Combined R-alpha-lipoic acid and acetyl-L-carnitine exerts efficient preventative effects in a cellular model of Parkinson's disease.
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-alpha-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 alpha-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-gamma coactivator 1alpha 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.
Zhang
Hongyu
H
Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Jia
Haiqun
H
Liu
Jianghai
J
Ao
Ni
N
Yan
Bing
B
Shen
Weili
W
Wang
Xuemin
X
Li
Xin
X
Luo
Cheng
C
Liu
Jiankang
J
D000108:Acetylcarnitine / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism / Q000517:prevention & control*; D012402:Rotenone / Q000494:pharmacology; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use; D025801:Ubiquitin / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology; D051844:alpha-Synuclein / Q000378:metabolism
D000975:Antioxidants; D025801:Ubiquitin; D014475:Uncoupling Agents; D051844:alpha-Synuclein; D012402:Rotenone; D000108:Acetylcarnitine; D008063:Thioctic Acid