Affinage

SOD1

Superoxide dismutase [Cu-Zn] · UniProt P00441

Length
154 aa
Mass
15.9 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SOD1 is a copper- and zinc-dependent cytoplasmic homodimer that catalyzes the dismutation of superoxide to oxygen and hydrogen peroxide, serving both as a core antioxidant enzyme and as a generator of H2O2 used in redox signaling (PMID:12126755). Beyond detoxification, SOD1-derived H2O2 functions as a second messenger that reroutes metabolism and signaling: it oxidatively inactivates GAPDH to divert carbohydrate flux into the oxidative pentose phosphate pathway for NADPH production (PMID:34969852), stabilizes casein kinase 1-gamma (CK1γ/Yck1/2) to repress respiration in response to oxygen and glucose (PMID:23332757) and to sustain canonical Wnt signaling and proliferation (PMID:33218686). This signaling output is gated by nutrient sensing through mTORC1-mediated phosphorylation at T40, which tunes SOD1 activity to moderate ROS and prevent oxidative DNA damage (PMID:29727620). SOD1 also acts as an H2S oxidase, converting sulfide to sulfate or to per/polysulfides depending on sulfide levels and protecting cells from H2S toxicity (PMID:36630448). Enzymatic competence requires maturation by the copper chaperone CCS, which recognizes immature SOD1, transfers copper, and drives disulfide formation (PMID:30735496); metal loading and activity are additionally modulated by SIRT5-mediated desuccinylation (PMID:24140062) and by alternative copper delivery via DJ-1 (PMID:24567322). At the organismal level SOD1 governs hepatic gluconeogenic, glycolytic, and lipogenic metabolism (PMID:22974764) and protects neuromuscular integrity, with neuronal SOD1 being sufficient to prevent muscle mitochondrial dysfunction and neuromuscular junction denervation in a non-cell-autonomous manner (PMID:33561489). ALS-linked mutant SOD1 acquires toxic gain-of-function properties: metal-free oligomerization through cysteine oxidation (PMID:18301754), formation of a cytotoxic nonnative trimer (PMID:29666246), association with the cytoplasmic face of mitochondria with impaired protein import (PMID:21078990), nuclear exclusion that elevates oxidative DNA damage (PMID:17504823), and aberrant RNA-independent binding to G3BP1 that delays stress granule assembly (PMID:27481264); such misfolded species are selectively cleared by the E3 ligases Dorfin and the ERAD ligase gp78 (PMID:12145308, PMID:19661182). A homozygous in-frame SOD1 deletion causing complete loss of enzymatic activity produces an infantile progressive motor-neurological syndrome, establishing a loss-of-function disease mechanism distinct from the toxic gain-of-function of ALS mutants (PMID:34788402).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 2002 High

    Established the foundational identity of SOD1 as a metal-dependent enzyme, defining the catalytic activity and localization on which all later signaling and disease work builds.

    Evidence Biochemical enzymatic assay, metal cofactor identification, and subcellular fractionation

    PMID:12126755

    Open questions at the time
    • Does not address non-canonical signaling or substrate roles
    • No structural mechanism of catalysis defined here
  2. 2002 Medium

    Addressed how cells handle toxic mutant SOD1 by identifying Dorfin as an E3 ligase selectively ubiquitylating mutant but not wild-type SOD1, framing proteostatic clearance as a protective axis.

    Evidence Co-IP, ubiquitylation and proteasome assays in neural cells

    PMID:12145308

    Open questions at the time
    • Selectivity determinants for mutant SOD1 not defined
    • In vivo relevance to ALS not established
  3. 2007 Medium

    Showed that nuclear localization of SOD1 is protective and that mutant SOD1 nuclear exclusion increases oxidative DNA damage, linking SOD1 subcellular distribution to genome protection.

    Evidence Immunofluorescence, subcellular fractionation, and comet assay in transgenic mice and NSC34 cells

    PMID:17504823

    Open questions at the time
    • Mechanism of nuclear import/exclusion unresolved
    • Whether DNA damage drives motor neuron death not shown
  4. 2008 Medium

    Defined a shared biophysical route to toxic species, showing that demetallated SOD1 oligomerizes via free-cysteine oxidation across many ALS mutants.

    Evidence CD, thioflavin T fluorescence, size-exclusion chromatography, light scattering

    PMID:18301754

    Open questions at the time
    • No mutagenesis to directly confirm cysteine roles
    • Link between in vitro oligomers and cellular toxicity not made
  5. 2009 Medium

    Extended SOD1 quality control by showing the ERAD ligase gp78 degrades both wild-type and mutant SOD1 and reduces aggregation, identifying a second clearance pathway.

    Evidence Co-IP, ubiquitination, stability and viability assays with knockdown/overexpression

    PMID:19661182

    Open questions at the time
    • Relative contribution vs. other ligases unknown
    • ER-association of SOD1 substrate pool not defined
  6. 2010 High

    Identified a tissue-selective toxic mechanism whereby misfolded mutant SOD1 binds spinal cord mitochondria and impairs protein import, connecting SOD1 misfolding to mitochondrial dysfunction.

