SUMO1 Modification of Tau in Progressive Supranuclear Palsy
Bibliographic record
Abstract
Small ubiquitin-like modifiers (SUMO) have been implicated in several neurodegenerative diseases. SUMO1 conjugation has been shown to promote aggregation and regulate phosphorylation of the tau protein linked to Alzheimer's disease and related tauopathies. The current study has demonstrated that SUMO1 co-localizes with intraneuronal tau inclusions in progressive supranuclear palsy (PSP). Immunoprecipitation of isolated and solubilized tau fibrils from PSP tissues revealed SUMO1 conjugation to a cleaved and N-terminally truncated tau. The effects of SUMOylation were examined using tau-SUMO fusion proteins which showed a higher propensity for tau oligomerization of PSP-truncated tau and accumulation on microtubules as compared to the full-length protein. This was found to be specific for SUMO1 as the corresponding SUMO2 fusion protein did not display a significantly altered cytoplasmic distribution or aggregation of tau. Blocking proteasome-mediated degradation promoted the aggregation of the tau fusion proteins with the greatest effect observed for truncated tau-SUMO1. The SUMO1 modification of the truncated tau in PSP may represent a detrimental event that promotes aggregation and impedes the ability of cells to remove the resulting protein deposits. This combination of tau truncation and SUMO1 modification may be a contributing factor in PSP pathogenesis.
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How this classification was reachedexpand
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 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".