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

F1 (+/-)

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

Azeliragon

TTP-488, PF-4494700, PF-04494700

Discontinued

Vtv Therapeutics

Alzheimer Disease, Diabetic Nephropathies

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

TTP-4000

TTP-4000

Discontinued

Vtv Therapeutics

Alzheimer Disease

Tenilsetam

CAS-997

Discontinued

Sanofi

Dementia

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)