Superoxide dismutase (SOD) catalyzes the conversion of superoxide radical to hydrogen peroxide. In the cytosol, the primary SOD isoform is SOD1 (Cu/Zn-SOD). Mutations in the SOD1 gene are associated with which neurodegenerative disease?

• A Familial amyotrophic lateral sclerosis (ALS) ✓
• B Alzheimer's disease
• C Huntington's disease
• D Parkinson's disease

Explanation

SOD1 mutations account for approximately 20% of familial ALS cases and about 2% of all ALS. The mutant SOD1 protein acquires a toxic gain-of-function (not simply loss of dismutase activity) that causes motor neuron death through mechanisms including protein aggregation, mitochondrial dysfunction, and ER stress. This connection between oxidative stress defense enzymes and neurodegeneration makes SOD1 a paradigmatic gene in ALS genetics. SOD2 (MnSOD) is the mitochondrial isoform; SOD3 is the extracellular isoform.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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