Superoxide dismutase [Cu-Zn] (SOD1) (SOD1)

Superoxide dismutase [Cu-Zn] (SOD1) is a vital antioxidant enzyme primarily located in the cytosol and mitochondrial intermembrane space, where it catalyzes the dismutation of toxic superoxide radicals into molecular oxygen and hydrogen peroxide [3, 18]. Beyond its canonical role in managing oxidative stress, SOD1 also functions as a nuclear transcription factor regulating stress response genes and exhibits antimicrobial properties [2, 15]. Mutations in the SOD1 gene are a major cause of familial amyotrophic lateral sclerosis (ALS), accounting for approximately 20% of cases [5, 20]. In ALS, the disease is driven by a toxic gain-of-function where mutant SOD1 proteins misfold and form aggregates that are lethal to motor neurons, rather than a simple loss of enzymatic activity [3, 24]. Therapeutic targeting of SOD1 focuses on reducing the burden of these toxic proteins. Tofersen (Qalsody) is an FDA-approved antisense oligonucleotide that triggers the degradation of SOD1 mRNA, thereby lowering protein levels in the central nervous system [1, 23]. Other emerging strategies include RNA interference (e.g., ARO-SOD1) and small molecules designed to stabilize the SOD1 dimer to prevent its dissociation into toxic monomers [1, 6]. Clinical monitoring of these therapies often utilizes neurofilament light chain (NfL) as a surrogate biomarker for neuronal preservation and efficacy [20, 24].

Other names

Superoxide dismutase 1Cu/Zn superoxide dismutaseAmyotrophic lateral sclerosis 1ALS1IPOAhSod1Indophenoloxidase ASoluble superoxide dismutase 1

Antisense oligonucleotide (ASO) mediated degradation of SOD1 mRNA to reduce protein synthesis; RNA interference (RNAi) for gene silencing; Small molecule stabilization of the SOD1 homodimer to prevent misfolding and aggregation.