PPARGC1A and amyotrophic lateral sclerosis: In fact PGC-1α is downregulated in ALS patients and it is known that silencing of PGC1α reduces the expression of SIRT3, which is the main mitochondrial deacetylase with a number of substrates (including SOD2), whose main function is to counteract ROS production and detoxification (Bause and Haigis, 2013), while overexpression of SIRT3 stimulates the expression of PGC1α causing a further decrease of ROS in a positive feedback loop (Kong et al., 2010).