Oxidative stress arises when reactive oxygen species (ROS) or nitrogen species (RNS) accumulate within cells. This can lead to oxidative modifications and altered functional states of proteins, nucleic acids and lipids. Oxidative stress is linked to neurodegeneration in ALS (Carrí et al., 2003) and oxidation products, such as malondialdehyde, hydroxynonenal, and oxidized proteins, DNA or membrane phospholipids, are elevated in SALS and FALS patients (Shaw et al., 1995; Beal et al., 1997; Ferrante et al., 1997; Bogdanov et al., 2000; Shibata et al., 2001) and mouse models of ALS (Gurney et al., 1994; Andrus et al., 1998; Bogdanov et al., 1998; Hall et al., 1998; Liu et al., 1998, 1999; Rizzardini et al., 2003). Mitochondria damage in ALS has also been attributed to intracellular oxidative stress (Fujita et al., 1996). The normal physiological function of SOD1 is the detoxification of superoxide radicals, although loss of SOD1 function is no longer favored as a disease mechanism in ALS (Saccon et al., 2013). However, mutations in SOD1 increase neuronal vulnerability to oxidative stress (Franco et al., 2013; Tsang et al., 2014). Moreover, in response to elevated ROS, SOD1 relocates from the cytoplasm to the nucleus, where it regulates the expression of oxidative resistance and repair genes (Tsang et al., 2014).