OPTN attenuates the neurotoxicity of abnormal Tau protein by restoring autophagy
Bibliographic record
Abstract
OPTN is an autophagy receptor involved in autophagic degradation. Here we studied the role of OPTN in attenuating the neurotoxicity induced by mutated Tau protein. We constructed recombinant adeno-associated viruses with OPTN and Tau-P301L genes, respectively. Through virus coinfection on neuronal cell line HT22 in vitro and Kunming mice in vivo, we found that autophagy- and apoptosis-associated genes are altered by Tau-P301L at both mRNA and protein levels, which are restored by OPTN expression. Functionally, OPTN suppresses apoptosis and enhances cellular viability in Tau-P301L expressing HT22 cells, and increases learning and memory in Tau-P301L expressing mice, respectively. Last, we found that OPTN reduces the p-Tau levels in vitro and in vivo. Our results reveal the function of OPTN in lowering the p-Tau level and the expressions of apoptosis genes, and increasing the expressions of autophagic genes, indicating a beneficial role of OPTN in Tau pathology.
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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) | 0.001 | 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".