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Mechanisms of NF-κB p65 and strategies for therapeutic manipulation

Authors Giridharan S, Srinivasan M

Received 6 March 2018

Accepted for publication 29 August 2018

Published 30 October 2018 Volume 2018:11 Pages 407—419


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Ning Quan

Sivagami Giridharan,1 Mythily Srinivasan2,3

1Department of Oral Medicine, Madha Dental College, Kundrathur, Chennai, TN, India; 2Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, Indiana University Purdue University at Indianapolis, Indianapolis, IN, USA; 3Provaidya LLC, Indianapolis, IN, USA

Abstract: The transcription factor NF-κB is a critical regulator of immune and inflammatory responses. In mammals, the NF-κB/Rel family comprises five members: p50, p52, p65 (Rel-A), c-Rel, and Rel-B proteins, which form homo- or heterodimers and remain as an inactive complex with the inhibitory molecules called IκB proteins in resting cells. Two distinct NF-κB signaling pathways have been described: 1) the canonical pathway primarily activated by pathogens and inflammatory mediators, and 2) the noncanonical pathway mostly activated by developmental cues. The most abundant form of NF-κB activated by pathologic stimuli via the canonical pathway is the p65:p50 heterodimer. Disproportionate increase in activated p65 and subsequent transactivation of effector molecules is integral to the pathogenesis of many chronic diseases such as the rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and even neurodegenerative pathologies. Hence, the NF-κB p65 signaling pathway has been a pivotal point for intense drug discovery and development. This review begins with an overview of p65-mediated signaling followed by discussion of strategies that directly target NF-κB p65 in the context of chronic inflammation.

Keywords: NF-κB, inflammation, therapy

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