Related Experiment Videos
Receptor for advanced glycation endproducts: a multiligand receptor magnifying cell stress in diverse pathologic
David Stern1, Shi Du Yan, Shi Fang Yan
1Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. dstern@mail.mcg.edu
Abstract:
Receptor for Advanced Glycation Endproducts (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules capable of interacting with a broad spectrum of ligands, including advanced glycation endproducts (AGEs), amyloid fibrils, S100/calgranulins and amphoterin. The biology of RAGE is dictated by the accumulation of these ligands at pathologic sites, leading to upregulation of the receptor and sustained RAGE-dependent cell activation eventuating in cellular dysfunction. Although RAGE is not central to the initial pathogenesis of disorders in which it ultimately appears to be involved, such as diabetes, amyloidoses, inflammatory conditions and tumors (each of these conditions leading to accumulation of RAGE ligands), the receptor functions as a progression factor driving cellular dysfunction and exaggerating the host response towards tissue destruction, rather than restitution of homeostasis. These observations suggest that RAGE might represent a therapeutic target in a diverse group of seemingly unrelated disorders linked only by a multiligand receptor with an unusually wide and diverse repertoire of ligands, namely, RAGE.
Insights
The Receptor for Advanced Glycation Endproducts (RAGE) acts as a progression factor in various diseases. Targeting RAGE offers a therapeutic strategy for conditions linked by its diverse ligand interactions.
Area of Science:
- Cellular biology
- Immunology
- Pathology
Background:
- Receptor for Advanced Glycation Endproducts (RAGE) is an immunoglobulin superfamily cell surface receptor.
- RAGE binds diverse ligands like AGEs, amyloid fibrils, and S100 proteins.
- Ligand accumulation at pathologic sites upregulates RAGE, causing sustained cell activation and dysfunction.
Purpose of the Study:
- To elucidate the role of RAGE in disease pathogenesis.
- To explore RAGE as a potential therapeutic target.
Main Methods:
- Review of RAGE biology and ligand interactions.
- Analysis of RAGE involvement in various disease contexts.
Main Results:
- RAGE is upregulated in conditions like diabetes, amyloidosis, inflammation, and tumors due to ligand accumulation.
- RAGE functions as a progression factor, driving cellular dysfunction and tissue destruction.
- RAGE is not central to initial pathogenesis but exacerbates host response.
Conclusions:
- RAGE acts as a common link in diverse, seemingly unrelated disorders.
- Targeting RAGE presents a potential therapeutic strategy for multiple diseases.