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Methylglyoxal, a Highly Reactive Dicarbonyl Compound, in Diabetes, Its Vascular Complications, and Other Age-Related Diseases.
Physiological Reviews ( IF 29.9 ) Pub Date : 2019-09-20 , DOI: 10.1152/physrev.00001.2019
C G Schalkwijk 1 , C D A Stehouwer 1
Affiliation  

The formation and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl compound, has been implicated in the pathogenesis of type 2 diabetes, vascular complications of diabetes, and several other age-related chronic inflammatory diseases such as cardiovascular disease, cancer, and disorders of the central nervous system. MGO is mainly formed as a byproduct of glycolysis and, under physiological circumstances, detoxified by the glyoxalase system. MGO is the major precursor of nonenzymatic glycation of proteins and DNA, subsequently leading to the formation of advanced glycation end products (AGEs). MGO and MGO-derived AGEs can impact on organs and tissues affecting their functions and structure. In this review we summarize the formation of MGO, the detoxification of MGO by the glyoxalase system, and the biochemical pathways through which MGO is linked to the development of diabetes, vascular complications of diabetes, and other age-related diseases. Although interventions to treat MGO-associated complications are not yet available in the clinical setting, several strategies to lower MGO have been developed over the years. We will summarize several new directions to target MGO stress including glyoxalase inducers and MGO scavengers. Targeting MGO burden may provide new therapeutic applications to mitigate diseases in which MGO plays a crucial role.

中文翻译:

甲基乙二醛,一种高反应性的二羰基化合物,在糖尿病,其血管并发症和其他与年龄有关的疾病中。

甲基乙二醛(MGO)(一种高反应性二羰基化合物)的形成和积累与2型糖尿病的发病机理,糖尿病的血管并发症以及其他一些与年龄有关的慢性炎性疾病(如心血管疾病,癌症和疾病)有关。中枢神经系统。MGO主要形成为糖酵解的副产物,在生理条件下,被乙二醛酶系统解毒。MGO是蛋白质和DNA的非酶糖基化的主要前体,随后导致高级糖基化终产物(AGEs)的形成。MGO和MGO衍生的AGE可影响器官和组织,影响其功能和结构。在这篇综述中,我们总结了MGO的形成,乙二醛酶系统对MGO的解毒作用,以及MGO与糖尿病的发展,糖尿病的血管并发症以及其他与年龄有关的疾病相关的生化途径。尽管在临床环境中尚无治疗MGO相关并发症的干预措施,但多年来已开发出多种降低MGO的策略。我们将总结针对MGO压力的几个新方向,包括乙二醛酶诱导剂和MGO清道夫。针对MGO的负担可能会提供新的治疗应用,以减轻MGO在其中发挥关键作用的疾病。我们将总结针对MGO压力的几个新方向,包括乙二醛酶诱导剂和MGO清道夫。针对MGO的负担可能会提供新的治疗应用,以减轻MGO在其中发挥关键作用的疾病。我们将总结针对MGO压力的几个新方向,包括乙二醛酶诱导剂和MGO清道夫。针对MGO的负担可能会提供新的治疗应用,以减轻MGO在其中发挥关键作用的疾病。
更新日期:2019-12-03
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