Advanced glycation end products pathway (AGE pathway)

The Advanced Glycation End products (AGE) pathway is a biochemical cascade initiated by the non-enzymatic reaction between reducing sugars and amino groups on proteins, lipids, or nucleic acids, known as the Maillard reaction [1]. This process results in the formation of stable, irreversible cross-linked adducts (AGEs) that accumulate in tissues over time, particularly under conditions of hyperglycemia and oxidative stress [1, 3]. These AGEs exert pathological effects by directly altering the structural properties of the extracellular matrix or by binding to the Receptor for Advanced Glycation End products (RAGE), a transmembrane protein of the immunoglobulin superfamily [1]. Activation of RAGE triggers intracellular signaling pathways, such as NF-κB and MAPK, leading to the production of reactive oxygen species (ROS) and pro-inflammatory cytokines [3]. The AGE-RAGE axis is a central driver in the development of diabetic complications, including nephropathy and retinopathy, and is also implicated in atherosclerosis, Alzheimer's disease, and the general aging process [1, 4]. Therapeutic strategies targeting this pathway include inhibitors of AGE formation, agents that break existing cross-links, and RAGE antagonists designed to block downstream inflammatory signaling [1, 2]. [1] Singh VP, et al. (2014). J Diabetes Res. doi:10.1155/2014/273908. [2] Prasad K. (2012). Clin Biochem. doi:10.1016/j.clinbiochem.2012.01.016. [3] Teissier T, Boulanger E. (2019). Ageing Res Rev. doi:10.1016/j.arr.2019.01.009. [4] ClinicalTrials.gov. (2023). NCT02080364 (Azeliragon).

Other names

AGE-RAGE signaling pathwayMaillard reaction pathwayGlycation pathwayAGE-RAGE axis

Inhibition of the non-enzymatic glycation process, chemical breaking of established AGE-protein cross-links, and pharmacological antagonism of the Receptor for Advanced Glycation End products (RAGE) [1, 3].