PPARGC1A and Parkinson disease: PD-associated mutations in the PARK2 gene lead to the loss of its E3 ligase function, resulting in ZNF746 accumulation in human PD brain.133 ZNF746 overexpression results in the loss of dopaminergic neurons in the substantia nigra by repressing the expression of peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1α (PPARGC1A)132 (Figure 5a).