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

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 Mao Q(10) MPP+ treatment caused 1 dose dependent loss of tyrosine hydroxylase and membrane potential and an Increase in caspase-3 activation in dopaminergic cells which were reversed by Mao 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 (C) 2010 Published by Elsevier Inc