ArticleProceedings of the National Academy of Sciences of the United States of America2025
Biliverdin reductase A is a major determinant of protective NRF2 signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed.
- Hypomorphic biliverdin reductase a mutations define bilirubin anti-malarial threshold.iScience · 2026Article
- Microbiome-derived cancer: the catabolism of bilirubin to urobilin in the liver-gut axis and its consequences.Gastroenterology report · 2026Review
- Targeting Infected Host Cell Heme Metabolism to Kill Malaria Parasites.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Network-based prediction and real-world patient data observation identify doxycycline as a repurposable drug in Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Bilirubin Hepatic and Intestinal Transport and Catabolism: Physiology, Pathophysiology, and Benefits.Antioxidants (Basel, Switzerland) · 2025Review
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Authors and funding
22 authors.
Funding
Abstract
Biliverdin reductase A (BVRA), the terminal enzyme in heme catabolism, generates the neuroprotective and lipophilic antioxidant bilirubin. Here, we identify a nonenzymatic role for BVRA in redox regulation. Through phylogenetic, genetic, biochemical, and enzymatic assays, we found that BVRA exerts critical nonenzymatic antioxidant activity. Transcriptomic analyses further revealed that BVRA physically and genetically interacts with nuclear factor erythroid-derived factor-like 2 (NRF2), a major transcriptional regulator of cellular redox signaling. ChIP-seq and RNA-seq analyses reveal that BVRA and NRF2 coordinate the expression of antioxidant genes, many of which are typically dysregulated in neurodegenerative conditions such as Alzheimer's disease. Thus, this noncanonical BVRA-NRF2 axis controls an essential pathway of redox signaling in neuroprotection. Our findings position BVRA as a dual-function integrator of antioxidant defense across both lipophilic and hydrophilic compartments, bridging these two distinct modes of redox protection in the brain.
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Registered trials
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