Copper is required for SOD activity180 and SOD1 mutant mice showed elevated concentrations of copper in the spinal cord during disease progression, suggesting that copper dyshomeostasis might facilitate the development of ALS.181 Overexpressing the copper chaperone CCS, which delivers copper to SOD1, led to an accelerated pathology and disease progression in the SOD1 G93A mice.182 Moreover, copper deficiency has been demonstrated to accelerate aberrant hydrophobicity of both wild-type and mutated SOD1 due to partial protein unfolding, which could be reverted by the addition of Cu2+. This evidence concerns the gene SOD1 and amyotrophic lateral sclerosis.