Effect of glycated proteins and inhibitory compounds intervening with the AGE-RAGE pathway on macrophages

Abstract

Glycation is a specific type of protein modification in ageing. The reaction of reducing sugar with a primary amino group is the most common nonenzymatic modification of proteins. Subsequent rearrangement, oxidation and dehydration yield a heterogeneous group of mostly coloured and fluorescent compounds, termed “Maillard products” or “advanced glycation end products (AGEs)”. AGEs are thought to play a role in the aetiology of various age-related diseases such as diabetes mellitus (DM) and Alzheimer's disease (AD). AD is a multifactorial disease, in which the rate of synapse loss and neuronal cell death determines the onset and/or progression of dementia. Activation of microglia and astrocytes with subsequent oxidative stress and cytokine release may be an important progression factor for AD. It is also suggested that the receptor for advanced glycation end products (RAGE) ligands-AGEs interaction might be another cause of glial activation, cytokine and reactive oxygen species (ROS) release. Different antioxidants, receptor mediated compounds and ROS scavenging enzymes might be able to intervene with the AGE-RAGE signalling pathway and slow down the progression of AD. The aim of this study is to investigate the effect of different compounds of antioxidants, receptor mediated compounds and ROS scavenging enzymes on inflammation induced by glycated proteins and to explore the suggested AGE-RAGE signalling pathway by examining inhibition of different parts of the signalling network