Metallothionein in oxidative stress of Parkinson's disease

The loss of striatal dopaminergic neurons in Parkinson's disease results in enhanced turnover and metabolism of dopamine, augmenting the formation of H2O2 and generation of highly neurotoxic hydroxyl radicals (OH). In addition, the striatum of patients with Parkinson's disease has a low level of glutathione and complex I which may further predispose to oxidative stress. Neurotoxic agents causing Parkinson's disease, including 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,.3,6-tetrahydropyridine, generate free radicals and induce the levels of metallothionein isoforms. Moreover, metallothionein isoforms I and II are able to avert the neurotoxic effects of hydroxyl radicals, superoxide radicals, 1,1-diphenyl-2-picrylhydrazyl radicals, and the reactive oxygen species (containing singlet oxygen, superoxide and hydroxyl radicals) generated by photosensitized oxidation of riboflavin. The results of this investigation are interpreted to suggest that metallothionein isoforms, whose synthesis in the brain is induced by stress, cytokines and inflammatory processes, by being able to scavenge various free radicals, are capable of attenuating oxidative stress and of providing neuroprotection in drug-induced parkinsonism, and perhaps Parkinson's disease.