Model Studies Show MPP Is a Simple Member of a Large Group of Related Potent Dopaminergic Toxins.

Although the causes of Parkinson's disease (PD) are not fully understood, the consensus is that a combination of genetic and environmental factors plays a major role. The discovery that the synthetic chemical, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-derived -methyl-4-phenylpyridinium (MPP), recapitulates major pathophysiological characteristics of PD in humans and other mammals has provided the strongest support for this possibility; however, several key aspects of the mechanism remain unclear. In contrast to the widely accepted view that MPP is structurally unique and optimal for selective dopaminergic toxicity, previous studies have suggested that MPP is most likely a simple member of a large group of related dopaminergic toxins. Here we provide first evidence to support the above possibility using PD models. We also provide evidence to show that the inherent predisposition of dopaminergic neurons to produce high oxidative stress and related downstream effects when exposed to MPP and related mitochondrial toxins is responsible for their selective vulnerability to these toxins. More significantly, present findings suggest that if this broad group of MPP related dopaminergic toxins are present in work places or in the environment, they could cause far-reaching public health consequences.