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AGE/RAGE signalling regulation by miRNAs: Associations with diabetic complications and therapeutic potential
Institution:1. Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China;2. Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology Mesra, Ranchi, India;3. Institute of Primate Research, Nairobi, Kenya;4. School of Life Science and Technology, China Pharmaceutical University, Nanjing, China;5. Department of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC;6. Department of Medical Coding Analysis - Emblem Health, Cognizant Technology Solutions India Pvt Ltd., Bangalore, India;1. Department of Biological Chemistry – Cellular and Molecular Biomechanics Unit, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;2. Department of Orthodontics, Dental School, National and Kapodistrian University of Athens, 11527, Athens, Greece
Abstract:Excessive formation of advanced glycation end-products (AGEs) presents the most important mechanism of metabolic memory that underlies the pathophysiology of chronic diabetic complications. Independent of the level of hyperglycaemia, AGEs mediate intracellular glycation of the mitochondrial respiratory chain proteins leading to excessive production of reactive oxygen species (ROS) and amplification of their formation. Additionally, AGEs trigger intracellular damage via activation of the receptor for AGEs (RAGE) signalling axis that leads to elevation of cytosolic ROS, nuclear factor kappaB (NF-κB) activation, increased expression of adhesion molecules and cytokines, induction of oxidative and endoplasmic reticulum stress. Recent studies have identified novel microRNAs (miRNAs) involved in the regulation of AGE/RAGE signalling in the context of diabetic micro- and macrovascular complications. The aim of this review is to discuss the emerging role of miRNAs on AGE/RAGE pathway and the potential use of several miRNAs as novel therapeutic targets.
Keywords:AGE/RAGE signalling  MiRNAs  Diabetes  Therapy
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