P3‐286: Biophysical characterization of scyllo‐inositol‐Aβ interactions
Bibliographic record
Abstract
scyllo-Inositol, ELND005, is a small molecule that is presently in phase II clinical trials for AD. Although our preclinical data demonstrated the efficacy in mouse models of AD, the direct binding of scyllo-inositol with Aβ is not well understood. Our previous in vitro data suggest that scyllo-inositol inhibits Aβ42 fibrillogenesis and stabilizes a small Aβ conformer but not Aβ40. To further understand this interaction, we examined the physical characteristics of this conformer using several biophysical approaches. Atomic force microscopy, neutral loss screening method using a triple quadrupole mass spectrometer and X-ray diffraction were utilized. By in situ atomic force microscopy we confirmed earlier electron microscopy data that Aβ42 fibres are not formed in the presence of scyllo-inositol, but rather form a mixture of conformer sizes. By collision-induced dissociation mass spectrometry, which incorporates a capillary ultra high pressure HPLC system coupled to a triple quadrupole mass spectrometer, we were able to measure the binding stoichiometry of the Aβ42-scyllo-inositol complex. We also demonstrated that scyllo-inositol preferentially binds to Aβ42 rather than Aβ40 under physiological conditions. Comparison of x-ray diffraction patterns from Aβ in the presence and absence of scyllo-inositol demonstrated an absence of the intersheet reflection for Aβ42 in the presence of scyllo-inositol whilst no changes could be detected for Aβ40. Altogether, our results suggest that scyllo-inositol binds to Aβ42 in a 2:1 ratio thereby inhibiting aggregation through interaction between the two C-terminal residues and the neighbouring ones that stabilizes the β-sheet formation of Aβ42.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".