Natural product screening reveals nanomolar Musashi2 inhibitor reducing forgetting in Caenorhabditis elegans
Bibliographic record
Abstract
Physiological forgetting is an essential process for normal brain function, yet the molecular mechanisms underlying memory loss, including pathologically accelerated forms, are still not fully elucidated. A key mechanism to induce forgetting was identified in Caenorhabditis elegans (C. elegans) involving the RNA-binding protein Musashi (MSI), which acts as a translational regulator. Here, we report the discovery of a series of nanomolar inhibitors of MSI identified via a high-throughput natural product screening platform of a plant extract library. Ellagic acid (EA) emerged as one of the most potent inhibitors, improving both short- and long-term associative memory in an all-or-none like manner in an in vivo C. elegans memory model. Notably, EA had no effect in msi loss-of-function mutant worms, corroborating MSI as its molecular target. These findings underscore MSI as a therapeutic target for modulating forgetting and establish EA as a nanomolar MSI inhibitor and promising lead compound for mitigating memory decay.
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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".