Receptor for advanced glycation end‐products: Biological significance and imaging applications

Abstract

The receptor for advanced glycation end‐products (RAGE or AGER) is a transmembrane, immunoglobulin‐like receptor that, due to its multiple isoform structures, binds to a diverse range of endo‐ and exogenous ligands. RAGE activation caused by the ligand binding initiates a cascade of complex pathways associated with producing free radicals, such as reactive nitric oxide and oxygen species, cell proliferation, and immunoinflammatory processes. The involvement of RAGE in the pathogenesis of disorders such as diabetes, inflammation, tumor progression, and endothelial dysfunction is dictated by the accumulation of advanced glycation end‐products (AGEs) at pathologic states leading to sustained RAGE upregulation. The involvement of RAGE and its ligands in numerous pathologies and diseases makes RAGE an interesting target for therapy focused on the modulation of both RAGE expression or activation and the production or exogenous administration of AGEs. Despite the known role that the RAGE/AGE axis plays in multiple disease states, there remains an urgent need to develop noninvasive, molecular imaging approaches that can accurately quantify RAGE levels in vivo that will aid in the validation of RAGE and its ligands as biomarkers and therapeutic targets.This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Diagnostic Tools > Biosensing

The RAGE Axis: A Relevant Inflammatory Hub in Human Diseases

“…It is noteworthy that emerging studies have demonstrated the potential of the RAGE axis in the multimodality imaging diagnostic of inflammatory diseases. In this sense, non-invasive imaging detection of RAGE by positron emission tomography (PET) and single-photon emission computed tomography (SPECT) may allow for early detection and surveillance of RAGE-related pathologies [213,214], which could influence the diagnosis and therapeutic management of different diseases [215,216].…”

Methylglyoxal and Advanced Glycation End Products (AGEs): Targets for the Prevention and Treatment of Diabetes-Associated Bladder Dysfunction?

“…RAGE plays an important role in the innate immune response and as a mediator of proinflammatory processes, triggering multiple intracellular signaling pathways, including the generation of proinflammatory mediators such as IL-1β, VCAM-1, and TNF-α via the transcription factor NF-κB [138] and phosphorylation of JNK and p38MAPK [141]. Furthermore, many of the RAGE actions have been attributed to the activation of NADPH oxidase [142], which leads to excess formation of ROS, thus contributing to generate a pro-oxidant environment [143][144][145]. Figure 1 illustrates the MGO-AGEs-RAGE signaling and glyoxalase system (Glo1 and Glo2 enzymes).…”