Non-enzymatic glycation and oxidative stress in chronic disease and diabetes mellitus

New approaches in biochemistry and molecular biology have increased the kno wledge on the pathophysiology of chronic diseases as late diabetic complica tions, Alzheimer's disease, arteriosclerosis and vascular disease by defini ng the concept of "AGE-formation and oxidative stress". Nonenzymatic glycation, in which reducing sugars are covalently bound to fr ee aminogroups of macromolecules, results in the formation of Advanced Glyc ation End products (AGEs) which accumulate during aging and at accelerated rate during the course of diabetes. Glycation accompanying oxidation proces ses support AGE-formation. AGE-formation changes the physicochemical proper ties 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 intracellu lar oxidative stress, which results in activation of the transcription fact or NF-kappa B and subsequent gene expression, which might be relevant in la te diabetic complications. Conclusion: Knowledge of the basic molecular mechanisms allows to understan d the interplay of different inducers such as radicals, cytokines, AGE-prot eins and amyloid-beta-peptids and to define oxidative stress as a "common e ndpoint" of cell dysfunction. With respect to therapeutic options it is now possible not only to optimize blood glycemic control, but also to design d rugs such as AGE-inhibitors and AGE-"cross-link" breakers. In addition pati ents with chronic disease associated with increased oxidative stress may be nefit from an antioxidant rich (and AGE protein poor?) nutrition.