High mobility group box 1 protein/Receptor for advanced glycation end products signaling pathway (HMGB1/RAGE axis)

The High mobility group box 1 protein/Receptor for advanced glycation end products signaling pathway refers to the critical axis in which extracellular HMGB1 binds to the cell-surface receptor RAGE, triggering a variety of intracellular signaling cascades—including NF-κB, MAPK, PI3K/AKT, and JAK/STAT pathways—that lead to inflammatory cytokine production, cell migration, survival, proliferation, apoptosis, and angiogenesis. This pathway is widely implicated in the pathogenesis of cancer, inflammatory and autoimmune diseases, neurodegeneration, cardiovascular disease, and infection. Both HMGB1 and RAGE are considered therapeutic targets, and pharmacological inhibitors of their interaction are under investigation for treatment of these disorders. The complexity of functions arises from the diverse roles of HMGB1/RAGE in innate and adaptive immunity, cell stress responses, and tissue remodeling

Other names

High mobility group box 1 (HMGB1)Receptor for advanced glycation end products (RAGE)HMGB1-RAGE axisAdvanced glycation end products receptorAGEs receptorDAMPs receptor (contextual)

Inhibition of HMGB1-RAGE binding reduces downstream NF-κB, MAPK, PI3K/AKT, mTOR, and ERK1/2 signaling\nSuppression of inflammatory cytokine release\nBlocking cell migration and invasion\nInduction of apoptosis/autophagy