Modulation of Oxidative Stress and Inflammation via the NRF2 Signaling Pathway

Reactive oxygen species (ROS) play a crucial role in several physiological conditions, however, an excess of ROS can lead to different pathological consequences, including inflammation. On the other hand, inflammation influences various pathological consequences such as cancer, Alzheimer’s disease, atherosclerosis, and many others. Inflammation and oxidative stress are intricately intertwined, considering ROS can trigger NF-κB in response to inflammatory signals. ROS generation by polymorphonuclear neutrophils at the inflammation site leads to endothelial dysfunction and tissue injury. In this regard, the overexpression of antioxidants reduces ROS-induced NF-κB, which influences the NOX family of proteins. Apart from this, ROS generation also affects macrophage phagocytic activity. Here, the common molecular target responsible for this crosslink is the transcription factor, Nrf2 (NF-E2-related factor 2). Nrf2 is responsible for the expression of nearly 250 genes encoding for a series of enzymes engaged in glutathione and thioredoxin-mediated pathways, inflammatory pathways, autophagy, and many others.

Overall, oxidative stress is a central regulator of NF-κB activation and inflammation signaling. There are a lot of questions which need to be answered: How can we block inflammation to control oxidative stress or vice versa? Do we need to design therapeutics with simultaneous antioxidant and anti-inflammatory properties to block this pathway, and will these therapeutics succeed in combating diseases? Another essential aspect being discussed is the rapid validation of lead drug candidates to accelerate the clinical translation of potential therapeutics. This Research Topic will gather the current state of the art for engineering promising therapeutic strategies for pharmacological regulation of oxidative stress and inflammation. We invite investigators to bring Original Research, Review, Mini Review and Perspective articles that contribute new findings on the therapeutic opportunities targeting the molecular mechanisms involved in redox balance and inflammation. Potential topics include but are not limited to:

- the role of redox imbalance in inflammation
- the role of Nrf2 in disease model systems
- omics technologies
- Nrf2 activators as therapeutic agents
- Novel insights from preclinical to clinical studies on therapeutics

Keywords: Reactive oxygen species (ROS), Inflammation, Antioxidants, Nrf2, Therapeutics, Oxidative stress

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.