Abstract
Regional distribution of coenzyme Q
10 and mitochondrial complex-1 activity were estimated in the brains of control-(C57BL/6), metallothionein knock out-, metallothionein transgenic-, and homozygous weaver mutant mice; and human dopaminergic (SK-N-SH) cells with a primary objective to determine the neuroprotective potential of coenzyme Q
10 in Parkinson's disease. Complex-1 activity as well as coenzyme Q
10 were significantly higher in the cerebral cortex as compared to the striatum in all the genotypes examined. Complex-1 activity and coenzyme Q
10 were significantly reduced in weaver mutant mice and metallothionein knock out mice, but were significantly increased in metallothionein transgenic mice. The reduced complex-1 activity and
18F-DOPA uptake occurred concomitantly with negligible differences in the coenzyme Q
10 between in the cerebral cortex and striatum of weaver mutant mice. Administration of coenzyme Q
10 increased complex-1 activity and partially improved motoric performance in weaver mutant mice. Direct exposure of rotenone also reduced coenzyme Q
10, complex-1 activity, and mitochondrial membrane potential in SK-N-SH cells. Rotenone-induced down-regulation of complex-1 activity was attenuated by coenzyme Q
10 treatment, suggesting that complex-1 may be down regulated due to depletion of coenzyme Q
10 in the brain. Therefore, metallothionein-induced coenzyme Q
10 synthesis may provide neuroprotection by augmenting mitochondrial complex-1 activity in Parkinson's disease.