Neuroprotection by a mitochondria-targeted drug in a Parkinson's disease model. Free Radic Biol Med 2010 Dec 01;49(11):1674-84
Date
09/11/2010Pubmed ID
20828611Pubmed Central ID
PMC4020411DOI
10.1016/j.freeradbiomed.2010.08.028Scopus ID
2-s2.0-78049357951 (requires institutional sign-in at Scopus site) 154 CitationsAbstract
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.
Author List
Ghosh A, Chandran K, Kalivendi SV, Joseph J, Antholine WE, Hillard CJ, Kanthasamy A, Kanthasamy A, Kalyanaraman BAuthors
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinBalaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimals
Cells, Cultured
Cytoprotection
Disease Models, Animal
Dopamine
Drug Delivery Systems
Drug Evaluation, Preclinical
Male
Mice
Mitochondria
Neurons
Neuroprotective Agents
Neurotoxins
Organophosphorus Compounds
Osmolar Concentration
Parkinsonian Disorders
Rats
Ubiquinone
