Chemical genomics and molecular medicine
Bibliographic record
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease that, in its most common form, occurs as dementia in people over 65 years old although early onset form also exists. Currently it afflicts 24 million people worldwide. The disease is characterized in the brain by abnormal clumps (amyloid plaques) and tangled bundles of fibers (neurofibrillary tangles) composed of misplaced proteins. Three neurotransmitters commonly affected by AD are acetylcholine, serotonin, and nor epinephrine. The cholinergic system-the nerve cell system in the brain that uses acetylcholine as a neurotransmitter-is the most dramatic of the neurotransmitter systems affected by Alzheimer's disease. Acetylcholinesterase is one of the most crucial enzymes that hydrolyze acetylcholine in the brain to choline and acetic acid at cholinergic synapses, leading to nerve response and function. Potentiation of central cholinergic activity has been proposed as a therapeutic approach for improving the cognitive function in patients with Alzheimer's disease (AD). Increasing the acetylcholine concentration in the brain by modulating/inhibiting acetylcholinesterase (AchE) activity is among the most promising therapeutic strategies. In our studies attempts were made to produce potential natural acetylcholinesterase inhibitors. More than eight hundred compounds were taken from different natural sources. Initial in-silico screening of molecules was based on docking score between acetylcholinesterase and compounds taken from the natural sources. The hits were further analyzed and narrowed by applying Lipinski's rule-of-five analysis. Molecules with high ability to cross blood brain barrier were taken for energy minimization and quantitative structure activity studies. The biological activity of promising compounds was predicted by using PASS prediction analysis. Ferulic acid and Caffeic acid found in garlic showed very good IC50 values and satisfied the standard drug-like properties with remarkable pharmacokinetics and pharmacodynamics abilities. Thus we hypothesize that ferulic acid and caffeic acid which is obtained from garlic can be used as an effective acetylcholinesterase inhibitors in the early stage of Alzheimer's disease. Wet lab studies were conducted on the Swiss Albino mice as the animal model to check the inhibition of acetycholinestrerase by ferulic acid and caffeic acid.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".