Mutation in superoxide diamutasel (SOD1) is a cause of hereditary form of amyotrophic lateral sclerosis (ALS). Novel acquired toxicity (gain-of-function) is believed to play a crucial role. We propose that the nature of mutant SOD1 toxicity is disruption of intracellular Cu homeostasis. We provide evidences that copper transporters and chaperons are geared to accumulate Cu ion in the cells, and its excretion is downregulated with mutant SOD1 ("intracellular copper dysregulation" theory). Intracellular Cu modification using a Cu chelator and/or metallothionein resulted in a favorable outcome in an experimental study with a rodent model for hereditary form of ALS.
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