RAGE: therapeutic target and biomarker of the inflammatory response--the evidence mounts.
The RAGE binds multiple ligand families linked to hyperglycemia, aging, inflammation, neurodegeneration, and cancer. Activation of RAGE by its ligands stimulates diverse signaling cascades. The recent observation that the cytoplasmic domain of RAGE interacts with diaphanous or mDia-1 links RAGE signal transduction to cellular migration and activation of the Rho GTPases, cdc42 and rac-1. Pharmacological blockade of RAGE or genetic deletion of RAGE imparts significant protection in murine models of diabetes, inflammatory conditions, Alzheimer's disease, and tumors. Intriguingly, soluble forms of RAGE, including the splice variant-derived esRAGE, circulate in human plasma. Studies in human subjects suggest that sRAGE levels may be modulated by the diseases impacted by RAGE and its ligands. Thus, in addition to being a potential therapeutic target in chronic disease, monitoring of plasma sRAGE levels may provide a novel biomarker platform for tracking chronic inflammatory diseases, their severity, and response to therapeutic intervention.
Ramasamy
Ravichandran
R
Division of Surgical Science, Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
Yan
Shi Fang
SF
Schmidt
Ann Marie
AM
D015415:Biomarkers / Q000097:blood; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D018448:Models, Immunological; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012995:Solubility
D015415:Biomarkers; D017127:Glycation End Products, Advanced; D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic