SOD1 and amyotrophic lateral sclerosis: These observations, as a whole, are conceivable with the hypothesis, summarized in Figure 2, that the Ca2+-dependent excitotoxicity, associated with depolarization-dependent increase in SOD1 extracellular levels with consequent M1 receptor/SOD1 interaction, may be involved in the derangement of key neuro-modulatory networks during ALS pathogenesis.