Chymotrypsin‐like proteases contribute to human monocytic THP‐1 cell as well as human microglial neurotoxicity
Bibliographic record
Abstract
Activated microglia have been observed in various neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, and multiple sclerosis. They may exacerbate neuronal damage by secreting various toxic molecules. The list of candidate toxins includes proteases. Since it is currently not known which, if any, proteases are involved in human microglia neurotoxicity, we studied the effects of a panel of protease inhibitors on the toxicity of cell-free supernatants of stimulated human microglia and THP-1 monocytic cells to human SH-SY5Y cells. Five structurally distinct inhibitors that are known to inhibit chymotrypsin-like proteases were partially protective. They included chymostatin, AEBSF (Pefabloc SC), alpha1-antichymotrypsin, bromoenol lactone, and 3,4-dichloroisocoumarin. The data suggest that certain protease inhibitors could inhibit microglial-mediated toxicity. They might represent a novel class of drugs with benefit in diseases where overactivity of microglia contributes to the pathogenesis.
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".