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Receptor for advanced glycation end-products: Biological significance and imaging applications
Iwona T Dobrucki1,2,3,4, Angelo Miskalis1, Michael Nelappana1,2
1Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Abstract:
The receptor for advanced glycation end-products (RAGE or AGER) is a transmembrane, immunoglobulin-like receptor that, due to its multiple isoform structures, binds to a diverse range of endo- and exogenous ligands. RAGE activation caused by the ligand binding initiates a cascade of complex pathways associated with producing free radicals, such as reactive nitric oxide and oxygen species, cell proliferation, and immunoinflammatory processes. The involvement of RAGE in the pathogenesis of disorders such as diabetes, inflammation, tumor progression, and endothelial dysfunction is dictated by the accumulation of advanced glycation end-products (AGEs) at pathologic states leading to sustained RAGE upregulation. The involvement of RAGE and its ligands in numerous pathologies and diseases makes RAGE an interesting target for therapy focused on the modulation of both RAGE expression or activation and the production or exogenous administration of AGEs. Despite the known role that the RAGE/AGE axis plays in multiple disease states, there remains an urgent need to develop noninvasive, molecular imaging approaches that can accurately quantify RAGE levels in vivo that will aid in the validation of RAGE and its ligands as biomarkers and therapeutic targets. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Diagnostic Tools > Biosensing.
Insights
The receptor for advanced glycation end-products (RAGE) is implicated in various diseases. Developing noninvasive imaging to quantify RAGE levels in vivo is crucial for validating it as a therapeutic target.
Area of Science:
- Biomedical research
- Molecular imaging
- Diagnostic tools
Background:
- The receptor for advanced glycation end-products (RAGE) is a transmembrane receptor with diverse ligand-binding capabilities.
- RAGE activation triggers pathways involving free radicals, cell proliferation, and inflammation.
- Accumulation of advanced glycation end-products (AGEs) leads to RAGE upregulation in diseases like diabetes and cancer.
Purpose of the Study:
- To highlight the significance of the RAGE/AGE axis in various pathologies.
- To emphasize the urgent need for noninvasive in vivo molecular imaging techniques for RAGE.
- To support the validation of RAGE and its ligands as diagnostic biomarkers and therapeutic targets.
Main Methods:
- Review of existing literature on RAGE, its ligands, and associated pathologies.
- Discussion of the role of RAGE in disease pathogenesis.
- Exploration of therapeutic strategies targeting the RAGE/AGE axis.
Main Results:
- RAGE is involved in the pathogenesis of diabetes, inflammation, tumor progression, and endothelial dysfunction.
- The RAGE/AGE axis presents a promising target for therapeutic intervention.
- Current limitations in quantifying RAGE levels in vivo hinder therapeutic validation.
Conclusions:
- Noninvasive molecular imaging approaches are essential for in vivo RAGE quantification.
- Such imaging will aid in validating RAGE and its ligands as biomarkers and therapeutic targets.
- Advancements in nanodiagnostics and biosensing are critical for RAGE-targeted therapies.
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