Structure-based drug design approach to target toll-like receptor signaling pathways for disease treatment

Mohammed Alaidarous

doi:10.4314/tjpr.v16i9.35

Abstract

Toll-like receptor (TLR) signaling pathways are the first line of defence against many microbial organisms. The question of how TLRs recognize endogenous ligands remains controversial. Several studies have shown that TLRs are implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Therefore, in structure-based drug design, TLRs are now viewed as potential therapeutic targets in the treatment of autoimmune diseases. This review shows how proteins, specifically TLRs, are used as therapeutic targets to design inhibitors (drugs) using the structure-based drug design approach for disease treatment. Keywords: Structure-based drug design, Toll-like receptors, Autoimmune diseases, Endogenous ligands, X-ray crystallography, Homology modeling

Highlights

Structure-based drug design has been a thriving field since the human genome project was completed
Various families of Toll-like receptor (TLR) have been identified and due to their importance in defense against pathogens, they have been viewed as potential drug targets in the treatment of diseases such as autoimmune disorders [29]
Immunoregulators, such as IRS-954, inhibit cascade activated by TLR7 and TLR9 to treat systemic lupus erythematosus [40]

Summary

INTRODUCTION

Structure-based drug design has been a thriving field since the human genome project was completed. Various families of TLRs have been identified and due to their importance in defense against pathogens, they have been viewed as potential drug targets in the treatment of diseases such as autoimmune disorders [29]. These are substances that work in synergy with TLRs to enhance their functioning. ISS1018 triggers the release of immunoglobulin and interferon (IFNα) by Bcells and causes dendritic cells to release TNFα, interleukin-12 and interferon-β [39] Immunoregulators, such as IRS-954, inhibit cascade activated by TLR7 and TLR9 to treat systemic lupus erythematosus [40]. It is a human monoclonal antibody that prevents the activation of soluble Bcells, resulting in the programmed cell death of autoreactive B lymphocytes [47]

CONCLUSION

Conflict of Interest