An Overview of Nrf2 Signaling Pathway and Its Role in Inflammation

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 22; p. 5474
• Main Authors: Saha, Sarmistha, Buttari, Brigitta, Panieri, Emiliano, Profumo, Elisabetta, Saso, Luciano
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23-11-2020; MDPI
• Subjects: Adaptive immunity; Alzheimer's disease; Amino acids; Animals; Antigens; Antioxidants; Biomarkers; Chemical agents; Cytokines; Deoxyribonucleic acid; Disease Susceptibility; DNA; Drug development; Gene expression; Gene Expression Regulation; Heme; Heme oxygenase (decyclizing); Homeostasis; Humans; Hypersensitivity; Immune response; Immunosuppressive agents; Inflammation; Inflammation - etiology; Inflammation - metabolism; Inflammation - pathology; Kelch-Like ECH-Associated Protein 1 - chemistry; Kelch-Like ECH-Associated Protein 1 - genetics; Kelch-Like ECH-Associated Protein 1 - metabolism; Kinases; Macrophages; Metabolism; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; NF-κB protein; Oxidation-Reduction; Oxidative Stress; Oxygenase; Pathogens; Physiology; Protein Binding; Proteins; Review; Signal Transduction; Structure-Activity Relationship; Transcription factors; Tumor necrosis factor-TNF; Ubiquitin-protein ligase; Keap1; polyphenols; Nrf2; inflammation; oxidative stress
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25225474

Inflammation is a key driver in many pathological conditions such as allergy, cancer, Alzheimer's disease, and many others, and the current state of available drugs prompted researchers to explore new therapeutic targets. In this context, accumulating evidence indicates that the transcription factor Nrf2 plays a pivotal role controlling the expression of antioxidant genes that ultimately exert anti-inflammatory functions. Nrf2 and its principal negative regulator, the E3 ligase adaptor Kelch-like ECH- associated protein 1 (Keap1), play a central role in the maintenance of intracellular redox homeostasis and regulation of inflammation. Interestingly, Nrf2 is proved to contribute to the regulation of the heme oxygenase-1 (HO-1) axis, which is a potent anti-inflammatory target. Recent studies showed a connection between the Nrf2/antioxidant response element (ARE) system and the expression of inflammatory mediators, NF-κB pathway and macrophage metabolism. This suggests a new strategy for designing chemical agents as modulators of Nrf2 dependent pathways to target the immune response. Therefore, the present review will examine the relationship between Nrf2 signaling and the inflammation as well as possible approaches for the therapeutic modulation of this pathway.