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 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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".