Biliverdin reductase A is a major determinant of protective NRF2 signaling Article Swipe
Chirag Vasavda
,
Ruchita Kothari
,
Navneet Ammal Kaidery
,
Suwarna Chakraborty
,
Sunil Jamuna Tripathi
,
Ryan S. Dhindsa
,
Cristina Ricco
,
Shruthi Shanmukha
,
Samaneh Saberi
,
Julia E. Lefler
,
Priyanka Kothari
,
Kalyani Chaubey
,
Adele M. Snowman
,
Michael C. Ostrowski
,
Eugenio Barone
,
Lakshminarayan M. Iyer
,
L. Aravind
,
Sudarshana M. Sharma
,
Andrew A. Pieper
,
Bobby Thomas
,
Solomon H. Snyder
,
Bindu D. Paul
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2513120122
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2513120122
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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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1073/pnas.2513120122
- https://www.pnas.org/doi/pdf/10.1073/pnas.2513120122
- OA Status
- hybrid
- Cited By
- 1
- References
- 64
- OpenAlex ID
- https://openalex.org/W4414645497
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- OpenAlex ID
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https://openalex.org/W4414645497Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1073/pnas.2513120122Digital Object Identifier
- Title
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Biliverdin reductase A is a major determinant of protective NRF2 signalingWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2025Year of publication
- Publication date
-
2025-09-30Full publication date if available
- Authors
-
Chirag Vasavda, Ruchita Kothari, Navneet Ammal Kaidery, Suwarna Chakraborty, Sunil Jamuna Tripathi, Ryan S. Dhindsa, Cristina Ricco, Shruthi Shanmukha, Samaneh Saberi, Julia E. Lefler, Priyanka Kothari, Kalyani Chaubey, Adele M. Snowman, Michael C. Ostrowski, Eugenio Barone, Lakshminarayan M. Iyer, L. Aravind, Sudarshana M. Sharma, Andrew A. Pieper, Bobby Thomas, Solomon H. Snyder, Bindu D. PaulList of authors in order
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https://doi.org/10.1073/pnas.2513120122Publisher landing page
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https://www.pnas.org/doi/pdf/10.1073/pnas.2513120122Direct link to full text PDF
- Open access
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
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https://www.pnas.org/doi/pdf/10.1073/pnas.2513120122Direct OA link when available
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
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64Number of works referenced by this work
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