Genetic Deficiency Of Neuronal RAGE Protects Against AGEs-induced Synaptic Injury

Synaptic degeneration is an early pathological feature of aging and age-related diseases including Alzheimer’s disease (AD). AGEs accumulation was associated with Aging, via proteins or lipids, non enzymatic glycation (or oxidation) after reaction to form primary products, at last, accumulated to be AGEs. AGE formation is accelerated in diabetes and AD-affected brain, Especially for diabetic patients, AD, blood glucose levels remain high and neural degeneration accelerate AGEs formation, affects brain and nervous system, leading to cell dysfunction. Receptor for advanced glycation end products (RAGE) are members of the super family of cell surface molecules of the Ig. RAGE (AGEs receptors), it’s members of the super family of cell surface molecules of the immunoglobulin, is also widely studied, AGEs interacts with RAGE, cause a variety of diseases.Here, we analyze the contribution of neuronal receptor of AGEs (RAGE) signaling to AGEs-mediated synaptic injury using novel transgenic neuronal RAGE knockout mice specifically targeted to the cortex. By the following methods:(1) Electrophysiology(LTP) to record CA1of hippocampus;(2) localization of tissue or cell via antigen antibody reaction, determined by confocal microscope;(3)by means of the corresponding protein chromatography (such as P38, ERK, GSK, JNK). Results of the different characterization methods is matched. Obviously, we can be sure: AGEs receptor (RAGE) deletion, can avoid AGEs damaging LTP and reducing the number of synapses. In addition, we also tried a variety of related proteins (P38, ERK, GSK, JNK etc.) and inhibitors, further, make sure that the P38protein plays a mediated role in synaptic damage by AGEs.These data show that neuronal RAGE functions as a signal transducer for AGEs-induced synaptic’s dysfunction. Therefore, the AGEs-RAGE combinnation contributes to synaptic injury via the p38MAP kinase signal transduction pathway. So, RAGE blockade may be a target in aging and age-related neurodegenerative diseases.