An Overview of Nrf2 Signaling Pathway and Its Role in Inflammation

Abstract

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.

Redox Homeostasis in Poultry: Regulatory Roles of NF-κB

“…Proof of the interaction and cooperative action of Nrf2 and NF-κB was taken from experimental work with various model systems employing plant extracts, individual compounds in vitro and in vivo, pure chemicals, and some known toxicants [ 6 ]. In our recent review, a central role of Nrf2 in antioxidant defenses and vitagene regulation was described in detail [ 27 ], and it seems likely that, under oxidative stress, the transcription factors NF-κB and Nrf2 antagonize each other to coordinate a stress response [ 60 , 67 , 76 ].…”

“…Redox biology is a very quickly developing area of modern biological sciences, and roles of redox homeostasis in health and disease have recently received tremendous attention [ 1 , 2 , 3 , 4 , 5 , 6 ]. There are a range of redox pairs in cells/tissues responsible for redox homeostasis maintenance/regulation.…”

“…Among them are proteins Keap1, an inhibitor of Nrf2, and IκB, an inhibitor of NF-κB, which have received a lot of recent attention. Indeed, oxidation of SH groups in Cys of Keap1 or phosphorylation of IκB are important triggers for nuclear translocation and activation of Nrf2 and NF-κB—important players in the redox homeostasis regulation [ 6 ]. In particular, a recent model suggests regulation of all collaborating metabolic organs in the body through changes in circulating redox metabolites [ 5 ].…”

Renoprotective Effects of DPP-4 Inhibitors

“…Furthermore, accumulating evidence indicates that the transcription factor Nrf2 plays a pivotal role in regulating redox homeostasis by increasing antioxidant genes to maintain intracellular redox homeostasis. Nrf2 is known to stimulate the heme oxygenase-1 (HO-1) axis, which is a potent anti-inflammatory target [ 44 ]. It has been reported that DPP-4 inhibitors activate the Nrf2/HO-1 pathway [ 45 , 46 , 47 ].…”

“…BNP is clinically used for the diagnosis and evaluation of CVD [ 69 ]. BNP is synthesized as a 134-amino acid precursor (prepro BNP) that is processed to proBNP [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , …”