Nrf2 signaling pathway: Pivotal roles in inflammation

Syed Minhaj Uddin Ahmed; Lin Luo; Akhileshwar Namani; Xiu Jun Wang; Xiuwen Tang

doi:10.1016/j.bbadis.2016.11.005

Nrf2 signaling pathway: Pivotal roles in inflammation

Biochim Biophys Acta Mol Basis Dis. 2017 Feb;1863(2):585-597. doi: 10.1016/j.bbadis.2016.11.005. Epub 2016 Nov 4.

Authors

Syed Minhaj Uddin Ahmed¹, Lin Luo², Akhileshwar Namani¹, Xiu Jun Wang³, Xiuwen Tang⁴

Affiliations

¹ Department of Biochemistry, School of Medicine, Zhejiang University, Hangzhou 310058, PR China.
² Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, PR China; School of Pharmacy, Nantong University, Nantong 226001, PR China.
³ Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, PR China.
⁴ Department of Biochemistry, School of Medicine, Zhejiang University, Hangzhou 310058, PR China. Electronic address: xiuwentang@zju.edu.cn.

PMID: 27825853
DOI: 10.1016/j.bbadis.2016.11.005

Abstract

Inflammation is the most common feature of many chronic diseases and complications, while playing critical roles in carcinogenesis. Several studies have demonstrated that Nrf2 contributes to the anti-inflammatory process by orchestrating the recruitment of inflammatory cells and regulating gene expression through the antioxidant response element (ARE). The Keap1 (Kelch-like ECH-associated protein)/Nrf2 (NF-E2 p45-related factor 2)/ARE signaling pathway mainly regulates anti-inflammatory gene expression and inhibits the progression of inflammation. Therefore, the identification of new Nrf2-dependent anti-inflammatory phytochemicals has become a key point in drug discovery. In this review, we discuss the members of the Keap1/Nrf2/ARE signal pathway and its downstream genes, the effects of this pathway on animal models of inflammatory diseases, and crosstalk with the NF-κB pathway. In addition we also discuss about the regulation of NLRP3 inflammasome by Nrf2. Besides this, we summarize the current scenario of the development of anti-inflammatory phytochemicals and others that mediate the Nrf2/ARE signaling pathway.

Keywords: ARE; Inflammation; Keap1; Nrf2; Oxidative stress; Phytochemical.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Humans
Inflammation / immunology*
NF-E2-Related Factor 2 / immunology*
NF-kappa B / immunology
NLR Family, Pyrin Domain-Containing 3 Protein / immunology
Signal Transduction*

Substances

NF-E2-Related Factor 2
NF-kappa B
NLR Family, Pyrin Domain-Containing 3 Protein