Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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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

  • Hua, Kuo-Feng (Department of Pathology, Tri-Service General Hospital, National Defense Medical Center) ;
  • Chao, A-Ching (Department of Neurology, Kaohsiung Medical University Hospital) ;
  • Lin, Ting-Yu (Department of Animal Science and Biotechnology, Tunghai University) ;
  • Chen, Wan-Tze (Institute of Brain Science and Brain Research Center, National Yang Ming Chiao Tung University) ;
  • Lee, Yu-Chieh (Wellhead Biological Technology Corp.) ;
  • Hsu, Wan-Han (Wellhead Biological Technology Corp.) ;
  • Lee, Sheau-Long (Wellhead Biological Technology Corp.) ;
  • Wang, Hsin-Min (6-Shun Clinic) ;
  • Yang, Ding-I. (Institute of Brain Science and Brain Research Center, National Yang Ming Chiao Tung University) ;
  • Ju, Tz-Chuen (Department of Animal Science and Biotechnology, Tunghai University)
  • Received : 2021.07.11
  • Accepted : 2021.11.04
  • Published : 2022.07.01
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Abstract

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.

Keywords

Acknowledgement

We are very grateful to Drs. Elena Cattaneo and Yijuang Chern for providing the striatal cell lines (STHdh Q7and STHdhQ109). We would like to thank National Laboratory Animal Center for providing the B6CBAFI/J mice.

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