NRF2 signalling in cytoprotection and metabolism
Bibliographic record
Abstract
The KEAP1-NRF2 system plays a central role in cytoprotection in defence mechanisms against oxidative stress. The KEAP1-NRF2 system has been regarded as a sulfur-utilizing cytoprotective mechanism, because KEAP1 serves as a biosensor for electrophiles by using its reactive thiols and NRF2 is a transcriptional factor regulating genes involved in sulfur-mediated redox reactions. NRF2 is a key regulator of cytoprotective genes, such as antioxidant and detoxification genes, and also possesses potent anti-inflammatory activity. Recently NRF2 has been the focus of attention as a regulator of cellular metabolism and mitochondrial function. The NRF2-mediated regulatory mechanisms of metabolites and mitochondria have been considered diverse, but have not yet been fully clarified. This review article provides an overview of molecular mechanisms that regulate NRF2 signalling and its cytoprotective roles, and highlights NRF2 contribution to cellular metabolism, particularly in the context of mitochondrial function and newly-found sulfur metabolism. LINKED ARTICLES: This article is part of a themed issue Recent Innovations in Targeting Redox Biology for Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.1/issuetoc.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".