34 Figure 2 Different splice variants of Advanced Glycation End Products TGX-221 cell line Receptor (RAGE)

in human brain: FL (full length Rage)-RAGE, Nt (N-terminal truncated)-RAGE, Es (Endogenous Secretary)-RAGE and s (soluble)-RAGE. The arrows show the deleted parts of sRAGE and … In addition, s-RAGE can suppress the RAGE signalling, and the administration of s-RAGE was shown to suppresses tumor growth and autoimmune Inhibitors,research,lifescience,medical response in animal models for cancer and multiple sclerosis suppresses.35 The s-RAGE plasma level is lower in patients with cognitive impairment, non-alcoholic fatty liver disease or type 2 diabetic in comparison with the control.30,31 Soluble-RAGE: a Marker and a Treatment Soluble-RAGE is the extracellular ligand binding domain of RAGE. It flows in the human plasma and has the potential to function as a decoy for Inhibitors,research,lifescience,medical RAGE signalling pathway by binding to circularising plasma AGEs. It has been suggested that s-RAGE can be a biomarker for RAGE-mediated disease development, especially vascular diseases.36 There are controversial studies regarding the s-RAGE plasma level and its relationship to the development of diseases. Some studies showed low s-RAGE plasma level Inhibitors,research,lifescience,medical and high N-carboxymethyllysine

levels, and abundant natural AGEs in diabetic patients with severe complications.37 On the other hand, the s-RAGE plasma levels are lower in patients Inhibitors,research,lifescience,medical with arthritis and hypertension in comparison with healthy patients.38 Yamagishi et al,39 reported a positive relationship between plasma level of AGEs and s-RAGE in non-diabetic population. Interestingly, one study reported

the elevated plasma levels of s-RAGE in septic patients. The study was the only to report high s-RAGE plasma levels in acute and non-chronic diseases.40 It was proposed that the s-RAGE plasma level was negatively correlated with body mass index , as overweight people with higher BMI had a lower s-RAGE plasma level.41 Remarkably, higher s-RAGE positively correlates with an increase in inflammatory markers Inhibitors,research,lifescience,medical such as tumor necrosis factor -α and monocyte chemo attractant protein-1 in patients with type-2 diabetes.42 The decoy characteristic of s-RAGE is not completely known to function as a negative feedback, as a biomarker, or as a protective factor, which acts by increasing the AGEs level in plasma in different MRIP diseases. Recombinant s-RAGE administration was tested in the animal model of DM with atherosclerotic lesions, and was shown to suppress the development of these lesions in the apo E null mice diabetic model.43 In another study, the administration of s-RAGE to diabetic C57/BJ6 and RAGE-transgenic mice with diabetic symptoms inhibited blood-retinal barrier breakdown and leukostasis, which are the signs of retinopathy in diabetic patients.44 These studies suggested an anti-ageing characteristic for s-RAGE in ageing-related diseases.