Rescue of a Rotenone Model of Parkinson’s Disease in C. elegans by the Mitochondrial Na+/Ca2+ Exchanger Inhibitor CGP37157

Abstract

We have previously shown that the compound CGP37157, a mitochondrial Na+/Ca2+ exchanger inhibitor, increases lifespan and improves muscle and mitochondrial structure during aging in wild-type C. elegans nematodes. We used here a rotenone model of Parkinson's disease in C. elegans to test the ability of CGP37157 to rescue the alterations induced by the toxicant. Rotenone, a mitochondrial respiratory chain complex I inhibitor, reduced worm lifespan and muscle activity, measured as worm mobility, pharyngeal pumping, and defecation rate. It also increased ROS production, decreased mitochondrial membrane potential, and disorganized mitochondrial structure. Moreover, it induced degeneration of dopaminergic neurons and changes in behavior. We found that CGP37157 produced a partial or complete reversal of most of these alterations. These results are consistent with our previous proposal that Ca2+ homeostasis is important in the development of neurodegenerative diseases, and modulation of the Ca2+ signaling toolkit may be a novel target for their treatment.