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Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
12:50

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response

Published on: September 15, 2017

RAGE: therapeutic target and biomarker of the inflammatory response--the evidence mounts

Ravichandran Ramasamy1, Shi Fang Yan, Ann Marie Schmidt

  • 1Division of Surgical Science, Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA

Journal of Leukocyte Biology
|May 30, 2009
PubMed

Insights

The receptor for advanced glycation end products (RAGE) is implicated in chronic diseases. Blocking RAGE or using soluble RAGE (sRAGE) shows therapeutic potential and may serve as a disease biomarker.

Area of Science:

  • Molecular Biology
  • Immunology
  • Biochemistry

Background:

  • The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor involved in various chronic inflammatory diseases.
  • RAGE activation triggers signaling pathways linked to cellular migration and Rho GTPase activation (cdc42 and rac-1).

Purpose of the Study:

  • To explore the role of RAGE in chronic diseases.
  • To investigate the therapeutic potential of targeting RAGE.
  • To assess the utility of soluble RAGE (sRAGE) as a biomarker.

Main Methods:

  • Pharmacological blockade of RAGE.
  • Genetic deletion of RAGE in murine models.
  • Analysis of circulating soluble RAGE (sRAGE) levels in human subjects.

Main Results:

  • RAGE blockade or deletion significantly protected against murine models of diabetes, inflammation, Alzheimer's disease, and tumors.
  • Soluble RAGE (sRAGE) variants, including esRAGE, are found in human plasma.
  • Plasma sRAGE levels appear to correlate with RAGE-associated diseases.

Conclusions:

  • RAGE is a viable therapeutic target for multiple chronic diseases.
  • Plasma sRAGE levels may serve as a novel biomarker for monitoring disease progression and treatment response in chronic inflammatory conditions.

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