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.
Highlights
Receptor for advanced glycation end-products (RAGE) was first isolated from the human lung library in 1992 and noted for its ability to act as a receptor for advanced glycation end products (AGEs)
RAGE and its ligands are present on most cell types and are involved in diabetes, diabetes complications, chronic inflammation, neurodegenerative disorders, and cancer
Recent advances have revealed the enormous breadth of the influence of RAGE and its ligands
Summary
RAGE (receptor for advanced glycation end-products) was first isolated from the human lung library in 1992 and noted for its ability to act as a receptor for advanced glycation end products (AGEs). Ligand stimulation of RAGE activates signal transduction pathways, such as the diaphanous-related formin 1 (DIAPH1), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/AKT, and Toll-interleukin. Upregulated RAGE expression has been reported in diabetes mellitus, atherosclerosis, rheumatoid arthritis, Alzheimer’s disease (AD), cardiovascular diseases (CVDs), and immune/inflammatory diseases [21,22,23,24,25], and has been shown to be related to the developments and progressions of different cancer types [26]
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