-Long
Wang, Hsin-Min
Yang, Ding-I.
Ju, Tz-Chuen
Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway
title Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway
title_full Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway
title_fullStr Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway
title_full_unstemmed Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway
title_short Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway
title_sort ginsenoside compound k reduces the progression of huntington's disease via the inhibition of oxidative stress and overactivation of the atm/ampk pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270658/
https://www.ncbi.nlm.nih.gov/pubmed/35818427
http://dx.doi.org/10.1016/j.jgr.2021.11.003
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