While the potential risk of tumorigenesis linked to PPAR agonists remains a concern, the cumulative evidence suggests that modulation of the PGC-1α pathway, whether through direct overexpression or via upstream nuclear receptor activation, represents a multifaceted strategy to restore mitochondrial integrity, mitigate oxidative stress, and ultimately protect neurons in HD [130,131]. Here, PPARGC1A is linked to Huntington disease.