AGER

AGER Full Name

advanced glycosylation end product-specific receptor

AGER Introduction

The advanced glycosylation end product (AGE) receptor encoded by this gene is a member of the immunoglobulin superfamily of cell surface receptors. It is a multiligand receptor, and besides AGE, interacts with other molecules implicated in homeostasis, development, and inflammation, and certain diseases, such as diabetes and Alzheimer's disease. Many alternatively spliced transcript variants encoding different isoforms, as well as non-protein-coding variants, have been described for this gene .

Figure. AGER active infection events.(Source:Roy D, et al, 2018)

AGER was initially considered as a receptor for advanced glycation end products (AGEs). AGEs are produced by non enzymatic glycation of free nutrients such as glucose and galactose in the normal body, and their levels continue to increase with age. They are considered one of the signs of aging in the body. However, an increasing number of studies have shown that AGER can not only bind specifically to AGEs, but also to ligands such as HMGB1, S100, and A β, indicating that RAGE recognizes a molecular pattern rather than a simple sequence. Therefore, it is believed that RAGE is a new pattern recognition receptor that plays an important role in the occurrence and development of many diseases. The human AGER encoding gene is located on chromosome 6 and contains 11 exons and 10 shorter introns. No other subtypes of RAGE have been found in the human body yet. There are binding sites on the 5 'non coding region gene sequence of RAGE that bind to NF - κ B, SP1, AP1, Ets-1, HIF-1, Egr-1, and regulate RAGE transcription through these factors. The polyadenylation in the 3 'non coding region varies greatly and regulates the stability of AGER. In addition, the transcription of AGER is also affected by different splicing.

RAGE is low expressed in normal tissues, but significantly up-regulated in chronic inflammation, diabetes and other pathological conditions. Its signal transduction relies on the activation of transcription factors such as NF - κ B, and the extracellular domain is cleaved by proteases to form soluble RAGE (sRAGE) that participates in ligand transport. It has been confirmed that this receptor drives the pathological process by mediating metabolic inflammation, oxidative stress and other mechanisms in Alzheimer's disease, atherosclerosis, tumors and lung diseases. The development of RAGE, including sRAGE competitive inhibitors, antibody drugs and small molecule blockers, has shown therapeutic potential in diabetes complications and gynecological cancer models. The RAGE produced by the human RAGEmRNA codon generally consists of 404 amino acids, with a short intracellular domain, a transmembrane domain, and an extracellular domain consisting of three immunoglobulin like domains (V, C1, C2). The intracellular structural domain does not have any sequences homologous to any previously discovered signal regions. Conserved cysteine residues in Ig like structures can form disulfide bonds. RAGE bound to the membrane can form a soluble extracellular domain under protease degradation. This extracellular domain exists in the extracellular space or in vesicles within the cell, and is widely involved in the transport of A β in Alzheimer's disease.

Alternate Names for AGER

AGER; advanced glycosylation end product-specific receptor; RAGE; RAGE isoform sRAGE-delta; RAGE isoform NtRAGE-delta; receptor for advanced glycation end-products variant 20;

• 1.Roy D, Ramasamy R, Schmidt AM. Journey to a receptor for advanced glycation end products connection in severe acute respiratory syndrome coronavirus 2 infection: with stops along the way in the lung, heart, blood vessels, and adipose tissue. Arteriosclerosis, thrombosis, and vascular biology. 2021, 41(2):614-27.