Fig. 4.

Proposed mechanism of action for MPP⁺ cytotoxicity in HDNPCs. HDNPCs uptake the MPP⁺ through dopamine transporter (DAT). Once inside the cell, MPP⁺ may follow two routes: (1) interact/inhibit the activity or expression of TH, decreasing the levels of DA; or (2) concentrate in the mitochondria, potentially promoting the development of oxidative stress by reactive oxygen species (ROS) generation, which in turn could activate the autophagy response and protein aggregation leading to neuronal death. Illustration was done using the biomedical PowerPoint toolkit, biology bundle, Motifolio software (Motifolio Inc. Ellicott City, MD).