Axonal pathology in hPSC-based models of Parkinson’s disease results from loss of Nrf2 transcriptional activity at the Map1b gene locus
Bibliographic record
Abstract
Significance Neurological dysfunction in Parkinson’s disease (PD) is highly associated with pathological deposits of aggregated α-synuclein (α-syn) in the brain, and yet an understanding of how early α-syn deposits bring about neuronal dysfunction remains elusive. This study exploits stem cell technology to model PD using two human isogenic stem cell models of the disease. Using these systems, we have identified a mechanism whereby mutant α-syn inhibits the antioxidant response, which, in turn, leads to axonal pathology through loss of expression of microtubule stabilizing proteins. We show that reactivation of this pathway can rescue axonal neuropathology. This is a demonstration of modulation of cytoskeletal elements as a potential therapy against PD, providing a previously unknown link between α-syn mutation and the antioxidant pathway.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".