P2‐086: Inhibition of beta‐amyloid peptide aggregation by scyllo‐inositol rescues the autophagic deficits in the TgCRND8 mouse model of Alzheimer's disease
Bibliographic record
Abstract
Discovery of scyllo-Inositol (SI), an endogenous inositol stereoisomer, as an inhibitor of amyloid-beta peptide (Aβ) aggregation and fibril formation led to clinical trials using SI to treat Alzheimer's disease (AD) patients. Taken into consideration the potential shown in the trials thus far, we aim to gain a more detailed understanding of the mechanism of action of SI. Previous studies reported the extensive accumulation of autophagic vacuoles (AVs) and autophagy dysfunction as important pathological features of AD. We examined whether SI treatment had a beneficial effect on autophagic pathways in the TgCRND8 mouse model of AD. TgCRND8 mice were treated with SI for 4 weeks starting at 12 weeks of age. We used a combination of ultra-structural and biochemical techniques to measure changes in AV induction, AV turnover, and AV degradation by lysosomes. AV accumulation in TgCRND8 mice is accompanied by changes in autophagic proteins involved in AV-lysosome fusion and lysosomal degradation as well as increased proteolytic activity in the lysosomes. SI treatment mitigated autophagy impairment by decreasing the size and the number of accumulated AVs and the associated abnormalities in lysosomal proteins. Normal cellular trafficking was also restored in the SI-treated TgCRND8 mice. We conclude that the beneficial effects of SI-A b interactions in AD mouse model brains may include rescuing of deficiencies in the latter stages of the autophagic pathway.
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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".