The biology of the receptor for advanced glycation end products and its ligands.

By A. Schmidt, Shiqiang Yan, S. Yan, David M. Stern. Biochimica et Biophysica Acta, 2000

725 citations recorded by the source corpus.

Receptor for advanced glycation end products (RAGE) is a multiligand member of the immunoglobulin superfamily of cell surface molecules whose repertoire of ligands includes advanced glycation end products (AGEs), amyloid fibrils, amphoterins and S100/calgranulins. The overlapping distribution of these ligands and cells overexpressing RAGE results in sustained receptor expression which is magnified via the apparent capacity of ligands to upregulate the receptor. We hypothesize that RAGE-ligand interaction is a propagation factor in a range of chronic disorders, based on the enhanced accumulation of the ligands in diseased tissues. For example, increased levels of AGEs in diabetes and renal insufficiency, amyloid fibrils in Alzheimer's disease brain, amphoterin in tumors and S100/calgranulins at sites of inflammation have been identified. The engagement of RAGE by its ligands can be considered the 'first hit' in a two-stage model, in which the second phase of cellular perturbation is mediated by superimposed accumulation of modified lipoproteins (in atherosclerosis), invading bacterial pathogens, ischemic stress and other factors. Taken together, these 'two hits' eventuate in a cellular response with a propensity towards tissue destruction rather than resolution of the offending pathogenic stimulus. Experimental data are cited regarding this hypothesis, though further studies will be required, especially with selective low molecular weight inhibitors of RAGE and RAGE knockout mice, to obtain additional proof in support of our concept.

Subfields: Clinical Biochemistry, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/11e633d8561ccdc645c657d2198c6ddd95668ede

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In Clinical Biochemistry

1. Andrzej Grzybowski
2. M. Nita
3. G. Tezel

In Molecular Biology

1. Andrzej Grzybowski
2. Stephan Beck
3. M. Nita
4. Ruth C. Lovering
5. G. Tezel

In Physiology

1. Andrzej Grzybowski
2. M. Nita
3. G. Tezel

Citations in the corpus

• Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences. (2006, background): “…to specific receptors; and depending on the cell type and concurrent signaling, receptormediated events result in cell activation/proliferation, chemotaxis, angiogenesis, generation of ROS, and/or apoptotic cell death (Neeper et al., 1992; Schmidt et al., 2000; Thornalley, 1998; Yan et al., 1996).”
• Advanced Glycation End Products and Diabetes Mellitus: Mechanisms and Perspectives (2022, background): “One of the salient features of the receptor is its capability to bind a broad repertoire of ligands [39,40].”
• The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults (2016, background): “As a consequence of AGEs accumulation, many proteins lose their function, including proteins involved in the regulation of gene transcription [97].”
• Advanced Glycation End-Products (AGEs): Formation, Chemistry, Classification, Receptors, and Diseases Related to AGEs (2022, background): “For example, interactions with the ABPP and S100B after myocardial infarction entangles this receptor also in atherosclerosis, cancer, and neurodegenerative diseases [77,78].”
• Periodontal disease: associations with diabetes, glycemic control and complications. (2008, background): “The receptor for AGEs, RAGE, is the principal signal transducer for the AGE ligand (Schmidt et al, 2000).”
• Gene map of the extended human MHC (2004, background): “Another gene — the product of which is probably involved in autoimmunity and inflammation — is AGER , which encodes the receptor for ADVANCED GLYCATION end product”