In several species including human, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces clinical, biochemical and neuropathological changes similar to those, which occur in Parkinson’s disease. The dopamine transporter (DAT) is important to MPTP neurotoxicity because to be neurotoxin, an MPTP metabolite must first gain access to the dopaminergic neurons via DAT. Recent much evidence suggest that DAT is a mandatory factor for expression of MPTP neurotoxicity and may explain the selective neuronal damage in the substantia nigra against MPTP toxicity. In view of new insights, this article demonstrates that DAT plays an important role in the MPTP neurotoxic process and specific blockade of DAT with high-affinity inhibitors in neurodegenerative diseases such as Parkinson’s disease, where the effective levels of dopamine are marked reduced, may have beneficial consequences. Thus this review may provide valuable information for progressive neurodegeneration of the nigrostriatal dopaminergic neuronal pathway.
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