PPARGC1A and Parkinson disease: In PD, downregulation may be a result of non-canonical PGC1α promoter methylation [18], and/or loss of antioxidant function due to lack of the E3 ubiquitin ligase Parkin leading to accumulation of Parkin-interacting substrate (PARIS; zinc finger protein 746, (ZNF746)), a transcriptional repressor of PGC1α [19].