The ubiquitin–proteasome system and autophagy mutually interact in neurotoxin‐induced dopaminergic cell death models of Parkinson's disease
Hye Ji Jang, Kwang Chul Chung
Abstract
Precise control of the two major proteolysis systems [i.e. ubiquitin–proteasome system (UPS) and autophagy–lysosomal pathway (ALP)] is important for proper cell function. Here, we explored whether UPS and ALP affect each other in two neurotoxin‐based cell death models of Parkinson's disease. Monitoring UPS and ALP activity using their specific reporter plasmids revealed that treatment with the neurotoxin MPP + or the neurotoxin 6‐OHDA decreased proteasome activity in dopaminergic MN9D cells. Interestingly, ALP inhibition relieved or potentiated the decrease in proteasome activity induced by the two toxins. Moreover, suppression of proteasome activity promoted 6‐OHDA‐induced excessive autophagic flux, potentiating ALP dysregulation. In contrast, MPP + ‐induced impairment of ALP was alleviated by proteasome inhibition. These findings suggest a dynamic interplay between UPS and ALP operating in MN9D cells under two distinct toxin‐mediated cell death pathways.