SOD1 and amyotrophic lateral sclerosis: Consistent with this mechanism playing a key role in the pathology of ALS, astrocytes expressing mutant forms of SOD1 directly induce motor neuron death in co-culture systems in vitro, and this effect appears to be mediated by soluble factors or free radicals secreted by these reactive glial cells (Nagai et al., 2007; Bilsland et al., 2008).