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

J Cell Mol Med. 2010 Jan;14(1-2):215-25. doi: 10.1111/j.1582-4934.2008.00390.x.

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-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcarnitine* / pharmacology
  • Acetylcarnitine* / therapeutic use
  • Antioxidants* / pharmacology
  • Antioxidants* / therapeutic use
  • Drug Synergism
  • Humans
  • Mitochondria* / drug effects
  • Mitochondria* / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Parkinson Disease / metabolism
  • Parkinson Disease / prevention & control*
  • Rotenone / pharmacology
  • Thioctic Acid* / pharmacology
  • Thioctic Acid* / therapeutic use
  • Ubiquitin / metabolism
  • Uncoupling Agents / pharmacology
  • alpha-Synuclein / metabolism

Substances

  • Antioxidants
  • Ubiquitin
  • Uncoupling Agents
  • alpha-Synuclein
  • Rotenone
  • Acetylcarnitine
  • Thioctic Acid