AGE proteins as a causative factor in Alzheimer's Disease

Authors

Abstract

The reaction between reducing sugars and protein free amines, known as the Maillar reaction results in the formation of advanced glycation endproducts (AGEs). AGE modification changes the structure of proteins to amyloid cross-beta structure. These protein structures can activate receptors known as RAGE on glial cells (microglia and astrocytes), and induce the expression of inducible nitric oxide synthase (iNOS). Activation of inducible nitric oxide synthase in glial cells is assumed to contribute to oligodendrocyte degeneration in demyelinating diseases (e.g. multiple sclerosis) and neuronal death during Alzheimer’s Disease (AD). Our goal was to study AGE-activated signal transduction pathways involved in the induction of iNOS in the rat microglial cells. In vitro prepared AGE-BSA used as model AGE, induces nitric oxide (NO). We treated the Cultured Microglial cell with different range of glycated BSA (low-glycated-BSA to Advanced Glycated End-BSA) and BSA which conserved against glycation in the presence of some antiglycation agents. So, after we characterized the effects of these treatments on the activation of iNOS in microglia and on microglial cell proliferation and morphology. Secreted Nitric Oxide was determined spectrophotometrically by using the Griess reaction. According to our result we found that AGE-BSA increase the iNOS expression and NO secretion which can lead to AD, but BSA which was conserved against glycation couldn’t induce NO production in microglial cells.