SOD1 (Superoxide Dismutase 1) Protein <table class="infobox infobox-protein">
Overview ...
SOD1 (Superoxide Dismutase 1) Protein <table class="infobox infobox-protein">
Overview SOD1 (Superoxide Dismutase 1) is a 154-amino acid copper/zinc-binding enzyme that catalyzes the dismutation of superoxide radical (O₂⁻) to hydrogen peroxide (H₂O₂) and molecular oxygen (O₂). This enzyme is a critical component of cellular antioxidant defense and is centrally implicated in the pathogenesis of familial amyotrophic lateral sclerosis (ALS). [@sodi]
Structure SOD1 is a homodimeric protein with each subunit containing: [@sodj]
One copper ion (catalytic core)
One zinc ion (structural stability)
One intracellular disulfide bond (Cys57-Cys146)
Structural Features
SOD1 adopts multiple conformational states: [@sodq]
Apo-state (metal-free)
Holo-state (fully loaded with Cu and Zn)
Partially metalated states
Mutant PRESENT states (ALS-associated)
Function
Enzymatic Activity SOD1 catalyzes the dismutation reaction:
2O₂⁻ + 2H⁺ → H₂O₂ + O₂
This reaction occurs through a cyclic mechanism involving:
Reduction of Cu²⁺ to Cu⁺ by superoxide
Oxidation of Cu⁺ back to Cu²⁺ by another superoxide
Release of hydrogen peroxide
Cellular Functions Beyond superoxide scavenging, SOD1 participates in:
Redox signaling
Iron metabolism
Mitochondrial function
Immune response
Cellular proteostasis
Role in ALS
Genetics Over 190 SOD1 mutations cause familial ALS, including:
A4V (most common in North America)
G93A (most studied experimental mutation)
H46R (common in Japan)
G86R (common in Sweden)
Pathogenic Mechanisms
Misfolding and Aggregation Mutant SOD1 forms toxic species:
Soluble oligomers
Insoluble aggregates
Sequestration of cellular proteins
Loss of Function Mutations disrupt:
Enzymatic activity
Dimer stability
Metal binding capacity
Gain of Toxic Function Mutant SOD1 acquires toxic properties:
Mitochondrial dysfunction
ER stress
Axonal transport defects
Glial cell activation
Works with Other ALS Genes SOD1 ALS shares pathways with:
TARDBP (TDP-43)
[FUS](/genes/fus)
[C9orf72](/genes/c9orf72)
UBQLN2
SOD1 in Other Diseases
Alzheimer's Disease
SOD1 activity altered in AD brain
may contribute to oxidative stress
Interaction with amyloid-β
Parkinson's Disease
Reduced SOD1 activity in PD brain
Associations with PINK1, Parkin pathways
Mitochondrial dysfunction
Other Conditions
Cancer (altered expression)
Diabetes (vascular complications)
Aging (oxidative stress)
Therapeutics
SOD1-Targeting Approaches
Gene Silencing
ASOs targeting SOD1 mRNA
siRNA delivery
CRISPR-based approaches
Small Molecules
Copper chelators
Protein aggregators
Antioxidants
Immunotherapy
Anti-SOD1 antibodies
Vaccine approaches
Clinical Trials
Biomarkers
SOD1 in CSF
Total SOD1 levels
Mutant-specific SOD1
Post-translational modifications
Imaging
PET ligands for SOD1 aggregates (experimental)
MR spectroscopy
Animal Models
Transgenic Models
SOD1 G93A mice (most common)
SOD1 G37R mice
SOD1 H46R mice
Phenotypes
Progressive motor neuron loss
Muscle denervation
Shorter lifespan
Glial activation
Diagnostics
Genetic Testing
Commercial panels available
Prenatal testing possible
Preimplantation genetic diagnosis
Biochemical Testing
SOD1 activity assays
Mutation analysis
Protein levels
See Also
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
External Links
[PubMed](https://pubmed.ncbi.nlm.nih.gov/)
[KEGG Pathways](https://www.genome.jp/kegg/pathway.html)
References
[Unknown, SOD1 structure and function (n.d.)](https://pubmed.ncbi.nlm.nih.gov/11004443/)
[Unknown, SOD1 mutations in ALS (n.d.)](https://pubmed.ncbi.nlm.nih.gov/21675965/)
[Unknown, SOD1 aggregation mechanisms (n.d.)](https://pubmed.ncbi.nlm.nih.gov/20192780/)
[Unknown, SOD1 animal models (n.d.)](https://pubmed.ncbi.nlm.nih.gov/16740650/)
[Unknown, SOD1 therapeutic approaches (n.d.)](https://pubmed.ncbi.nlm.nih.gov/26292750/)
[Unknown, SOD1 in sporadic ALS (n.d.)](https://pubmed.ncbi.nlm.nih.gov/12528827/)
[Unknown, Copper-zinc superoxide dismutase enzymology (n.d.)](https://pubmed.ncbi.nlm.nih.gov/10818043/)
[Unknown, SOD1 and oxidative stress in neurodegeneration (n.d.)](https://pubmed.ncbi.nlm.nih.gov/14637062/)
[Unknown, SOD1 genetics and pathogenesis (n.d.)](https://pubmed.ncbi.nlm.nih.gov/24270316/)
[Unknown, SOD1 clinical trials (n.d.)](https://pubmed.ncbi.nlm.nih.gov/28648975/)
[Unknown, SOD1 biomarker development (n.d.)](https://pubmed.ncbi.nlm.nih.gov/25962917/)
[Unknown, SOD1 and mitochondria (n.d.)](https://pubmed.ncbi.nlm.nih.gov/22276359/)
[Unknown, SOD1 in Alzheimer's disease (n.d.)](https://pubmed.ncbi.nlm.nih.gov/14637062/)
[Unknown, SOD1 in Parkinson's disease (n.d.)](https://pubmed.ncbi.nlm.nih.gov/20645434/)
[Unknown, Anti-SOD1 therapy approaches (n.d.)](https://pubmed.ncbi.nlm.nih.gov/28742137/)
[Unknown, SOD1 structural dynamics (n.d.)](https://pubmed.ncbi.nlm.nih.gov/24631664/)
[Unknown, SOD1 post-translational modifications (n.d.)](https://pubmed.ncbi.nlm.nih.gov/25088008/)
[Unknown, SOD1 oligomer toxicity (n.d.)](https://pubmed.ncbi.nlm.nih.gov/22593189/)
[Unknown, SOD1 and glia (n.d.)](https://pubmed.ncbi.nlm.nih.gov/25582528/)
[Unknown, SOD1 including familial and sporadic ALS (n.d.)](https://pubmed.ncbi.nlm.nih.gov/29678879/) Show full description