期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 14, 期 1-2, 页码 215-225出版社
WILEY
DOI: 10.1111/j.1582-4934.2008.00390.x
关键词
lipoic acid; acetyl-L-carnitine; mitochondrial dysfunction; oxidative damage; Parkinson's disease
资金
- National Institute on Aging [AG023265-01]
- Shanghai Science and Technical Committee [04DZ14007]
- Chinese Academy of Sciences [05PG14104]
- NATIONAL INSTITUTE ON AGING [R03AG023265] Funding Source: NIH RePORTER
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 1 alpha 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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