Glucocorticoid-mediated Aβ and SCG10 upregulation evoke microtubule dysfunction and memory deficits
Bibliographic record
Abstract
Abstract We investigated glucocorticoid, a major risk factor of Alzheimer’s disease, promoted microtubule instability that culminates in memory deficits. Mice group exposed to corticosteroid had reduced trafficking of AMPAR1/2 and mitochondria into the synapse due to microtubule destabilization, which finally impaired cognitive function. Furthermore, cortisol reduced microtubule stability through the mitochondria glucocorticoid receptor (GR)-dependent pathway in SH-SY5Y cells. Cortisol translocated the Hsp70-bound GR into mitochondria before stimulating ER-mitochondria interaction via increasing GR-Bcl-2 complex. Subsequently, Aβ was produced since γ-secretase activity was upregulated by increased ER-mitochondria connectivity. Mitochondrial Ca 2+ influx was also elevated due to ER-mitochondria bridging, resulting in activation of mTOR pathway. Subsequent autophagy inhibition failed to remove Aβ and led to its accumulation. Moreover, selective autophagy through ubiquitination of SCG10 was suppressed. We eventually showed that both elevated Aβ and SCG10 levels drive cells to fail trafficking AMPAR1/2 and mitochondria into the cell terminus. In conclusion, glucocorticoid regulates ER-mitochondria coupling, which evokes Aβ generation and SCG10 upregulation. Subsequent microtubule destabilization leads to memory impairment through failure of AMPAR1/2 or mitochondria transport into cell periphery.
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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) | 0.001 | 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 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".