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.

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.

Related Concept Videos

Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
2.5K
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.2K
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
12.2K
Spare Receptors01:30

Spare Receptors

Some receptors remain unoccupied even when an agonist produces a maximal response. Such empty ones are called spare receptors. In presence of spare receptors the maximum effect of an agonist drug is achieved with fewer than 100% of the receptors being occupied. To determine the presence of spare receptors, scientists often compare the concentration of the drug needed to produce 50% of the maximum effect (EC50) with the concentration of the drug needed to occupy 50% of the receptors (Kd). If the...
3.6K