Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune 412115, Maharashtra, India.
Department of Medical Laboratory Sciences, University of Hail, Hail City 2440, Saudi Arabia.
Glycobiology. 2022 Nov 22;32(12):1068-1088. doi: 10.1093/glycob/cwac060.
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.
糖基化是指还原糖的羰基与蛋白质的游离氨基发生缩合反应，形成美拉德产物和晚期糖基化终末产物（AGEs）。这些 AGEs 通过在带正电荷的精氨酸和赖氨酸残基上配置负电荷来改变蛋白质的结构和功能。糖基化在代谢性疾病、脑紊乱、衰老和肠道微生物失调的发病机制中起着至关重要的作用，其通过 3 种机制发挥作用：（i）形成高度反应性的代谢途径衍生的中间产物，这些中间产物直接影响细胞内蛋白质的功能；（ii）AGEs 与其相关受体的相互作用产生氧化应激，导致转录因子 NF-κB 的激活；（iii）细胞外 AGEs 的产生阻碍了细胞和基质分子之间的相互作用，影响血管和神经的发生。因此，需要采用各种治疗策略来抑制糖基化的不同步骤，例如阻断氨基和羰基、美拉德产物、AGEs-RAGE 相互作用、螯合过渡金属、清除自由基以及破坏 AGEs 形成的交联。本综述重点阐述了糖基化影响的分子机制在非传染性疾病的发生和治疗中的作用。
