The RAGE Axis: A Relevant Inflammatory Hub in Human Diseases

Area of Science:

• Molecular Biology
• Immunology
• Pathophysiology

Background:

• The receptor of advanced glycation end-products (RAGE) was identified in 1992 as a cell surface receptor.
• RAGE binds advanced glycation end-products (AGEs), formed from non-enzymatic glycation of proteins and lipids.
• Initially linked to diabetes, RAGE's role is now recognized in various human diseases.

Purpose of the Study:

• To review the fundamental biology of the RAGE axis.
• To summarize RAGE's contribution to the pathophysiology of major human diseases.
• To highlight RAGE as a pattern recognition receptor (PRR).

Main Methods:

• Literature review of RAGE axis biology.
• Analysis of RAGE's role in disease pathogenesis.
• Synthesis of evidence on RAGE ligands and signaling.

Main Results:

• RAGE recognizes a diverse array of ligands beyond AGEs.
• RAGE ligation triggers complex intracellular signaling cascades.
• The RAGE axis is a key player in metabolic, neurodegenerative, cardiovascular, autoimmune, and airway diseases, and cancer.

Conclusions:

• The RAGE axis is a critical mediator in numerous human diseases.
• Understanding RAGE signaling is crucial for disease intervention.
• RAGE's broad ligand-binding capacity underscores its significance in innate immunity and disease.