Redox Regulation by Nrf2 in Health and Disease

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 30 August 2026 | Viewed by 1114

Special Issue Editor


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Guest Editor
Department of ODS and Research, School of Dentistry, Meharry Medical College, Nashville, TN 37208, USA
Interests: nitric oxide; GI motility; oral and systemic connection; vascular neuropeptides; Nrf2
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Special Issue Information

Dear Colleagues,

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of cellular antioxidant responses, playing a crucial role in maintaining redox homeostasis. This Special Issue of Cells aims to gather cutting-edge research that explores the diverse roles of Nrf2-mediated redox regulation across various biological systems and conditions. We invite submissions from researchers working on different aspects of Nrf2 biology, including but not limited to:

  • Molecular Mechanisms: Studies elucidating the molecular mechanisms governing Nrf2 activation and regulation, including post-translational modifications, interactions with Keap1, and other regulatory proteins.
  • Cellular Physiology: Investigations into how Nrf2 influences mitochondrial function, autophagy, apoptosis, and other fundamental cellular processes.
  • Signaling Crosstalk: Research exploring the crosstalk between Nrf2 and other signaling pathways such as NF-κB, p53, and mTOR, and their implications for cell survival and stress response.
  • Gene Expression and Epigenetics: Analyses of Nrf2-targeted genes and epigenetic modifications that contribute to antioxidant defense and cellular adaptation to oxidative stress.
  • Inflammation and Immunity: Studies examining the role of Nrf2 in modulating inflammatory responses and immune functions.
  • Pharmacological Modulation: Discoveries of novel pharmacological agents or natural compounds that target Nrf2 pathways for therapeutic purposes, focusing on preclinical models and mechanisms rather than clinical trials.
  • Model Organisms and In Vitro Systems: Contributions using model organisms (e.g., yeast, C. elegans, Drosophila, zebrafish, mice) or in vitro systems to study Nrf2 function under physiological and pathological conditions.

By covering these broad areas, this Special Issue seeks to provide a comprehensive overview of the current state of knowledge regarding Nrf2's multifaceted roles in health and disease. We encourage submissions of original research articles, reviews, and perspectives that advance our understanding of Nrf2 biology and its potential applications in basic science and translational research.

We look forward to receiving high-quality contributions that will enrich our understanding of Nrf2’s critical functions in redox regulation and beyond.

Dr. Pandu Gangula
Guest Editor

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Keywords

  • Nrf2
  • redox
  • cellular stress response
  • antioxidant gene regulation
  • signaling pathway crosstalk
  • oxidative stress response

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Published Papers (1 paper)

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Research

25 pages, 4735 KB  
Article
Role of Nitric Oxide and Nrf2 to Counteract Vascular Endothelial Dysfunction Induced by Periodontal Pathogens Using HUVECs
by Gunaraj Dhungana, Chethan Sampath, Vineeta Sharma, Olga Korolkova and Pandu R. Gangula
Cells 2025, 14(22), 1777; https://doi.org/10.3390/cells14221777 - 12 Nov 2025
Viewed by 815
Abstract
Background: Polybacterial infections associated with periodontitis are increasingly linked to systemic vascular complications, yet the underlying endothelial mechanisms remain unclear. This study investigated how a consortium of red-complex bacteria (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola) and orange complex ( [...] Read more.
Background: Polybacterial infections associated with periodontitis are increasingly linked to systemic vascular complications, yet the underlying endothelial mechanisms remain unclear. This study investigated how a consortium of red-complex bacteria (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola) and orange complex (Fusobacterium nucleatum) affects oxidative stress, inflammation, metabolism, and apoptosis in endothelial cells, and whether L-Sepiapterin [a tetrahydrobiopterin (BH4) precursor via salvage pathway] or bardoxolone methyl (CDDO-Me) [a potent nuclear factor erythroid 2-related factor 2 (Nrf2) activator)] could provide protection. Methods: Human umbilical vein endothelial cells (HUVECs) were infected for 12–72 h and treated with L-Sepiapterin or CDDO-Me. Nitric oxide (NO), BH4, and reactive oxygen species (ROS) levels were quantified, and mRNA expression of key genes regulating nitric oxide synthase activity, antioxidant defense, inflammation (TLR4/NF-κB, cytokines), metabolism (PI3K-AKT-PEA-15), and apoptosis (FAS–caspase pathway) was analyzed. Results: Infection markedly reduced NO and BH4, elevated ROS, activated TLR4/NF-κB and proinflammatory cytokines, disrupted PI3K/AKT signaling, and triggered endothelial apoptosis. Treatments with L-Sepiapterin and CDDO-Me restored NO bioavailability, reduced oxidative and inflammatory responses, normalized metabolic gene expression, and attenuated apoptosis, with CDDO-Me showing more promising effects. This study provides the mechanistic insight linking periodontal polybacterial infection to endothelial dysfunction and metabolic impairment such as diabetes, suggesting that redox-modulating strategies such as L-Sepiapterin and CDDO-Me may help prevent vascular damage associated with periodontal disease. Full article
(This article belongs to the Special Issue Redox Regulation by Nrf2 in Health and Disease)
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