Department of Biology, College of Sciences, University of Hail, Hail, Saudi Arabia.
Department of Biochemistry, College of Medicine, University of Hail, Hail, Saudi Arabia.
Curr Protein Pept Sci. 2020;21(9):846-859. doi: 10.2174/1389203721666200505101734.
Glycation refers to the covalent binding of sugar molecules to macromolecules, such as DNA, proteins, and lipids in a non-enzymatic reaction, resulting in the formation of irreversibly bound products known as advanced glycation end products (AGEs). AGEs are synthesized in high amounts both in pathological conditions, such as diabetes and under physiological conditions resulting in aging. The body's anti-glycation defense mechanisms play a critical role in removing glycated products. However, if this defense system fails, AGEs start accumulating, which results in pathological conditions. Studies have been shown that increased accumulation of AGEs acts as key mediators in multiple diseases, such as diabetes, obesity, arthritis, cancer, atherosclerosis, decreased skin elasticity, male erectile dysfunction, pulmonary fibrosis, aging, and Alzheimer's disease. Furthermore, glycation of nucleotides, proteins, and phospholipids by α-oxoaldehyde metabolites, such as glyoxal (GO) and methylglyoxal (MGO), causes potential damage to the genome, proteome, and lipidome. Glyoxalase-1 (GLO-1) acts as a part of the anti-glycation defense system by carrying out detoxification of GO and MGO. It has been demonstrated that GLO-1 protects dicarbonyl modifications of the proteome and lipidome, thereby impeding the cell signaling and affecting age-related diseases. Its relationship with detoxification and anti-glycation defense is well established. Glycation of proteins by MGO and GO results in protein misfolding, thereby affecting their structure and function. These findings provide evidence for the rationale that the functional modulation of the GLO pathway could be used as a potential therapeutic target. In the present review, we summarized the newly emerged literature on the GLO pathway, including enzymes regulating the process. In addition, we described small bioactive molecules with the potential to modulate the GLO pathway, thereby providing a basis for the development of new treatment strategies against age-related complications.
糖基化是指糖分子与大分子（如 DNA、蛋白质和脂质）在非酶反应中发生共价结合，导致不可逆结合产物（称为晚期糖基化终末产物，AGEs）的形成。在病理条件下（如糖尿病）和生理条件下（导致衰老），大量合成 AGEs。体内的抗糖基化防御机制在去除糖基化产物方面起着关键作用。然而，如果这个防御系统失效，AGEs 开始积累，导致病理状况。研究表明，AGEs 的积累增加作为多种疾病的关键介质，如糖尿病、肥胖症、关节炎、癌症、动脉粥样硬化、皮肤弹性下降、男性勃起功能障碍、肺纤维化、衰老和阿尔茨海默病。此外，α-氧代醛代谢物（如乙二醛（GO）和甲基乙二醛（MGO））使核苷酸、蛋白质和磷脂糖化，对基因组、蛋白质组和脂质组造成潜在损害。糖基化酶-1（GLO-1）作为抗糖基化防御系统的一部分，通过对 GO 和 MGO 进行解毒作用。已经证明 GLO-1 可以保护蛋白质组和脂质组的二羰基修饰，从而阻碍细胞信号转导并影响与年龄相关的疾病。它与解毒和抗糖基化防御的关系已经得到很好的证实。MGO 和 GO 对蛋白质的糖化导致蛋白质错误折叠，从而影响其结构和功能。这些发现为 GLO 途径的功能调节可以作为一种潜在的治疗靶点提供了依据。在本综述中，我们总结了 GLO 途径的新出现文献，包括调节该过程的酶。此外，我们还描述了具有调节 GLO 途径潜力的小分子生物活性物质，为开发针对与年龄相关的并发症的新治疗策略提供了依据。
