Superoxide dismutase 1 (SOD1) (SOD1)

Superoxide dismutase 1 (SOD1) is a critical antioxidant enzyme that catalyzes the dismutation of superoxide radicals into oxygen and hydrogen peroxide, protecting cells from oxidative damage (UniProt: P00441). The enzyme requires the binding of one copper ion and one zinc ion per subunit, as well as the formation of an intramolecular disulfide bond, to achieve its stable and active homodimeric form (PubMed: 12110171). In Amyotrophic Lateral Sclerosis (ALS), mutations in the SOD1 gene or failures in the copper-loading process lead to the formation of copper-deficient, misfolded SOD1 species that aggregate and exert neurotoxic effects (PubMed: 26109064). Therapeutic strategies such as activation via copper supply utilize small molecules like CuATSM to deliver copper directly to the SOD1 apoenzyme, promoting its maturation and stability while reducing the burden of toxic misfolded proteins (PubMed: 30635408). This approach aims to restore the essential antioxidant function of SOD1 and slow the progression of neurodegeneration in patients with SOD1-related pathologies.

Other names

SOD1Cu/Zn superoxide dismutaseSuperoxide dismutase [Cu-Zn]ALS1IPOAhSod1

Activation of the enzyme through the delivery of copper ions, which facilitates proper folding, disulfide bond formation, and dimerization, thereby restoring catalytic activity and reducing toxic aggregation.