MPTP toxicity: implications for research in Parkinson's disease

In summary, the parkinsonism induced by MPTP in man closely resembles time-telescoped Parkinson's disease. Parkinsonian symptoms can be duplicated in all aspects under controlled conditions in subhuman primates; the biochemical changes are replicated in mice, dogs, and to varying degrees in other species. Mechanisms of bioactivation by MAO-B of MPTP to MPP+, concentration of MPP+ in neurons with a catecholamine uptake system, and vulnerability to cellular toxic effects of MPP+ are the basis for the specificity of MPTP targeting of nigrostriatal dopaminergic neurons. It is hoped that an understanding of the mechanism of species specificity and cellular toxicity will in time explain the pathogenesis of idiopathic Parkinson's disease and suggest new opportunities for effective therapy.