A potential role for NADPH oxidase (NOX1/2) in mutant huntingtin-induced anomalous neurite outgrowth
Bibliographic record
Abstract
Neurite growth is regulated by NADPH Oxidase (NOX1 and 2) and in this study, we investigate whether neuritic abnormalities observed in stem cell models of Huntington's disease relates to altered NOX function during NGF-driven differentiation of PC12 neuronal cells. NOX1 and 2 were contained in separate vesicular compartments, and by overexpression inhibited or promoted neurite extension, respectively. Expression of mutant Htt (mHtt; exon 1 fragment) accelerated neuronal induction causing longer neurites in the first phase of differentiation, but fewer and shorter mature neurites. Htt/mHtt increased NOX2 protein levels but did not change global oxidant production; However, Htt/mHtt prominently redistributed NOX activity to neurites. Oxidant production was concentrated in intraluminal vesicles in multivesicular bodies, and mHtt specifically increased secretion of NOX1 in exosomes, which demonstrated oxidant production capacity, while rerouting NOX2 to lysosomal degradation. Knockdown of TSG101, required for intraluminal vesicle formation, increased cellular levels of NOX2/p22phox and neurite growth. Our study provides new insights on the disposition of NOX enzymes in nerve cells, indicating that deficient neurites in HD may be a correlate of altered trafficking, distribution, and activity of NOX.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".