2. Academic Validation
  3. Targeting RAGE Signaling in Inflammatory Disease

Targeting RAGE Signaling in Inflammatory Disease

  • Annu Rev Med. 2018 Jan 29;69:349-364. doi: 10.1146/annurev-med-041316-085215.
Barry I Hudson 1 2,  Marc E Lippman 2 3
Affiliations

Affiliations

  • 1 Department of Cell Biology, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida 33136, USA; email: [email protected].
  • 2 University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida 33136, USA.
  • 3 Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida 33136, USA; email: [email protected].
PMID: 29106804 DOI: 10.1146/annurev-med-041316-085215
Abstract

The receptor for advanced glycation end-products (RAGE) is a multiligand pattern recognition receptor implicated in diverse chronic inflammatory states. RAGE binds and mediates the cellular response to a range of damage-associated molecular pattern molecules (DAMPs) including AGEs, HMGB1, S100s, and DNA. RAGE can also act as an innate immune sensor of microbial pathogen-associated molecular pattern molecules (PAMPs) including Bacterial endotoxin, respiratory viruses, and microbial DNA. RAGE is expressed at low levels under normal physiology, but it is highly upregulated under chronic inflammation because of the accumulation of various RAGE ligands. Blocking RAGE signaling in cell and animal models has revealed that targeting RAGE impairs inflammation and progression of diabetic vascular complications, Cardiovascular Disease (CVD), and Cancer progression and metastasis. The clinical relevance of RAGE in inflammatory disease is being demonstrated in emerging clinical trials of novel small-molecule RAGE inhibitors.

Keywords

HMGB1; S100 proteins; cancer; cardiovascular disease; diabetes; inflammation; pattern recognition receptors; receptor for advanced glycation end-products; small-molecule inhibitors.

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