Neuroprotection by a mitochondria-targeted drug in a Parkinson's disease model

Free Radic Biol Med. 2010 Dec 1;49(11):1674-84. doi: 10.1016/j.freeradbiomed.2010.08.028. Epub 2010 Sep 7.


The objective of this study was to assess the neuroprotective effects of a mitochondria-targeted antioxidant, Mito-Q(10), the coenzyme-Q analog attached to a triphenylphosphonium cation that targets the antioxidant to mitochondria, in experimental models of Parkinson's disease (PD). Primary mesencephalic neuronal cells and cultured dopaminergic cells were treated with 1-methyl-4-phenylpyridinium (MPP(+)), an active metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and mice were used for testing the efficacy of Mito-Q(10). MPP(+) treatment caused a dose-dependent loss of tyrosine hydroxylase and membrane potential and an increase in caspase-3 activation in dopaminergic cells, which were reversed by Mito-Q(10). MPTP treatment induced a loss of striatal dopamine and its metabolites, inactivation of mitochondrial aconitase in the substantia nigra, and a loss of locomotor activity in mice. Treatment with Mito-Q(10) significantly inhibited both MPP(+)- and MPTP-induced neurotoxicity in cell culture and mouse models. Collectively, these results indicate that mitochondrial targeting of antioxidants is a promising neuroprotective strategy in this preclinical mouse model of PD.

Publication types

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

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Cells, Cultured
  • Cytoprotection / drug effects*
  • Disease Models, Animal
  • Dopamine / metabolism
  • Drug Delivery Systems / methods*
  • Drug Evaluation, Preclinical
  • Male
  • Mice
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / physiology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / pharmacology
  • Neurotoxins
  • Organophosphorus Compounds / administration & dosage*
  • Organophosphorus Compounds / pharmacology
  • Osmolar Concentration
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / pathology
  • Parkinsonian Disorders / prevention & control*
  • Rats
  • Ubiquinone / administration & dosage*
  • Ubiquinone / pharmacology


  • Neuroprotective Agents
  • Neurotoxins
  • Organophosphorus Compounds
  • Ubiquinone
  • mitoquinone
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Dopamine