Wild‐type superoxide dismutase acquires binding and toxic properties of ALS‐linked mutant forms through oxidation
Why this work is in the frame
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Bibliographic record
Abstract
Recent studies suggest that superoxide dismutase (SOD1) may represent a major target of oxidative damage in neurodegenerative diseases. To test the possibility that oxidized species of wild-type (WT) SOD1 might be involved in pathogenic processes, we analyzed the properties of the WT human SOD1 protein after its oxidation in vivo or in vitro by hydrogen peroxide (H2O2) treatment. Using transfected Neuro2a cells expressing WT or amyotrophic lateral sclerosis-linked SOD1 species, we show that exposure to H2O2 modifies the properties of WT SOD1. Western blot analysis of immunoprecipitates from cell lysates revealed that, like mutant SOD1, oxidized WT SOD1 can be conjugated with poly-ubiquitin and can interact with Hsp70. Chromogranin B, a neurosecretory protein that interacts with mutant SOD1 but not with WT SOD1, was co-immunoprecipitated with oxidized WT SOD1 from lysates of Neuro2a cells treated with H2O2. Treatment of microglial cells (line BV2) with either oxidized WT SOD1 or mutant SOD1 recombinant proteins induced tumor necrosis factor-alpha and inducible nitric oxide synthase. Furthermore, exposure of cultured motor neurons to oxidized WT SOD1 caused dose-dependent cell death like mutant SOD1 proteins. These results suggest that WT SOD1 may acquire binding and toxic properties of mutant forms of SOD1 through oxidative damage.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it