Therapeutic Potential of DNA-aptamers Raised Against AGE-RAGE Axis in Diabetes-related Complications

Abstract

Accumulating evidence has indicated that formation and accumulation of advanced glycation end products (AGEs) progress under diabetic conditions, thereby contributing to the development and progression of various diabetes- and aging-related disorders, such as diabetic nephropathy, diabetic retinopathy, atherosclerotic cardiovascular disease, insulin resistance, cancer growth and metastasis, osteoporosis, and Alzheimer’s disease. Modification of proteins, lipids and nucleic acids by AGEs alter their structural integrity and function, and evoke oxidative stress generation and inflammatory reactions through the interaction with a receptor for AGEs (RAGE), being involved in the above-mentioned devastating disorders. These observations suggest that inhibition of the AGE-RAGE axis is a novel therapeutic target for diabetes- and aging-related complications. Aptamers are short single-stranded RNA or DNA oligonucleotides that can bind to numerous types of proteins with high specificity and affinity, and some type of aptamer raised against vascular endothelial growth factor has been approved for the treatment of patients with neovascular age-related macular degeneration. Since aptamers can be easily generated and highly penetrated into various organs with a low risk of allergic reactions, they may be superior to antibodies for neutralizing and/or blocking target proteins or cell surface receptors. Therefore, in this review, we describe the therapeutic potential of DNA-aptamers raised against the AGE-RAGE axis in diabetes-associated complications, especially focusing on vascular complications of diabetes and cancer.