Targeting NINJ1-mediated cell rupture to treat inflammatory diseases
Bibliographic record
Abstract
Cell death can terminate in plasma membrane rupture to release potent pro-inflammatory intracellular contents thereby contributing to inflammatory diseases. Cell rupture is an active process, mediated by the membrane protein ninjurin-1 (NINJ1) in pyroptosis, post-apoptosis lysis, ferroptosis, and forms of necrosis. Once activated, NINJ1 clusters into large oligomers within the membrane to initiate cellular lysis. Recent preclinical studies have demonstrated that inhibiting NINJ1 is a new strategy for treating immune-mediated diseases. Indeed, both small molecule inhibitors and neutralizing antibodies can target NINJ1 clustering to preserve plasma membrane integrity and mitigate disease pathogenesis. In this Perspective, we provide a summary of the current state of knowledge and recent developments in targeting cellular integrity during cell death through NINJ1 inhibition to treat inflammatory disease, with a focus on liver injury. As these NINJ1-mediated cell death pathways are pivotal in maintaining health and contribute to disease pathogenesis when dysregulated, the studies discussed within have broad implications across the immunologic basis of molecular medicine.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 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".