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Zaher Merhi, Advanced Glycation End-Products: Pathway of Potentially Significant Pathophysiological and Therapeutic Relevance for Metabolic Syndrome in Menopausal Women, The Journal of Clinical Endocrinology & Metabolism, Volume 99, Issue 4, 1 April 2014, Pages 1146–1148, https://doi.org/10.1210/jc.2013-4465
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Advanced glycation end-products (AGEs) are usually formed slowly under physiological conditions. The accumulation of AGEs increases with variable pathologies such as type 2 diabetes, cardiovascular disease (CVD), and aging (1, 2). The effect of AGEs is classified as receptor-independent (such as cross-links with extracellular matrix) or receptor-dependent. The binding of AGEs to the cellular receptor (receptor for AGE [RAGE]) activates members of the MAPK family of signal transduction effectors, including p44/42 MAPK, c-Jun N-terminal kinases MAPK, and p38 MAPK. Furthermore, AGE-RAGE interaction stimulates activation of p21ras, Janus kinase/signal transducer and activator of transcription pathways, cdc42 and rac-1, Akt, and glycogen synthase kinase-3β signaling. These signaling pathways converge on multiple transcription factors such as early growth response-1, nuclear factor-κB (NF-κB), and cyclic AMP response element-binding protein, which mediate alterations in cell fate, migration, and production of inflammatory and profibrotic mediators by increasing expression of cytokines, chemokines, and adhesion molecules. On the other hand, the binding of AGEs to the soluble receptor (sRAGE) prevents the adverse intracellular events of the AGE-RAGE system (2).
