Tau protein phosphorylation at Thr<sup>175</sup> initiates fibril formation via accessibility of the N‐terminal phosphatase‐activating domain
Bibliographic record
Abstract
Abstract One of the neuropathological hallmarks of the tauopathies is the formation of neuronal cytoplasmic inclusions and fibrils of microtubule‐associated tau protein (tau). The phosphorylation of Thr175 of tau (pThr175 tau) appears to be sufficient for fibril formation in vitro and in vivo, but the mechanism by which this initiates fibril formation is unknown. Using transient transfections of tau mutants into HEK293T cells, we determined that the phosphorylation of Thr175 leads to exposure of the tau N‐terminal phosphatase‐activating domain (PAD). The exposed PAD is known to interact with protein phosphatase‐1 (PP1) resulting in glycogen synthase kinase 3β (GSK3β) activation. In vivo, a single traumatic controlled cortical injury in rats also resulted in the phosphorylation of Thr175 and increased exposure of tau PAD followed by pathological tau fibril formation. Taken together, these data suggest that neurotoxicity may be precipitated by phosphorylation at Thr175 and subsequent tau PAD exposure, GSK3β activation and tau fibril formation. image Cover Image for this issue: doi: 10.1111/jnc.14767 .
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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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.021 | 0.008 |
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".