On the contribution of Tau phosphorylation to nuclear and cytoplasmic changes in human neuroblastoma cells
Bibliographic record
Abstract
Human tauopathies are characterized by intracellular aggregation of hyperphosphorylated tau protein in neurons. Tau is involved in many cellular functions through its association with microtubules and actin filaments. In tauopathies overstabilization of filamentous actin (f-actin) leads to invagination of nuclear envelope. An intricate protein layer known as Nuclear Lamina (NL) is located at the interface of inner layers of nuclear envelope and chromatin. NL is degraded after nuclear envelope invagination, resulting in aberrant gene expression and re-emergence of ancient retroviruses. It is not clear if inhibition of kinases involved in tau pathology can prevent NL invagination and its downstream events. In this study, we first established that overexpression of full-length tau (FL-Tau) and the 35kDa C-terminal fragment (Tau35) in differentiated human neuroblastoma (dSH-SY5Y) cell lines enhanced nuclear lamina invagination and overstabilization of filamentous actin; however, these changes were significantly exacerbated in Tau35-overexpressing cells. Application of two small molecule inhibitors of c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-3β (GSK-3β) reduced the extent of damages in tau-overexpressing cells. JNK inhibitor significantly decreased NL invagination in dSH-SY5Y-FL-Tau and -Tau35 cells. Furthermore, GSK-3β inhibition alleviated f-actin overstabilization in dSH-SY5Y-FL-Tau cells. In conclusion, we identified that NL invagination and f-actin overstabilization could be modulated by inhibition of involving kinases in tauopathies.
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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".