RAGE
Synonyms
Receptor for advanced glycosylation end products, AGER, Advanced Glycosylation End-Product Specific Receptor, RAGE, Receptor For Advanced Glycation End-Products Variant 20, Receptor For Advanced Glycation End-Products, RAGE Isoform NtRAGE-Delta, RAGE Isoform SRAGE-Delta, SCARJ1, Receptor for Advanced Glycation End Products, Advanced glycosylation end product-specific receptor
Description
RAGE (receptor for advanced glycation endproducts), also called AGER, is a 35 kilodalton transmembrane receptor of the immunoglobulin super family. It mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Receptor for amyloid beta peptide. Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons. ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space. Can also bind oligonucleotides.
KO Status
RenMab: F2 (-/-)
RenLite: F0
Drug Information
Drugs in clinical trials: 3
Latest Research Phase: Phase 3 Clinical
Drug Name
Code
Phase
Company
Indications
Clinical Trials
TRC-041266
TRC-041266
Phase 3 Clinical
Torrent Pharmaceuticals
Heart Failure
TRC-4186
TX-41XX, TRC-4186
Phase 2 Clinical
Torrent Pharmaceuticals
Heart Failure, Diabetes Complications
TTP-4000
TTP-4000
Discontinued
Vtv Therapeutics
Alzheimer Disease
Tenilsetam
CAS-997
Discontinued
Sanofi
Dementia
Alagebrium chloride
ALT-711
Discontinued
Synvista Therapeutics
Erectile Dysfunction, Heart Failure, Diastolic, Diabetes Mellitus, Type 1, Heart Failure, Hypertension, Dyspnea, Hypertrophy, Left Ventricular, Diabetic Nephropathies, Pulmonary Edema
Azeliragon
TTP-488, PF-4494700, PF-04494700
Discontinued
Vtv Therapeutics
Alzheimer Disease, Diabetic Nephropathies
References
Title
Authors
Source
Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins
Neeper M., Schmidt A.M., Brett J., Yan S.D., Wang F., Pan Y.C., Elliston K., Stern D., Shaw A.,
J. Biol. Chem. 267:14998-15004(1992)
Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3
Sugaya K., Fukagawa T., Matsumoto K., Mita K., Takahashi E., Ando A., Inoko H., Ikemura T.,
Genomics 23:408-419(1994)
Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury
Yonekura H., Yamamoto Y., Sakurai S., Petrova R.G., Abedin J., Li H., Yasui K., Takeuchi M., Makita Z., Takasawa S., Okamoto H., Watanabe T., Yamamoto H.,
Biochem. J. 370:1097-1109(2003)
Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse
Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L.,
Genome Res. 13:2621-2636(2003)
Identification, classification, and expression of RAGE gene splice variants
Hudson B.I., Carter A.M., Harja E., Kalea A.Z., Arriero M., Yang H., Grant P.J., Schmidt A.M.,
FASEB J. 22:1572-1580(2008)
Alternative splicing of the RAGE cytoplasmic domain regulates cell signaling and function
Jules J., Maiguel D., Hudson B.I.,
PLoS ONE 8:E78267-E78267(2013)
Complete sequencing and characterization of 21,243 full-length human cDNAs
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Sugano S.,
Nat. Genet. 36:40-45(2004)
The DNA sequence and analysis of human chromosome 6
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D., Beck S.,
Nature 425:805-811(2003)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)
The MGC Project Team,
Genome Res. 14:2121-2127(2004)
Effects of novel polymorphisms in the RAGE gene on transcriptional regulation and their association with diabetic retinopathy
Hudson B.I., Stickland M.H., Futers T.S., Grant P.J.,
Diabetes 50:1505-1511(2001)