Nawroth P P, Bierhaus A, Vogel G E, Hofmann M A, Zumbach M, Wahl P, Ziegler R
Abteilung Innere Medizin I, Endokrinologie und Stoffwechsel, Universität Heidelberg.
Med Klin (Munich). 1999 Jan 15;94(1):29-38. doi: 10.1007/BF03044692.
New approaches in biochemistry and molecular biology have increased the knowledge on the pathophysiology of chronic diseases as late diabetic complications, Alzheimer's disease, arteriosclerosis and vascular disease by defining the concept of "AGE-formation and oxidative stress." Nonenzymatic glycation, in which reducing sugars are covalently bound to free aminogroups of macromolecules, results in the formation of Advanced Glycation End products (AGEs) which accumulate during aging and at accelerated rate during the course of diabetes. Glycation accompanying oxidation processes support AGE-formation. AGE-formation changes the physicochemical properties of proteins, lipids and nucleic acids. In addition, binding of AGEs to specific surface receptors induces cellular signalling and cell activation. Interaction of AGEs with one of the receptors, RAGE, generates intracellular oxidative stress, which results in activation of the transcription factor NF-kappa B and subsequent gene expression, which might be relevant in late diabetic complications.
Knowledge of the basis molecular mechanisms allows to understand the interplay of different inducers such as redicals, cytokines, AGE-proteins and amyloid-beta-peptids and to define oxidative stress as a "common endpoint" of cell dysfunction. With respect to therapeutic options it is now possible not only to optimize blood glycemic control, but also to design drugs such as AGE-inhibitors and AGE-"cross-link" breakers. In addition patients with chronic disease associated with increased oxidative stress ay benefit from an antioxidant rich (and AGE protein poor?) nutrition.
生物化学和分子生物学的新方法通过定义“晚期糖基化终末产物（AGE）形成与氧化应激”的概念，增加了我们对诸如糖尿病晚期并发症、阿尔茨海默病、动脉硬化和血管疾病等慢性疾病病理生理学的认识。非酶糖基化是指还原糖与大分子的游离氨基共价结合，导致晚期糖基化终末产物（AGEs）的形成，这些产物在衰老过程中积累，并在糖尿病病程中加速积累。伴随氧化过程的糖基化促进AGE的形成。AGE的形成改变了蛋白质、脂质和核酸的物理化学性质。此外，AGEs与特定表面受体的结合会诱导细胞信号传导和细胞激活。AGEs与其中一种受体RAGE的相互作用会产生细胞内氧化应激，从而导致转录因子NF-κB的激活和随后的基因表达，这可能与糖尿病晚期并发症有关。
对基础分子机制的了解有助于理解自由基、细胞因子、AGE蛋白和β-淀粉样肽等不同诱导剂之间的相互作用，并将氧化应激定义为细胞功能障碍的“共同终点”。就治疗选择而言，现在不仅可以优化血糖控制，还可以设计诸如AGE抑制剂和AGE“交联”破坏剂等药物。此外，患有与氧化应激增加相关的慢性疾病的患者可能会从富含抗氧化剂（且AGE蛋白含量低？）的营养中受益。
