Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 60, Issue 17, Pages 7213-7232Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.7b00058
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Funding
- Medical Research Council (MRC) [MR/K022733/1]
- European Commission, FP7-PEOPLE-ITN [316882]
- Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's & St. Thomas' NHS Foundation Trust
- King's College London
- Wellcome Trust
- EPSRC [WT 088641/Z/09/Z]
- MRC [MR/K022733/1] Funding Source: UKRI
- Medical Research Council [MR/K022733/1] Funding Source: researchfish
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The receptor for advanced glycation endproducts (RAGE) is an ubiquitous, transmembrane, immunoglobulin-like receptor that exists in multiple isoforms and binds to a diverse range of endogenous extracellular ligands and intracellular effectors. Ligand binding at the extracellular domain of RAGE initiates a complex intracellular signaling cascade, resulting in the production of reactive oxygen species (ROS), immunoinflammatory effects, cellular proliferation, or apoptosis with concomitant upregulation of RAGE itself. To date, research has mainly focused on the correlation between RAGE activity and pathological conditions, such as cancer, diabetes, cardiovascular diseases, and neurodegeneration. Because RAGE plays a role in many pathological disorders, it has become an attractive target for the development of inhibitors at the extracellular and intracellular domains. This review describes the role of endogenous RAGE ligands/effectors in normo- and pathophysiological processes, summarizes the current status of exogenous small-molecule inhibitors of RAGE and concludes by identifying key strategies for future therapeutic intervention.
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