Investigating the interactions of bisphosphonates with amyloid beta (Aβ) proteins
Bibliographic record
Abstract
The unmet therapeutic need for a devastating neurodegenerative disorder, Alzheimer’s disease (AD), which is marked by the deposition of beta-amyloid (Aβ) plaques in the brain - mandates the development of novel anti-Aβ therapies. We investigated the drug-repurposing potential of the bisphosphonate (BPs) class of drugs as anti-Aβ agents. It is known that women are more prone to get AD and are also observed to suffer from osteoporosis after menopause. Therefore, we determined the interactions of BPs with Aβ proteins. The anti-Aβ-aggregation activity against the Aβ40 peptide was evaluated by conducting fluorescence aggregation kinetic studies, transmission electron microscopy (TEM), and computational modeling. Preliminary results suggested that BPs exhibit anti-Aβ activity. Risedronate and alendronate were identified as promising inhibitors of Aβ aggregation. Molecular docking studies for the dimer model of Aβ40 peptide indicated that both risedronate and alendronate showed interactions in the aggregation-prone region of the dimer peptide model. These studies demonstrate that BPs exhibit anti-Aβ activity in vitro and can be used to discover and develop novel anti-AD agents.
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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 | 0.000 |
| 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".