Mitochondrial Dysfunction in Parkinson’s Disease
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders where oxidative stress and mitochondrial dysfunction have been implicated as etiological factors. Mitochondria are the major producers of reactive oxygen species (ROS) that can have damaging effects to cellular macromolecules leading to neurodegeneration. The most compelling evidence for the role of mitochondria in the pathogenesis of PD has been derived from toxicant-induced models of parkinsonism. Over the years, epidemiological studies have suggested a link between exposure to environmental toxins such as pesticides and the risk of developing PD. Data from human and experimental studies involving the use of chemical agents like paraquat, diquat, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone and maneb have provided valuable insight into the underlying mitochondrial mechanisms contributing to PD and associated neurodegeneration. In this review, we have discussed the role of mitochondrial ROS and dysfunction in the pathogenesis of PD with a special focus on environmental agent-induced parkinsonism. We have described the various mitochondrial mechanisms by which such chemicals exert neurotoxicity, highlighting some landmark epidemiological and experimental studies that support the role of mitochondrial ROS and oxidative stress in contributing to these effects. Finally, we have discussed the significance of these studies in understanding the mechanistic underpinnings of PD-related dopaminergic neurodegeneration.