    Evidence Mitochondrial fractionation, LC-MS/MS proteomics, direct in vitro import assay

    PMID:21078990

    Open questions at the time
    • Import machinery component targeted not identified
    • Why spinal cord mitochondria are selectively vulnerable unclear
  7. 2011 Medium

    Placed SOD1 genetically in an ALS pathway independent of FUS and TARDBP, indicating mechanistic divergence among ALS genes.

    Evidence Zebrafish epistasis with mutant/wild-type allele combinations

    PMID:21829392

    Open questions at the time
    • Molecular basis of pathway independence not defined
    • Model-organism context limits direct human inference
  8. 2011 Medium

    Offered a membrane-toxicity mechanism by showing mutant A4V SOD1 forms pore-like structures causing membrane depolarization and calcium influx.

    Evidence AFM, bilayer electrophysiology, calcium imaging in neuroblastoma cells

    PMID:21930207

    Open questions at the time
    • In vivo occurrence of pores not demonstrated
    • Relation to oligomer/trimer species unclear
  9. 2012 Medium

    Demonstrated a systemic metabolic role by showing Sod1 knockout disrupts hepatic gluconeogenesis, glycolysis, and lipogenesis.

    Evidence Sod1 knockout mice, pyruvate tolerance test, enzyme activity assays

    PMID:22974764

    Open questions at the time
    • Direct redox targets among metabolic enzymes not identified
    • Whether effects are cell-autonomous in liver unknown
  10. 2013 High

    Reframed SOD1 as a redox signaling hub by showing its H2O2 product stabilizes CK1γ homologs to repress respiration in response to oxygen and glucose.

    Evidence Yeast epistasis, co-IP, in vitro binding, enzymatic assays, mammalian validation

    PMID:23332757

    Open questions at the time
    • Precise redox-sensitive residue on CK1γ not pinpointed
    • Generality across cell types incompletely mapped
  11. 2013 Medium

    Identified succinylation/desuccinylation by SIRT5 as a post-translational switch controlling SOD1 dismutase activity.

    Evidence Co-IP, in vitro desuccinylation, activity assays, site mutagenesis

    PMID:24140062

    Open questions at the time
    • Physiological conditions driving succinylation unknown
    • Single-lab finding without in vivo confirmation
  12. 2014 Medium

    Proposed an alternative copper-delivery route by showing DJ-1 binds copper at Cys-106 and transfers it to activate SOD1.

    Evidence X-ray crystallography of copper site, fluorescence kinetics, activity assays

    PMID:24567322

    Open questions at the time
    • Relative contribution vs. CCS in vivo not established
    • Cellular conditions favoring DJ-1 route unknown
  13. 2014 Low

    Linked a species-specific SOD1-PCBP1 interaction to nuclear accumulation of mutant SOD1 in transgenic pigs.

    Evidence Co-IP from pig and mouse brain, immunofluorescence, ubiquitin staining

    PMID:24577199

    Open questions at the time
    • Single tissue co-IP without functional validation of PCBP1 binding
    • Human relevance untested
  14. 2015 Medium

    Connected SOD1 to alpha-synuclein, showing direct interaction that accelerates SOD1 oligomerization independent of dismutase activity.

    Evidence BiFC, co-IP, oligomerization assays in cells, erythrocytes, and brain

    PMID:26643113

    Open questions at the time
    • Structural interface not resolved
    • In vivo pathological consequence not established
  15. 2016 Medium

    Defined a toxic protein-interaction mechanism whereby mutant SOD1 binds G3BP1 via its RRM domain and delays stress granule assembly.

    Evidence Co-IP, domain mapping by mutagenesis, stress granule dynamics, motor neuron co-localization

    PMID:27481264

    Open questions at the time
    • Consequence of delayed granule formation for neuron survival unclear
    • Reciprocal validation limited to single lab
  16. 2016 Medium

    Clarified maturation failure by showing ALS-associated hCCS mutations abrogate zinc binding, destabilizing the zinc-dependent hCCS-SOD1 heterodimer.

    Evidence Chromatographic SAXS and biochemical zinc/binding assays

    PMID:27282955

    Open questions at the time
    • Downstream effect on SOD1 maturation in vivo not shown
    • Disease causality of CCS variants not established here
  17. 2017 Medium

    Demonstrated that muscle-autonomous mutant SOD1 dismantles the NMJ through PKCθ-dependent redox perturbation, implicating non-neuronal SOD1 toxicity.

    Evidence Muscle-specific SOD1G93A transgenic mice, AChR turnover, PKCθ activity and inhibition

    PMID:28931313

    Open questions at the time
    • Redox target upstream of PKCθ not identified
    • Relative weight of muscle vs. neuronal contributions in ALS unclear
  18. 2018 High

    Resolved a key disease question by integrating mTORC1 phosphorylation (S39/T40) as a nutrient-responsive switch tuning SOD1 activity to limit oxidative DNA damage.

    Evidence In vitro kinase assay, mutagenesis, ROS and DNA damage assays, conservation analysis

    PMID:29727620

    Open questions at the time
    • Phosphatase counteracting T40 not identified
    • Quantitative impact on catalytic cycle not defined
  19. 2018 Medium

    Identified the cytotoxic conformer in ALS as a nonnative trimer rather than large aggregates, refining the toxic-species model.

