SOD1related

SOD1‑related refers to biological and clinical aspects associated with the superoxide dismutase 1 (SOD1) gene and its protein product. SOD1 encodes a copper‑zinc enzyme that catalyzes the conversion of superoxide radicals to hydrogen peroxide and oxygen, a critical antioxidant defence in the cytoplasm of eukaryotic cells. The enzyme is ubiquitously expressed, and its activity protects tissues from oxidative stress‑induced damage.

Mutations in SOD1 were the first genetic cause identified for familial amyotrophic lateral sclerosis (ALS), accounting for approximately 20 % of familial cases and 2 % of apparently sporadic ALS. Over 180 pathogenic variants have been reported, most of which are missense substitutions that alter protein stability, promote aggregation, or confer a toxic gain of function. These mutant SOD1 proteins tend to form insoluble aggregates in motor neurons, contributing to neuronal degeneration through mechanisms that include mitochondrial dysfunction, impaired axonal transport, and activation of inflammatory pathways.

Beyond ALS, SOD1 dysfunction has been implicated in other neurodegenerative and cardiovascular conditions, although causal relationships remain less well defined. Experimental models, such as transgenic mice expressing human mutant SOD1, have been instrumental in elucidating disease mechanisms and testing therapeutic strategies. Approaches under investigation include antisense oligonucleotides to reduce mutant SOD1 expression, small molecules that stabilise the native protein conformation, and gene‑editing techniques aimed at correcting pathogenic variants.

Diagnostic testing for SOD1‑related ALS typically involves sequencing of the SOD1 coding region. Genetic counselling is recommended for affected individuals and their families, given the autosomal‑dominant inheritance pattern and variable penetrance observed in different mutations. Ongoing research continues to explore the broader role of SOD1 in oxidative stress biology and its potential as a therapeutic target across multiple disease contexts.