Caenorhabditis elegans Model Studies Show MPP+ Is a Simple Member of a Large Group of Related Potent Dopaminergic Toxins.
Chem Res Toxicol
; 34(5): 1275-1285, 2021 05 17.
Article
en En
| MEDLINE
| ID: mdl-33496570
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
1-Metil-4-fenilpiridinio
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Caenorhabditis elegans
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Neuronas Dopaminérgicas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Chem Res Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos