Proteasomal inhibition reduces parkin mRNA in PC12 and SH-SY5Y cells

Mutations in the gene encoding the E3 ubiquitin-protein ligase parkin have been shown to be a common genetic cause of familial early-onset Parkinson's disease (PD). In addition to its function in the ubiquitin-proteasome system (UPS), parkin has been ascribed general neuroprotective properties. Stress and mutation induced decreases in parkin solubility leading to compromised cytoprotection have recently been reported. We systematically investigated whether PD-related stresses including MG132 and epoxomicin (proteasomal impairment), tunicamycin (unfolded protein stress), and rotenone (mitochondrial dysfunction) r…