ArticleRedox biology2014
SOD1 oxidation and formation of soluble aggregates in yeast: relevance to sporadic ALS development.
Article in Redox biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Pooled it
- A Systematic and Comprehensive Review on Disease-Causing Genes in Amyotrophic Lateral Sclerosis.Journal of molecular neuroscience : MN · 2020Pooled it
- Protein-Driven Copper Redox Regulation: Uncovering the Role of Disulphide Bonds and Allosteric Modulation.Angewandte Chemie (International ed. in English) · 2026Article
- Copper supplementation mitigates Parkinson-like wild-type SOD1 pathology and nigrostriatal degeneration in a novel mouse model.Acta neuropathologica communications · 2025Article
- Parkinson-like wild-type superoxide dismutase 1 pathology induces nigral dopamine neuron degeneration in a novel murine model.Acta neuropathologica · 2025Article
- The Role of Amphibian AMPs Against Oxidative Stress and Related Diseases.Antibiotics (Basel, Switzerland) · 2025Review
- Neurological Diseases can be Regulated by Phase Separation.Reviews of physiology, biochemistry and pharmacology · 2025Review
- Review
- Meiotic resetting of the cellular Sod1 pool is driven by protein aggregation, degradation, and transient LUTI-mediated repression.The Journal of cell biology · 2023Article
- Structural analysis of the overoxidized Cu/Zn-superoxide dismutase in ROS-induced ALS filament formation.Communications biology · 2022Article
- Hydrogen Peroxide and Amyotrophic Lateral Sclerosis: From Biochemistry to Pathophysiology.Antioxidants (Basel, Switzerland) · 2021Review
- The peptide secreted at the water to land transition in a model amphibian has antioxidant effects.Proceedings. Biological sciences · 2021Article
- Superoxide Dismutase 1 in Health and Disease: How a Frontline Antioxidant Becomes Neurotoxic.Angewandte Chemie (International ed. in English) · 2021Review
- Implication of post-translationally modified SOD1 in pathological aging.GeroScience · 2021Review
- Post-Translational Modification Analysis of VDAC1 in ALS-SOD1 Model Cells Reveals Specific Asparagine and Glutamine Deamidation.Antioxidants (Basel, Switzerland) · 2020Article
- Merging the Multi-Target Effects of Phytochemicals in Neurodegeneration: From Oxidative Stress to Protein Aggregation and Inflammation.Antioxidants (Basel, Switzerland) · 2020Review
- Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies.International journal of molecular sciences · 2020Review
- Characterization of the activity, aggregation, and toxicity of heterodimers of WT and ALS-associated mutant Sod1.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Copper ion / HRedox biology · 2019Article
- Mechanisms of SOD1 regulation by post-translational modifications.Redox biology · 2019Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Misfolding and aggregation of copper-zinc superoxide dismutase (Sod1) are observed in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Mutations in Sod1 lead to familial ALS (FALS), which is a late-onset disease. Since oxidative damage to proteins increases with age, it had been proposed that oxidation of Sod1 mutants may trigger their misfolding and aggregation in FALS. However, over 90% of ALS cases are sporadic (SALS) with no obvious genetic component. We hypothesized that oxidation could also trigger the misfolding and aggregation of wild-type Sod1 and sought to confirm this in a cellular environment. Using quiescent, stationary-phase yeast cells as a model for non-dividing motor neurons, we probed for post-translational modification (PTM) and aggregation of wild-type Sod1 extracted from these cells. By size-exclusion chromatography (SEC), we isolated two populations of Sod1 from yeast: a low-molecular weight (LMW) fraction that is catalytically active and a catalytically inactive, high-molecular weight (HMW) fraction. High-resolution mass spectrometric analysis revealed that LMW Sod1 displays no PTMs but HMW Sod1 is oxidized at Cys146 and His71, two critical residues for the stability and folding of the enzyme. HMW Sod1 is also oxidized at His120, a copper ligand, which will promote loss of this catalytic metal cofactor essential for SOD activity. Monitoring the fluorescence of a Sod1-green-fluorescent-protein fusion (Sod1-GFP) extracted from yeast chromosomally expressing this fusion, we find that HMW Sod1-GFP levels increase up to 40-fold in old cells. Thus, we speculate that increased misfolding and inclusion into soluble aggregates is a consequence of elevated oxidative modifications of wild-type Sod1 as cells age. Our observations argue that oxidative damage to wild-type Sod1 initiates the protein misfolding mechanisms that give rise to SALS.
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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.