Open AccessCombined R‐α–lipoic acid and acetyl‐L‐carnitine exerts efficient preventative effects in a cellular model of Parkinson’s disease
Author(s) -
Zhang Hongyu,
Jia Haiqun,
Liu Jianghai,
Ao Ni,
Yan Bing,
Shen Weili,
Wang Xuemin,
Li Xin,
Luo Cheng,
Liu Jiankang
Publication year - 2010
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00390.x
Subject(s) - alpha lipoic acid , mitochondrial biogenesis , rotenone , reactive oxygen species , oxidative stress , mitochondrion , carnitine , parkinson's disease , pharmacology , antioxidant , ppargc1a , oxidative phosphorylation , lipoic acid , chemistry , biology , medicine , biochemistry , disease , coactivator , gene , transcription factor
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.