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Cited by 691

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

Open access
Schmidt, Ann Marie, Yan, Shi Du, Yan, Shi Fang, Stern, David M.·2000·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Abstract

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.

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Metadata

Authors
Schmidt, A. M., Yan, S. D., Yan, S. F., & Stern, D. M.
Venue
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Publisher
Elsevier BV
Published
2000-12
Volume
1498
Issue
2-3
Pages
99-111
ISSN
0167-4889 (ISSN-L)
OpenAlex
W2104938297
Cited by
691
References
6
FWCI
10.41
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: The biology of the receptor for advanced glycation end products and its ligands. https://app.cochat.ai/papers/10.1016/s0167-4889(00)00087-2
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Schmidt, A. M., Yan, S. D., Yan, S. F., & Stern, D. M. (2000). The biology of the receptor for advanced glycation end products and its ligands. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. https://doi.org/10.1016/s0167-4889(00)00087-2

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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.