disease 2,416 words KG: ent-dise-7094e623 2026-03-23
kind:diseasesection:diseasesstate:published
Contents

SOD1 Mutations in Amyotrophic Lateral Sclerosis

Disease Info
Antioxidant defenseCatalyzes the dismutation of superoxide radical (O₂⁻) to hydrogen peroxide (H₂O₂) and molecular oxygen (O₂)
Cellular protectionPrevents oxidative damage to proteins, lipids, and nucleic acids
Metal ion homeostasisRequires precise copper and zinc binding for proper folding and activity
Dimeric structureFunctions as a homodimer with each subunit requiring proper metalation
Intermediate speciesPartially folded monomers and small oligomers are highly toxic
Aggregate formationInsoluble aggregates accumulate in motor neurons and glia
SequestrationAggregates sequester essential cellular proteins including chaperones
Proteostasis overloadThe cellular protein quality control systems become overwhelmed
Direct mitochondrial bindingMutant SOD1 localizes to mitochondrial outer membranes
Electron transport chain impairmentComplex I and IV activities are reduced
Increased ROS productionParadoxically increases oxidative stress despite antioxidant enzyme activity
DatabasesOMIMOrphanetClinicalTrialsPubMed

Knowledge Graph

Related Hypotheses (28)

Selective Acid Sphingomyelinase Modulation Therapy
Score: 0.68
Dual-Domain Antibodies with Engineered Fc-FcRn Affinity Modu
Score: 0.57
Selective HDAC3 Inhibition with Cognitive Enhancement
Score: 0.56
Senescence-Induced Lipid Peroxidation Spreading
Score: 0.53
Circadian-Synchronized LRP1 Pathway Activation
Score: 0.53

Related Analyses (26)

CRISPR-based therapeutic approaches for neurodegenerative di
neurodegeneration · completed
TDP-43 phase separation therapeutics for ALS-FTD
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RNA binding protein dysregulation across ALS FTD and AD
neurodegeneration · archived
CRISPR-based therapeutic approaches for neurodegenerative di
neurodegeneration · archived
Microglial subtypes in neurodegeneration — friend vs foe
neuroscience · failed

Related Experiments (12)

s:** - Temporal analysis showing mitochondrial defects prece
falsification · proposed · Score: 0.40
s:** - Single-cell RNA-seq to measure editing efficiency acr
falsification · proposed · Score: 0.40
ALS Regional Onset and Spread: Network-Level Staging Model
clinical · proposed · Score: 0.40
ER-Golgi Secretory Pathway Dysfunction in PD - Experiment De
clinical · proposed · Score: 0.40
Viral and Post-Infectious Mechanisms in ALS — Experiment Des
clinical · proposed · Score: 0.40