MECHANISMS OF MPTP TOXICITY

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces an experi mental model of Parkinson's disease (PD). It replicates most of the cl inical features of PD as well as the main biochemical and pathologic h allmarks of the disease. Although the MPTP model departs from PD in se veral aspects, it is thought that important insights into the neurodeg enerative process of PD may be obtained by elucidating the molecular m echanism of MPTP. In this article, we summarize the different steps of the complex metabolic pathway of MPTP and show how they may be implic ated in predisposing individuals to PD. We also outline findings perti nent to the mode of action of MPTP including overproduction of free ra dicals, implication of nitric oxide, nitration of tyrosine, impairment of mitochondrial respiration, and occurrence of apoptosis. All of the se factors map participate in the cascade of deleterious events that u ltimately lead to the death of dopaminergic neurons after MPTP adminis tration. Because of the similarity between PD and the MPTP model, we a re speculating that a similar scenario may underlie the neurodegenerat ive process in PD.