Molecular Characteristics of RAGE and Advances in Small-Molecule Inhibitors

Int J Mol Sci. 2021 Jun 27;22(13):6904. doi: 10.3390/ijms22136904.

Abstract

Receptor for advanced glycation end-products (RAGE) is a member of the immunoglobulin superfamily. RAGE binds and mediates cellular responses to a range of DAMPs (damage-associated molecular pattern molecules), such as AGEs, HMGB1, and S100/calgranulins, and as an innate immune sensor, can recognize microbial PAMPs (pathogen-associated molecular pattern molecules), including bacterial LPS, bacterial DNA, and viral and parasitic proteins. RAGE and its ligands stimulate the activations of diverse pathways, such as p38MAPK, ERK1/2, Cdc42/Rac, and JNK, and trigger cascades of diverse signaling events that are involved in a wide spectrum of diseases, including diabetes mellitus, inflammatory, vascular and neurodegenerative diseases, atherothrombosis, and cancer. Thus, the targeted inhibition of RAGE or its ligands is considered an important strategy for the treatment of cancer and chronic inflammatory diseases.

Keywords: RAGE; disease; drug; inhibitor; multi-ligands.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Susceptibility
  • Drug Discovery*
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Targeted Therapy*
  • Polymorphism, Genetic
  • Protein Isoforms
  • Receptor for Advanced Glycation End Products / antagonists & inhibitors*
  • Receptor for Advanced Glycation End Products / chemistry
  • Receptor for Advanced Glycation End Products / genetics
  • Receptor for Advanced Glycation End Products / metabolism*
  • Signal Transduction / drug effects
  • Structure-Activity Relationship

Substances

  • Glycation End Products, Advanced
  • Ligands
  • Protein Isoforms
  • Receptor for Advanced Glycation End Products