Impact of NF-κB Signaling and Sirtuin-1 Protein for Targeted Inflammatory Intervention

Author:

Das Sagar1,Mukherjee Tuhin2,Mohanty Satyajit2,Nayak Nikita2,Mal Payel3,Ashique Sumel4ORCID,Pal Radheshyam5,Mohanto Sourav6,Sharma Himanshu7

Affiliation:

1. Department of Pharmacology, Karnataka College of Pharmacy, 33/2, Thanisandra Main Rd, Chokkanahalli, Bengaluru, Karnataka, 560064, India

2. Division of Pharmacology, Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India

3. School of Pharmaceutical and Population Health Informatics, DIT University, Makkawala, Dehradun 248009, Uttarakhand, India

4. Department of Pharmaceutical Sciences, Bengal College of Pharmaceutical Sciences & Research, Durgapur 713212, West Bengal, India

5. Department of Pharmaceutical Sciences, Pandaveswar School of Pharmacy, Pandaveswar, West Bengal 713346, India

6. Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka 575018, India

7. Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad (UP)-244001, India

Abstract

Abstract: This detailed review disclosed the NF-κB pro-inflammatory gen's activity regulation and explored the therapeutic significance, activation, and inhibition. This study uncovers the structural intricacies of the NF-κB proteins and highlights the key role of SIRT1 in NF-kB signaling pathway regulation. Particularly the Rel Homology Domain (RHD), elucidating interactions and the regulatory mechanisms involving inhibitory proteins like IκB and p100 within the NF-κB signaling cascade. Disruption of the pathway is important in uncontrolled inflammation and immune disorders. This study extensively describes the role connections of canonical and non-canonical signaling pathways of NF-κB with inflammatory and cellular responses. SIRT1 belongs to the class III histone deacetylase, via RelA/p65 deacetylation, it regulates the activity of NF-κB, closely linked with the NAD+/NADH cellular ratio, influencing stress responses, aging processes, gene regulation, and metabolic pathways. This detailed study reveals SIRT1 as a crucial avenue for uncovering the role of imbalanced NF-κB in diabetes, obesity, and atherosclerosis. This study provides valuable knowledge about the therapeutic targets of inflammatory disorders.

Publisher

Bentham Science Publishers Ltd.

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