    Evidence Structure-guided engineering, gel filtration, EM, viability assays

    PMID:29666246

    Open questions at the time
    • In vivo abundance of trimers not quantified
    • Mechanism by which trimers kill neurons unresolved
  20. 2019 High

    Provided a structural mechanism for SOD1 maturation, resolving stepwise CCS-mediated recognition, copper transfer, and disulfide formation.

    Evidence X-ray crystallography of precursors, intermediates, products plus biochemical validation

    PMID:30735496

    Open questions at the time
    • Timing of in vivo maturation flux not measured
    • Interplay with alternative chaperones unaddressed
  21. 2020 Medium

    Extended the SOD1-CK1γ axis to humans, showing SOD1-derived H2O2 stabilizes CK1γ to support canonical Wnt signaling and proliferation.

    Evidence SOD1 knockdown, CK1γ measurement, Wnt reporter and proliferation assays in HEK293

    PMID:33218686

    Open questions at the time
    • Direct oxidative modification site on CK1γ not defined
    • Tissue contexts where this operates not mapped
  22. 2021 High

    Established that neuronal SOD1 acts non-cell-autonomously to protect muscle, with neuronal rescue preventing muscle mitochondrial dysfunction and NMJ denervation.

    Evidence Neuron-specific transgenic rescue in Sod1-/- mice, mitochondrial ROS, oxygen consumption, calcium and NMJ analyses

    PMID:33561489

    Open questions at the time
    • Signal transmitted from neuron to muscle not identified
    • Applicability to gain-of-function ALS mutants unclear
  23. 2022 High

    Defined a major metabolic output of SOD1, showing its H2O2 inactivates GAPDH to redirect flux into the oxPPP for NADPH generation.

    Evidence Yeast and mammalian knockouts, flux measurements, proteomics, GAPDH activity assays

    PMID:34969852

    Open questions at the time
    • Spatial coupling of SOD1 and GAPDH not resolved
    • Quantitative share of NADPH supply via this route unclear
  24. 2022 Medium

    Demonstrated a loss-of-function human disease mechanism: complete SOD1 deficiency causes an infantile progressive motor-neurological syndrome, distinct from ALS gain-of-function.

    Evidence Exome sequencing, cDNA analysis, erythrocyte activity assays, protein quantification

    PMID:34788402

    Open questions at the time
    • Cellular basis of motor neuron vulnerability to deficiency unclear
    • Single patient/family study
  25. 2023 High

    Expanded SOD1's catalytic repertoire by identifying it as an H2S oxidase essential for sulfide detoxification.

    Evidence Knockout and overexpression in yeast and human cells, H2S oxidation and ROS assays

    PMID:36630448

    Open questions at the time
    • Active-site basis for sulfide vs. superoxide handling not resolved
    • Physiological sulfide sources targeted not defined
  26. 2024 Medium

    Identified the route of SOD1 secretion, showing Plekhg5 sequesters Sod1 into autophagosomal carriers that fuse with LROs for Rab26-dependent exocytosis at presynaptic terminals.

    Evidence Plekhg5 knockout mice, live imaging, co-localization, iPSC motoneurons, secretion assays

    PMID:39366938

    Open questions at the time
    • Extracellular function of secreted SOD1 not defined
    • Whether secretion mitigates or spreads mutant SOD1 toxicity unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how SOD1's redox-signaling outputs, its H2S oxidase activity, and its propensity to misfold are mechanistically integrated, and which specific molecular events convert SOD1 dysfunction into selective motor neuron death.
  • No unified model linking toxic conformers to defined cellular death pathway
  • Direct in vivo redox targets of SOD1-derived H2O2 incompletely catalogued
  • Relationship between secretion and disease spread untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 3 GO:0016209 antioxidant activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1 GO:0005739 mitochondrion 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-1430728 Metabolism 2 R-HSA-162582 Signal Transduction 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
CCSCK1ΓDJ-1G3BP1GP78PLEKHG5SIRT5SNCA

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 SOD1 (CuZn-SOD) is a copper- and zinc-containing homodimer that catalyzes the dismutation of superoxide anions to oxygen and hydrogen peroxide, and is found almost exclusively in intracellular cytoplasmic spaces. Biochemical characterization, enzymatic assay, subcellular fractionation Free radical biology & medicine High 12126755
2013 SIRT5 binds to SOD1, desuccinylates it, and thereby activates its enzymatic activity; succinylation of SOD1 decreases its dismutase activity, establishing succinylation/desuccinylation as a post-translational regulatory mechanism for SOD1. Co-immunoprecipitation, in vitro desuccinylation assay, enzymatic activity assay, site-directed mutagenesis of succinylation site Biochemical and biophysical research communications Medium 24140062
2013 In yeast and mammalian cells, SOD1 transmits signals from oxygen and glucose to repress respiration by stabilizing casein kinase 1-gamma (CK1γ) homologs (Yck1p/Yck2p); SOD1 binds a C-terminal degron in Yck1p/Yck2p and promotes kinase stability by catalyzing superoxide conversion to peroxide, which is required for respiratory repression. Genetic epistasis in yeast, co-immunoprecipitation, in vitro binding assay, enzymatic activity assays, mammalian cell line validation Cell High 23332757
2018 mTORC1 phosphorylates SOD1 at S39 (yeast) / T40 (human) in response to nutrients, which reversibly modulates SOD1 activity, moderates ROS levels, and prevents oxidative DNA damage; this is a conserved nutrient-sensing redox regulatory mechanism. In vitro kinase assay, site-directed mutagenesis, ROS measurement, DNA damage assay, conservation analysis across species Molecular cell High 29727620
2022 SOD1 integrates oxygen availability to regulate NADPH production: Sod1-derived H2O2 oxidatively inactivates the glycolytic enzyme GAPDH, which reroutes carbohydrate flux to the oxidative pentose phosphate pathway (oxPPP) to generate NADPH; this mechanism requires the bulk of cellular Sod1. Genetic knockout in yeast and mammalian cells, biochemical flux measurements, mass spectrometry proteomics, GAPDH activity assays Proceedings of the National Academy of Sciences of the United States of America High 34969852
2002 Dorfin, a RING finger E3 ubiquitin ligase, physically binds and ubiquitylates ALS-linked mutant SOD1 proteins (but not wild-type SOD1), targeting them for proteasomal degradation and reducing SOD1 inclusions; Dorfin overexpression protects neural cells from mutant SOD1 toxicity. Co-immunoprecipitation, ubiquitylation assay, proteasome inhibition, cell viability assay, immunohistochemistry The Journal of biological chemistry Medium 12145308
2009 The ER-resident E3 ubiquitin ligase gp78 interacts with SOD1 (both wild-type and mutant), promotes its ubiquitination and proteasomal degradation via ER-associated degradation (ERAD), and reduces mutant SOD1 aggregate formation and cell death. Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression with stability measurements, cell viability assay Human molecular genetics Medium 19661182
2019 Human CCS (hCCS) catalyzes SOD1 maturation through a stepwise mechanism involving: molecular recognition of immature SOD1 driven by interface interactions, induced-fit complexation stabilizing the SOD1 disulphide sub-loop, copper transfer to the SOD1 active site, and delayed disulphide formation; a single destabilizing substitution in hCCS reduces homodimer affinity to create a pool available for SOD1 interaction. X-ray crystallography of reaction precursors, intermediates, and products; biochemical assays for copper transfer and SOD1 activation PLoS biology High 30735496
2016 A faulty interaction between ALS-associated hCCS mutations and SOD1 occurs because the hCCS mutation abrogates zinc binding, which inhibits hCCS-SOD1 heterodimer formation; SOD1 zinc loss also disrupts the hCCS-SOD1 interaction, showing mutual dependence on zinc for complex stability. Chromatographic SAXS, biochemical binding assays, zinc binding measurements Scientific reports Medium 27282955
2014 DJ-1 acts as a copper chaperone for SOD1: DJ-1 binds copper ions through a novel Cys-106 site, and transfers copper to SOD1 to increase its dismutase activity, as demonstrated by fluorescence spectroscopy and biochemical SOD1 activity assays. X-ray crystallography (novel copper binding site), fluorescence spectroscopy for copper transfer kinetics, SOD1 activity biochemical assay The Journal of biological chemistry Medium 24567322
2010 ALS mutant SOD1 preferentially associates with the cytoplasmic face of spinal cord mitochondria and causes a selective decrease (>50%) in protein import into spinal cord (but not liver) mitochondria; this effect is specific to misfolded mutant SOD1 (G93A or G85R) and not wild-type SOD1 or misfolded alpha-synuclein. Mitochondrial fractionation, 2D-gel proteomics and LC-MS/MS, direct in vitro import assay with recombinant proteins Proceedings of the National Academy of Sciences of the United States of America High 21078990
2016 ALS mutant SOD1 (G93A) interacts with the stress granule protein G3BP1 in an RNA-independent manner, requiring the G3BP1 RRM domain and residues F380/F382; this interaction delays stress granule formation in response to stress stimuli and co-localizes with G3BP1-positive granules in motor neurons of mutant SOD1 mice. Co-immunoprecipitation, co-localization by immunofluorescence, stress granule dynamics assay, domain mapping by mutagenesis Acta neuropathologica Medium 27481264
2015 Alpha-synuclein physically interacts with SOD1 in living cells, human erythrocytes, and mouse brain tissue; alpha-synuclein accelerates SOD1 oligomerization independent of SOD1 dismutase activity; ALS and PD mutations in each protein modify the binding interaction. Protein-fragment complementation assay (BiFC), co-immunoprecipitation, oligomerization assay Molecular neurodegeneration Medium 26643113
2008 Metal-free (apo) forms of ALS mutant SOD1 (and wild-type) oligomerize via oxidation of free cysteines C6 and C111, forming amyloid-like soluble oligomers stabilized by inter-strand hydrogen bonds; all eleven mutants tested share this common mechanism of oligomerization when demetallated. Circular dichroism, thioflavin T binding fluorescence, size-exclusion chromatography, light scattering spectroscopy PloS one Medium 18301754
2018 Nonnative trimeric (not large fibrillar aggregate) SOD1 is the cytotoxic species in ALS: engineered trimer-stabilizing mutations (G147P) promoted motor neuron-like cell death more potently than ALS mutants A4V or G93A, while fibril-stabilizing mutations (N53I, D101I) did not impair cell viability and large aggregates competed with toxic trimer formation. Structure-guided protein engineering, gel filtration chromatography, electron microscopy, cell viability assay Proceedings of the National Academy of Sciences of the United States of America Medium 29666246
2007 Wild-type SOD1 localizes to both cytoplasm and nuclei of motoneurons, whereas mutant G93A-SOD1 is mainly cytoplasmic; this nuclear exclusion of mutant SOD1 results in higher DNA damage after oxidative stress, indicating that nuclear SOD1 provides protection from oxidative DNA damage. Immunofluorescence/confocal microscopy in transgenic mice and NSC34 cells, proteasome activity assay in subcellular fractions, comet assay for DNA damage Human molecular genetics Medium 17504823
2023 SOD1 functions as an H2S oxidase: SOD1 rapidly converts H2S to sulfate under limiting sulfide conditions; when sulfide is in molar excess, SOD1 catalyzes formation of per- and polysulfides. Loss of SOD1 increases cellular sensitivity to H2S toxicity, while SOD1 overexpression enhances tolerance, establishing an essential H2S detoxification role. Genetic knockout (yeast and human cells), overexpression experiments, biochemical H2S oxidation assay, ROS measurement Proceedings of the National Academy of Sciences of the United States of America High 36630448
2020 SOD1 regulates canonical Wnt signaling: SOD1-derived H2O2 stabilizes CK1γ (the human homolog of yeast Yck1/2), and SOD1 knockdown reduces CK1γ expression and impairs Wnt-dependent cell proliferation in human HEK293 cells. SOD1 knockdown in HEK293 cells, CK1γ expression measurement, Wnt reporter assay, cell proliferation assay Biochemical and biophysical research communications Medium 33218686
2012 SOD1 knockout in mice leads to pyruvate intolerance, decreased liver glycogen storage, reduced phosphoenolpyruvate carboxykinase and protein phosphatase activities, elevated glucokinase activity, and increased hepatic lipid profiles (cholesterol, triglycerides, free fatty acids), demonstrating SOD1's role in regulating hepatic gluconeogenesis, glycolysis, and lipogenesis. Sod1 knockout mouse model, pyruvate tolerance test, enzymatic activity assays, protein level measurements by Western blot Free radical biology & medicine Medium 22974764
2014 SOD1 binds PCBP1 (a nuclear poly(rC) binding protein) in pig brain but not mouse brain; in transgenic pigs expressing mutant G93A hSOD1, mutant SOD1 showed nuclear accumulation and formed ubiquitinated nuclear aggregates rather than cytoplasmic inclusions, suggesting the SOD1-PCBP1 interaction accounts for species-specific nuclear SOD1 accumulation. Co-immunoprecipitation from pig and mouse brain tissue, immunofluorescence, ubiquitin immunostaining in transgenic pigs Cell research Low 24577199
2024 Plekhg5 (a guanine exchange factor) drives unconventional secretion of Sod1 by sequestering it into autophagosomal carriers that fuse with secretory lysosomal-related organelles (LROs); exocytosis of LROs to release Sod1 requires activation of the small GTPase Rab26 by Plekhg5; deletion of Plekhg5 in mice causes Sod1 accumulation in LROs at presynaptic sites and reduces secretion of ALS-linked SOD1G93A. Plekhg5 knockout mice, live imaging of autophagosomal carriers, co-localization studies, iPSC-derived motoneurons, secretion assays Nature communications Medium 39366938
2021 Restoration of SOD1 expression specifically in neurons of Sod1-deficient mice (SynTgSod1-/- mice) prevents muscle mitochondrial dysfunction (elevated ROS, impaired NADH recovery), abnormal calcium handling, and NMJ denervation/fragmentation, despite continued absence of SOD1 in muscle, demonstrating that muscle mitochondrial defects in Sod1-/- mice are secondary to neuronal oxidative stress affecting NMJ innervation. Transgenic neuronal-specific SOD1 rescue, mitochondrial ROS measurement, oxygen consumption assay, intracellular calcium transient measurement, NMJ morphology analysis Free radical biology & medicine High 33561489
2011 In a zebrafish genetic epistasis analysis, SOD1 acts in a pathogenic pathway independent of FUS and TARDBP: wild-type SOD1 failed to rescue phenotypes caused by mutant FUS or TARDBP, and wild-type FUS/TARDBP failed to rescue mutant SOD1 phenotypes; overexpression of mutant SOD1 exacerbated the motor phenotype of mutant FUS. Zebrafish knockdown/overexpression genetics, motor phenotype scoring, epistasis analysis PLoS genetics Medium 21829392
2011 Mutant SOD1 A4V forms ion channel-like tetrameric pore structures (outer diameter 12.2 nm, inner diameter 3.0 nm) when reconstituted in lipid membranes, produces distinct ionic conductances not seen with wild-type SOD1, and causes membrane depolarization and intracellular calcium increase in neuroblastoma cells. Atomic force microscopy (AFM), electrophysiology (bilayer recordings), calcium imaging in neuroblastoma cells Neurobiology of disease Medium 21930207
2022 Homozygous in-frame deletion of Val119/120 in SOD1 results in complete absence of SOD1 enzymatic activity and undetectable SOD1 protein despite preserved mRNA/splicing, causing an infantile progressive motor-neurological syndrome through loss-of-function; heterozygous carriers have ~50% activity. Exome sequencing, cDNA analysis, SOD1 activity assay in erythrocyte lysates, protein quantification by Western blot Brain : a journal of neurology Medium 34788402
2019 CuO nanoparticle-induced copper overload causes SOD1 misfolding and mitochondrial translocation in macrophages; chelation of copper with tetrathiomolybdate prevented cell death while inhibition of SOD1's chaperone (CCS) aggravated toxicity, indicating copper loading disrupts normal SOD1 folding and mitochondrial localization. TEM, ICP-MS, circular dichroism spectroscopy, confocal microscopy with aggresome dye, proteasome activity assay, pharmacological inhibition Particle and fibre toxicology Low 35538581
2017 In muscle-specific SOD1G93A transgenic mice (MLC/SOD1G93A), mutant SOD1 expression triggers NMJ dismantlement via PKCθ activation: perturbation of redox signaling by muscle-accumulated SOD1G93A causally leads to morphological alterations in presynaptic terminals, high acetylcholine receptor turnover, and NMJ disintegration through a PKCθ-dependent mechanism. Transgenic mouse model with muscle-specific expression, immunofluorescence, AChR turnover assay, PKCθ activity measurement and pharmacological inhibition Antioxidants & redox signaling Medium 28931313
2021 High-fat/palmitic acid treatment decreases CCS (copper chaperone for SOD1) levels in neuronal cells, which promotes nuclear import of SOD1 and reduces its cytoplasmic dismutase activity, leading to elevated ROS; this mechanism was confirmed in high-fat diet mice showing reduced hippocampal SOD1 activity and CCS levels. Cell culture treatment with palmitic acid, CCS knockdown/measurement, SOD1 activity assay, subcellular fractionation, high-fat diet mouse model Life sciences Low 33607157

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free radical biology & medicine 1581 12126755
2022 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. The New England journal of medicine 683 36129998
2014 Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice. Annals of neurology 309 25381879
2015 Mutant SOD1 mediated pathogenesis of Amyotrophic Lateral Sclerosis. Gene 256 26657039
2013 Is SOD1 loss of function involved in amyotrophic lateral sclerosis? Brain : a journal of neurology 240 23687121
2013 SIRT5 desuccinylates and activates SOD1 to eliminate ROS. Biochemical and biophysical research communications 227 24140062
2020 SOD1, more than just an antioxidant. Archives of biochemistry and biophysics 188 33259795
2007 Mutation of SOD1 in ALS: a gain of a loss of function. Human molecular genetics 166 17504823
2002 Dorfin ubiquitylates mutant SOD1 and prevents mutant SOD1-mediated neurotoxicity. The Journal of biological chemistry 164 12145308
2013 SOD1 integrates signals from oxygen and glucose to repress respiration. Cell 162 23332757
2011 FUS and TARDBP but not SOD1 interact in genetic models of amyotrophic lateral sclerosis. PLoS genetics 152 21829392
2000 New consensus research on neuropathological aspects of familial amyotrophic lateral sclerosis with superoxide dismutase 1 (SOD1) gene mutations: inclusions containing SOD1 in neurons and astrocytes. Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases 145 11464950
2010 ALS-linked mutant superoxide dismutase 1 (SOD1) alters mitochondrial protein composition and decreases protein import. Proceedings of the National Academy of Sciences of the United States of America 137 21078990
2008 SOD1 and amyotrophic lateral sclerosis: mutations and oligomerization. PloS one 136 18301754
2022 SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity. Scientific reports 135 34996976
1995 Candida albicans ALS1: domains related to a Saccharomyces cerevisiae sexual agglutinin separated by a repeating motif. Molecular microbiology 128 7752895
2014 SOD1, an unexpected novel target for cancer therapy. Genes & cancer 117 24955214
2009 Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation. Human molecular genetics 117 19661182
2015 SOD1 in neurotoxicity and its controversial roles in SOD1 mutation-negative ALS. Advances in biological regulation 111 26563614
2018 SOD1 in Amyotrophic Lateral Sclerosis: "Ambivalent" Behavior Connected to the Disease. International journal of molecular sciences 110 29751510
2006 SOD1: a candidate gene for keratoconus. Investigative ophthalmology & visual science 108 16877401
2019 Mechanisms of SOD1 regulation by post-translational modifications. Redox biology 105 31344643
2018 SOD1 Phosphorylation by mTORC1 Couples Nutrient Sensing and Redox Regulation. Molecular cell 97 29727620
2012 SOD1 aggregation and ALS: role of metallation states and disulfide status. Current topics in medicinal chemistry 96 23339308
2016 Therapeutic rAAVrh10 Mediated SOD1 Silencing in Adult SOD1(G93A) Mice and Nonhuman Primates. Human gene therapy 90 26710998
2016 ALS mutant SOD1 interacts with G3BP1 and affects stress granule dynamics. Acta neuropathologica 90 27481264
2011 SOD1 Transcriptional and Posttranscriptional Regulation and Its Potential Implications in ALS. Neurology research international 88 21603028
2020 Silence superoxide dismutase 1 (SOD1): a promising therapeutic target for amyotrophic lateral sclerosis (ALS). Expert opinion on therapeutic targets 81 32125907
2017 Misfolded SOD1 is not a primary component of sporadic ALS. Acta neuropathologica 80 28247063
2014 DJ-1 is a copper chaperone acting on SOD1 activation. The Journal of biological chemistry 73 24567322
2018 Large SOD1 aggregates, unlike trimeric SOD1, do not impact cell viability in a model of amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences of the United States of America 70 29666246
2017 P2X7 Receptor Activation Modulates Autophagy in SOD1-G93A Mouse Microglia. Frontiers in cellular neuroscience 69 28871219
2022 Copper oxide nanoparticles trigger macrophage cell death with misfolding of Cu/Zn superoxide dismutase 1 (SOD1). Particle and fibre toxicology 63 35538581
2022 Sod1 integrates oxygen availability to redox regulate NADPH production and the thiol redoxome. Proceedings of the National Academy of Sciences of the United States of America 62 34969852
2020 Copper Sources for Sod1 Activation. Antioxidants (Basel, Switzerland) 61 32517371
2010 FUS, TARDBP, and SOD1 mutations in a Taiwanese cohort with familial ALS. Neurobiology of aging 61 20472325
2017 Muscle Expression of SOD1G93A Triggers the Dismantlement of Neuromuscular Junction via PKC-Theta. Antioxidants & redox signaling 60 28931313
2016 Silencing strategies for therapy of SOD1-mediated ALS. Neuroscience letters 60 27507699
2015 Metal-deficient SOD1 in amyotrophic lateral sclerosis. Journal of molecular medicine (Berlin, Germany) 58 25754173
2004 Functional analysis of the Candida albicans ALS1 gene product. Yeast (Chichester, England) 58 15116430
2016 ALS-linked misfolded SOD1 species have divergent impacts on mitochondria. Acta neuropathologica communications 56 27121871
2015 SOD1 silencing in motoneurons or glia rescues neuromuscular function in ALS mice. Annals of clinical and translational neurology 55 25750921
2012 Neuromuscular effects of G93A-SOD1 expression in zebrafish. Molecular neurodegeneration 55 22938571
2011 SOD1 and mitochondria in ALS: a dangerous liaison. Journal of bioenergetics and biomembranes 55 22081209
2011 Mutation analysis of VSX1 and SOD1 in Iranian patients with keratoconus. Molecular vision 54 22171159
2014 A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity. Human molecular genetics 52 25468678
2018 Metabolic Changes Associated With Muscle Expression of SOD1G93A. Frontiers in physiology 51 30042688
2021 R13 preserves motor performance in SOD1G93A mice by improving mitochondrial function. Theranostics 50 34158851
2024 Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS. Frontiers in molecular biosciences 45 38855322
2018 Aggregated SOD1 causes selective death of cultured human motor neurons. Scientific reports 45 30401824
2021 De novo mutations in SOD1 are a cause of ALS. Journal of neurology, neurosurgery, and psychiatry 44 34518333
2019 Molecular recognition and maturation of SOD1 by its evolutionarily destabilised cognate chaperone hCCS. PLoS biology 44 30735496
2005 Mutant SOD1 instability: implications for toxicity in amyotrophic lateral sclerosis. Neuro-degenerative diseases 44 16909016
2014 Species-dependent neuropathology in transgenic SOD1 pigs. Cell research 43 24577199
2023 SOD1 is an essential H2S detoxifying enzyme. Proceedings of the National Academy of Sciences of the United States of America 38 36630448
2013 Pruning the ALS-associated protein SOD1 for in-cell NMR. Journal of the American Chemical Society 38 23819500
2012 Knockout of SOD1 alters murine hepatic glycolysis, gluconeogenesis, and lipogenesis. Free radical biology & medicine 38 22974764
2020 Inhibition of TXNRD or SOD1 overcomes NRF2-mediated resistance to β-lapachone. Redox biology 37 32007910
2025 Amyotrophic lateral sclerosis caused by SOD1 variants: from genetic discovery to disease prevention. The Lancet. Neurology 34 39706636
2016 A faulty interaction between SOD1 and hCCS in neurodegenerative disease. Scientific reports 34 27282955
2015 α-synuclein interacts with SOD1 and promotes its oligomerization. Molecular neurodegeneration 33 26643113
2011 Efg1 Controls caspofungin-induced cell aggregation of Candida albicans through the adhesin Als1. Eukaryotic cell 33 22037180
2010 Heterogeneous distribution of Candida albicans cell-surface antigens demonstrated with an Als1-specific monoclonal antibody. Microbiology (Reading, England) 32 20705663
2014 Superoxide Dismutase Gene (SOD1, SOD2, and SOD3) Polymorphisms and Antituberculosis Drug-induced Hepatitis. Allergy, asthma & immunology research 31 25553268
2017 Prion Properties of SOD1 in Amyotrophic Lateral Sclerosis and Potential Therapy. Cold Spring Harbor perspectives in biology 30 28096265
2017 Implications of fALS Mutations on Sod1 Function and Oligomerization in Cell Models. Molecular neurobiology 30 28884318
2004 DSCR1(Adapt78) modulates expression of SOD1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 14718387
2001 Formation of advanced glycation end-product-modified superoxide dismutase-1 (SOD1) is one of the mechanisms responsible for inclusions common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutation, and transgenic mice expressing human SOD1 gene mutation. Neuropathology : official journal of the Japanese Society of Neuropathology 28 11304045
2021 SOD1 oligomers in amyotrophic lateral sclerosis. Current opinion in structural biology 27 33465527
2024 Tofersen for SOD1 ALS. Neurodegenerative disease management 26 39330700
2010 Case-control studies on ceruloplasmin and superoxide dismutase (SOD1) in neurodegenerative diseases: a short review. Journal of the neurological sciences 26 20851426
2023 Candida albicans Adhesins Als1 and Hwp1 Modulate Interactions with Streptococcus mutans. Microorganisms 25 37374893
2019 Cross talk between SOD1 and the mitochondrial UPR in cancer and neurodegeneration. Molecular and cellular neurosciences 25 31028834
2014 Molecular and phenotypic characterization of Als1 and Als2 mutations conferring tolerance to acetolactate synthase herbicides in soybean. Pest management science 25 24425499
2021 Molecular Alterations in Sporadic and SOD1-ALS Immortalized Lymphocytes: Towards a Personalized Therapy. International journal of molecular sciences 24 33809456
2019 Cytoplasmic Restriction of Mutated SOD1 Impairs the DNA Repair Process in Spinal Cord Neurons. Cells 24 31771229
2022 Infantile SOD1 deficiency syndrome caused by a homozygous SOD1 variant with absence of enzyme activity. Brain : a journal of neurology 23 34788402
2020 Molecular and pharmacological chaperones for SOD1. Biochemical Society transactions 23 32794552
2010 Structures of mouse SOD1 and human/mouse SOD1 chimeras. Archives of biochemistry and biophysics 22 20727846
2021 Transgenic expression of SOD1 specifically in neurons of Sod1 deficient mice prevents defects in muscle mitochondrial function and calcium handling. Free radical biology & medicine 20 33561489
2021 Implication of post-translationally modified SOD1 in pathological aging. GeroScience 20 33608813
2019 SOD1 deficiency alters gastrointestinal microbiota and metabolites in mice. Experimental gerontology 20 31805337
2019 Knockdown of GADD34 in neonatal mutant SOD1 mice ameliorates ALS. Neurobiology of disease 20 31837419
2018 PRLH and SOD1 gene variations associated with heat tolerance in Chinese cattle. Animal genetics 20 30079537
2017 Addition of exogenous SOD1 aggregates causes TDP-43 mislocalisation and aggregation. Cell stress & chaperones 19 28560609
2024 Neuroprotective Effect of a Multistrain Probiotic Mixture in SOD1G93A Mice by Reducing SOD1 Aggregation and Targeting the Microbiota-Gut-Brain Axis. Molecular neurobiology 18 38349516
2022 Neuronal-glial communication perturbations in murine SOD1G93A spinal cord. Communications biology 18 35228715
2019 An endogenous peptide marker differentiates SOD1 stability and facilitates pharmacodynamic monitoring in SOD1 amyotrophic lateral sclerosis. JCI insight 18 31092730
2016 SOD1 dimerization monitoring using a novel split NanoLuc, NanoBit. Cell biochemistry and function 18 27687581
2024 Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy. Nature communications 17 39366938
2022 Increased surface P2X4 receptors by mutant SOD1 proteins contribute to ALS pathogenesis in SOD1-G93A mice. Cellular and molecular life sciences : CMLS 17 35852606
2011 Mutant SOD1 forms ion channel: implications for ALS pathophysiology. Neurobiology of disease 17 21930207
2021 High fat suppresses SOD1 activity by reducing copper chaperone for SOD1 associated with neurodegeneration and memory decline. Life sciences 16 33607157
2020 Lipid aldehyde hydrophobicity affects apo-SOD1 modification and aggregation. Free radical biology & medicine 16 32598986
2010 A novel ALS SOD1 C6S mutation with implications for aggregation related toxicity and genetic counseling. Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases 16 21073275
2020 Cu/Zn Superoxide Dismutase (Sod1) regulates the canonical Wnt signaling pathway. Biochemical and biophysical research communications 15 33218686
2018 Semi-dominant mutation in the cysteine-rich receptor-like kinase gene, ALS1, conducts constitutive defence response in rice. Plant biology (Stuttgart, Germany) 15 30101415
2016 SOD1 gene polymorphisms in sudden sensorineural hearing loss. Acta oto-laryngologica 15 26882452
2015 Cognitive impairment in amyotrophic lateral sclerosis, clues from the SOD1 mouse. Neuroscience and biobehavioral reviews 15 26602023
2008 An analysis of the entire SOD1 gene in sporadic ALS. Neuromuscular disorders : NMD 15 18504130

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