Advanced Glycation End-Products (AGEs): Receptors, Signalling Pathways, and Anti-AGE Therapies

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Carbohydrates".

Deadline for manuscript submissions: 31 March 2025 | Viewed by 5352

Special Issue Editors


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Guest Editor
Institute of Molecular and Industrial Biotechnology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 2/22, 90-537 Lodz, Poland
Interests: nutrigenomics, cell signaling, receptors, GPCR-receptors, chemistry and biochemistry of nucleic acids

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Guest Editor
Institute of Molecular and Industrial Biotechnology, Lodz University of Technology, Stefanowskiego 2/22, 90-537 Lodz, Poland
Interests: Stab2 receptor, advanced glycation end-products, protein-ligand interactions, structural biology, Stab2 receptor, advanced glycation end-products, psychrophilic enzymes

Special Issue Information

Dear Colleagues,

Advanced glycation end-products (AGEs) constitute a complex, chemically diverse group of biomolecules formed endogenously on the course of various pathways in the human body or absorbed exogenously from diet. They are formed non-enzymatically by condensation of the carbonyl group of reducing saccharides and the free amine group of nucleic acids, proteins, or lipids. Unstable intermediates are further rearranged, yielding a group of reactive carbonyls and irreversible, stable end-products. The most investigated examples of AGEs include Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), pentosidine, crossline, arginine pyrimidine, and others. Levels of specific glycated proteins, such as circulating glycated hemoglobin (HbA1c), serve as reliable biomarkers of adverse states like hyperglycemic states, insulin resistance, and diabetes mellitus (DM).

AGEs are recognized by several cellular receptors, including the Receptor for AGEs (RAGE), AGE-R1/OST-48, AGE-R2/80K-H, AGE-R3/galectin-3, and scavenger receptors (Stab1, Stab2, LOX1, CD36, SR-AI, SR-BI). The insight into structural aspects of AGE binding is minimal, and no receptor-ligand crystal structures are known. Only one solution NMR structure with CEL peptide for the primary receptor, RAGE, is currently available.

Upon binding to the receptor, AGEs trigger many signalling pathways related to inflammation and oxidative stress. The number of publications reporting the evidence of their involvement in many physiological and pathological processes is steadily growing. They have been implicated in several lifestyle-related diseases, including DM and its complications, cancer, renal, neurodegenerative, and cardiovascular diseases.

The strategies against the deleterious impact of AGEs rely either on natural products or synthetic compounds and can have diverse mechanisms of action. One of the approaches is the scavenging of AGEs; the others aim to block the receptors of these biomolecules or reduce their formation in the human body. Although many pharmacologic anti-AGE treatments have been recently reported, their efficacy remains to be evaluated in clinical trials.

The goal of this Special Issue is to collect experimental papers and reviews that enhance the understanding of AGE-receptor binding, the signalling pathways they activate, and anti-AGE therapies. We look forward to receiving your contributions.

Prof. Dr. Maria Koziołkiewicz
Dr. Aleksandra Twarda-Clapa
Guest Editors

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Keywords

  • advanced glycation end-products
  • AGEs, AGE receptors
  • anti-AGE therapies
  • RAGE
  • scavenger receptors
  • AGE-related diseases
  • signalling pathways

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Published Papers (2 papers)

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Review

24 pages, 1175 KiB  
Review
The RAGE Axis: A Relevant Inflammatory Hub in Human Diseases
by Armando Rojas, Cristian Lindner, Ivan Schneider, Ileana Gonzalez and Jaime Uribarri
Biomolecules 2024, 14(4), 412; https://doi.org/10.3390/biom14040412 - 28 Mar 2024
Cited by 4 | Viewed by 2483
Abstract
In 1992, a transcendental report suggested that the receptor of advanced glycation end-products (RAGE) functions as a cell surface receptor for a wide and diverse group of compounds, commonly referred to as advanced glycation end-products (AGEs), resulting from the non-enzymatic glycation of lipids [...] Read more.
In 1992, a transcendental report suggested that the receptor of advanced glycation end-products (RAGE) functions as a cell surface receptor for a wide and diverse group of compounds, commonly referred to as advanced glycation end-products (AGEs), resulting from the non-enzymatic glycation of lipids and proteins in response to hyperglycemia. The interaction of these compounds with RAGE represents an essential element in triggering the cellular response to proteins or lipids that become glycated. Although initially demonstrated for diabetes complications, a growing body of evidence clearly supports RAGE’s role in human diseases. Moreover, the recognizing capacities of this receptor have been extended to a plethora of structurally diverse ligands. As a result, it has been acknowledged as a pattern recognition receptor (PRR) and functionally categorized as the RAGE axis. The ligation to RAGE leads the initiation of a complex signaling cascade and thus triggering crucial cellular events in the pathophysiology of many human diseases. In the present review, we intend to summarize basic features of the RAGE axis biology as well as its contribution to some relevant human diseases such as metabolic diseases, neurodegenerative, cardiovascular, autoimmune, and chronic airways diseases, and cancer as a result of exposure to AGEs, as well as many other ligands. Full article
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15 pages, 1019 KiB  
Review
Structures of Toxic Advanced Glycation End-Products Derived from Glyceraldehyde, A Sugar Metabolite
by Akiko Sakai-Sakasai, Kenji Takeda, Hirokazu Suzuki and Masayoshi Takeuchi
Biomolecules 2024, 14(2), 202; https://doi.org/10.3390/biom14020202 - 8 Feb 2024
Cited by 6 | Viewed by 2174
Abstract
Advanced glycation end-products (AGEs) have recently been implicated in the onset/progression of lifestyle-related diseases (LSRDs); therefore, the suppression of AGE-induced effects may be used in both the prevention and treatment of these diseases. Various AGEs are produced by different biological pathways in the [...] Read more.
Advanced glycation end-products (AGEs) have recently been implicated in the onset/progression of lifestyle-related diseases (LSRDs); therefore, the suppression of AGE-induced effects may be used in both the prevention and treatment of these diseases. Various AGEs are produced by different biological pathways in the body. Glyceraldehyde (GA) is an intermediate of glucose and fructose metabolism, and GA-derived AGEs (GA-AGEs), cytotoxic compounds that accumulate and induce damage in mammalian cells, contribute to the onset/progression of LSRDs. The following GA-AGE structures have been detected to date: triosidines, GA-derived pyridinium compounds, GA-derived pyrrolopyridinium lysine dimers, methylglyoxal-derived hydroimidazolone 1, and argpyrimidine. GA-AGEs are a key contributor to the formation of toxic AGEs (TAGE) in many cells. The extracellular leakage of TAGE affects the surrounding cells via interactions with the receptor for AGEs. Elevated serum levels of TAGE, which trigger different types of cell damage, may be used as a novel biomarker for the prevention and early diagnosis of LSRDs as well as in evaluations of treatment efficacy. This review provides an overview of the structures of GA-AGEs. Full article
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