NOX2-TRPM2 coupling promotes Zn²⁺ inhibition of complex III to exacerbate ROS production in a cellular model of Parkinson's disease.

ABSTRACT: Reactive oxygen species (ROS) serve vital physiological functions, but aberrant ROS production contributes to numerous diseases. Unfortunately, therapeutic progress targeting pathogenic ROS has been hindered by the limited understanding of whether the mechanisms driving pathogenic ROS differ from those governing physiological ROS generation. To address this knowledge gap, we utilised a cellular model of Parkinson's disease (PD), as an exemplar of ROS-associated diseases. We exposed SH-SY5Y neuroblastoma cells to the PD-toxin, MPP⁺ (1-methyl-4-phenylpyridinium) and studied ROS upregulation leading to cell death, the primary cause of PD. We demonstrate: (1) MPP⁺ stimulates ROS production by raising cytoplasmic Ca²⁺ levels, rather than acting directly on mitoc

SUBMITTER: AlAhmad M 

PROVIDER: S-EPMC11310326 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature