ArticleProceedings of the National Academy of Sciences of the United States of America2012
An over-oxidized form of superoxide dismutase found in sporadic amyotrophic lateral sclerosis with bulbar onset shares a toxic mechanism with mutant SOD1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
116 citing papers in PubMed, 3 syntheses or guidelines pooled it, 193 citations in OpenAlex.
- Antibody-Based Therapeutic Interventions for Amyotrophic Lateral Sclerosis: A Systematic Literature Review.Frontiers in neuroscience · 2021Pooled it
- Aberrant Levels of Cystatin C in Amyotrophic Lateral Sclerosis: a Systematic Review and Meta Analysis.International journal of biological sciences · 2018Pooled it
- Meta-analysis of the relationship between amyotrophic lateral sclerosis and susceptibility to serum ferritin level elevation.Neurosciences (Riyadh, Saudi Arabia) · 2016Pooled it
- The effect of aging on post-translational modifications of wild-type human SOD1 and the A5V ALS mutant.GeroScience · 2026Article
- Transcriptomic and proteomic evidence for noncanonical hydrogen sulfide metabolism and immune dysregulation in Down Syndrome.Scientific reports · 2026Article
- Development of a targeted BioPROTAC degrader selective for misfolded SOD1.Nature communications · 2025Article
- Oxidative denaturation of Cu/Zn-superoxide dismutase associated with neurodegenerative diseases.Protein science : a publication of the Protein Society · 2025Article
- Use of Proteomics to Explore Biomarkers of Amyotrophic Lateral Sclerosis (ALS): Proof of Principle from Humanized SOD1 Mouse to Human ALS.ACS pharmacology & translational science · 2025Review
- Therapeutic Applications and Mechanisms of Superoxide Dismutase (SOD) in Different Pathogenesis.Biomolecules · 2025Review
- A structure-guided antibody detects SOD1 oligomers in diverse ALS genotypes.bioRxiv : the preprint server for biology · 2025Article
- Parkinson-like wild-type superoxide dismutase 1 pathology induces nigral dopamine neuron degeneration in a novel murine model.Acta neuropathologica · 2025Article
- Inhibition of Salt-Inducible Kinase 2 Protects Motor Neurons From Degeneration in ALS by Activating Autophagic Flux and Enhancing mTORC1 Activity.CNS neuroscience & therapeutics · 2025Article
- The prion-like effect and prion-like protein targeting strategy in amyotrophic lateral sclerosis.Heliyon · 2024Review
- Aberrant protein aggregation in amyotrophic lateral sclerosis.Journal of neurology · 2024Review
- Targeting low levels of MIF expression as a potential therapeutic strategy for ALS.Cell reports. Medicine · 2024Article
- Oxidized SOD1 accelerates cellular senescence in neural stem cells.Stem cell research & therapy · 2024Article
- Serum Cystatin C is a potential biomarker for predicting amyotrophic lateral sclerosis survival.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Small molecules targeting different cellular pathologies for the treatment of amyotrophic lateral sclerosis.Medicinal research reviews · 2023Review
- Selective removal of misfolded SOD1 delays disease onset in a mouse model of amyotrophic lateral sclerosis.Cellular and molecular life sciences : CMLS · 2023Article
- Insights on the Multifaceted Roles of Wild-Type and Mutated Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis Pathogenesis.Antioxidants (Basel, Switzerland) · 2023Review
56 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
Recent studies suggest that Cu/Zn superoxide dismutase (SOD1) could be pathogenic in both familial and sporadic amyotrophic lateral sclerosis (ALS) through either inheritable or nonheritable modifications. The presence of a misfolded WT SOD1 in patients with sporadic ALS, along with the recently reported evidence that reducing SOD1 levels in astrocytes derived from sporadic patients inhibits astrocyte-mediated toxicity on motor neurons, suggest that WT SOD1 may acquire toxic properties similar to familial ALS-linked mutant SOD1, perhaps through posttranslational modifications. Using patients' lymphoblasts, we show here that indeed WT SOD1 is modified posttranslationally in sporadic ALS and is iper-oxidized (i.e., above baseline oxidation levels) in a subset of patients with bulbar onset. Derivatization analysis of oxidized carbonyl compounds performed on immunoprecipitated SOD1 identified an iper-oxidized SOD1 that recapitulates mutant SOD1-like properties and damages mitochondria by forming a toxic complex with mitochondrial Bcl-2. This study conclusively demonstrates the existence of an iper-oxidized SOD1 with toxic properties in patient-derived cells and identifies a common SOD1-dependent toxicity between mutant SOD1-linked familial ALS and a subset of sporadic ALS, providing an opportunity to develop biomarkers to subclassify ALS and devise SOD1-based therapies that go beyond the small group of patients with mutant SOD1.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.