Caenorhabditis elegans model studies show $MPP^+$is a simple member of a large group of related potent dopaminergic toxins
Murphy, David Patel, Harshil Wimalasena, Kandatege
Murphy, David
Patel, Harshil
Wimalasena, Kandatege
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2021-01-26
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Murphy, D., Patel, H., & Wimalasena, K. (2021). Caenorhabditis elegans model studies show MPP+Is a simple member of a large group of related potent dopaminergic toxins. Chemical Research in Toxicology, doi:10.1021/acs.chemrestox.0c00422
Abstract
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 N-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 in vitro studies have suggested that $MPP^+$ is most likely a simple member of a large group of related dopaminergic toxins. Here we provide first in vivo evidence to support the above possibility using Caenorhabditis elegans PD models. We also provide in vivo 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.
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American Chemical Society
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Chemical Research in Toxicology;
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0893-228X
1520-5010
1520-5010