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KMID : 0352720220460040572
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Journal of Ginseng Research
2022 Volume.46 No. 4 p.572 ~ p.584
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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
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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
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Abstract
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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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KEYWORD
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AMP-Activated protein kinase, Ataxia-telangiectasia mutated, Panax ginseng, ginsenoside, Huntington's disease
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