Of translational relevance, we demonstrated that forced/ectopic (re)expression of PGC-1α confers resistance to IR-enhanced ROS and SNCA expression, even in the presence of augmented PLK2 activity, thus suggesting the therapeutic exploitability of altered PGC-1α expression as an efficacious neuroprotective strategy in patients harboring IR with high risk of PD. This evidence concerns the gene PPARGC1A and Parkinson disease.