SOD1 and amyotrophic lateral sclerosis: The up-regulation of PDI in the early symptomatic stages of ALS (Ahtoniemi et al., 2008) might be due to the attempt to resolve the misfolding and aggregating SOD1, but as the oxidative damage increases (Goldsteins et al., 2008) PDI becomes oxidized and loses its ability to function as a disulphide bond-rearranging enzyme (Figure 1).