Understanding the role of glycation in the pathology of various non-communicable diseases along with novel therapeutic strategies

Abstract

Glycation refers to carbonyl group condensation of the reducing sugar with the free amino group of protein, which forms Amadori products and advanced glycation end products (AGEs). These AGEs alter protein structure and function by configuring a negative charge on the positively charged arginine and lysine residues. Glycation plays a vital role in the pathogenesis of metabolic diseases, brain disorders, aging, and gut microbiome dysregulation with the aid of 3 mechanisms: (i) formation of highly reactive metabolic pathway-derived intermediates, which directly affect protein function in cells, (ii) the interaction of AGEs with its associated receptors to create oxidative stress causing the activation of transcription factor NF-κB, and (iii) production of extracellular AGEs hinders interactions between cellular and matrix molecules affecting vascular and neural genesis. Therapeutic strategies are thus required to inhibit glycation at different steps, such as blocking amino and carbonyl groups, Amadori products, AGEs-RAGE interactions, chelating transition metals, scavenging free radicals, and breaking crosslinks formed by AGEs. The present review focused on explicitly elaborating the impact of glycation-influenced molecular mechanisms in developing and treating noncommunicable diseases.