• Open Access

Combined R-α–lipoic acid and acetyl-L-carnitine exerts efficient preventative effects in a cellular model of Parkinson’s disease

Authors

  • Hongyu Zhang,

    1. Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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    • Current address: Neuronal Survival Unit, Wallenberg Neuroscience Center, Lund University, BMC A10, 221 84 Lund, Sweden

  • Haiqun Jia,

    1. Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    2. Graduate School of the Chinese Academy of Sciences, Beijing, China
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  • Jianghai Liu,

    1. Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Ni Ao,

    1. Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Bing Yan,

    1. Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    2. Graduate School of the Chinese Academy of Sciences, Beijing, China
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  • Weili Shen,

    1. Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Xuemin Wang,

    1. Department of Biochemistry, Second Military Medical University, Shanghai, China
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  • Xin Li,

    1. Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Cheng Luo,

    1. Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Jiankang Liu

    Corresponding author
    1. Institute for Brain Aging and Dementia, University of California, Irvine, CA, USA
    2. Institute of Mitochondrial Biology and Medicine, Xi’an Jiaotong University School of Life Sciences and Technology, Xi’an, China
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Correspondence to: Jiankang LIU, Ph.D., Institute of Mitochondrial Biology and Medicine, Xi’an Jiaotong University School of Life Sciences and Technology, 28 West Xianning Road, Xi’an, China.
Tel.: +86-29-8266-7664
Fax: +86+29-8266-3876
E-mail: j.liu@mail.xjtu.edu.cn

Abstract

Mitochondrial dysfunction and oxidative damage are highly involved in the pathogenesis of Parkinson’s disease (PD). Some mitochondrial antioxidants/nutrients that can improve mitochondrial function and/or attenuate oxidative damage have been implicated in PD therapy. However, few studies have evaluated the preventative effects of a combination of mitochondrial antioxidants/nutrients against PD, and even fewer have sought to optimize the doses of the combined agents. The present study examined the preventative effects of two mitochondrial antioxidant/nutrients, R-α–lipoic acid (LA) and acetyl-L-carnitine (ALC), in a chronic rotenone-induced cellular model of PD. We demonstrated that 4-week pretreatment with LA and/or ALC effectively protected SK-N-MC human neuroblastoma cells against rotenone-induced mitochondrial dysfunction, oxidative damage and accumulation of α-synuclein and ubiquitin. Most notably, we found that when combined, LA and ALC worked at 100–1000-fold lower concentrations than they did individually. We also found that pretreatment with combined LA and ALC increased mitochondrial biogenesis and decreased production of reactive oxygen species through the up-regulation of the peroxisome proliferator-activated receptor-γ coactivator 1α as a possible underlying mechanism. This study provides important evidence that combining mitochondrial antioxidant/nutrients at optimal doses might be an effective and safe prevention strategy for PD.

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