Superoxide dismutase 1 aggregates (SOD1 aggregates) (SOD1 aggregates)

Superoxide dismutase 1 (SOD1) is a primary antioxidant enzyme that converts superoxide radicals into hydrogen peroxide and oxygen (UniProt P00441). In familial Amyotrophic Lateral Sclerosis (ALS), mutations in the SOD1 gene lead to the formation of misfolded protein species that assemble into toxic aggregates (PubMed: 29461114). These SOD1 aggregates are thought to exert a gain-of-toxic function, disrupting cellular processes such as mitochondrial activity, proteasomal degradation, and axonal transport within motor neurons (PubMed: 30271145). Therapeutic interventions like Tofersen, an antisense oligonucleotide, work by reducing the synthesis of SOD1 mRNA to decrease the overall protein load and subsequent aggregation (FDA, 2023). Other approaches include small molecules that stabilize the SOD1 dimer or antibodies designed to selectively clear misfolded SOD1 species (ClinicalTrials.gov: NCT05039099).

Other names

Misfolded SOD1SOD1 inclusionsMutant SOD1 aggregatesSuperoxide dismutase [Cu-Zn] aggregatesAmyotrophic lateral sclerosis 1 protein

Therapeutic strategies include the use of antisense oligonucleotides (ASOs) to degrade SOD1 mRNA and reduce protein expression, small molecule chaperones to stabilize the native SOD1 dimer, and monoclonal antibodies to target and clear extracellular misfolded SOD1 (PubMed: 33613465; FDA, 2023).