Md Shofiul Azam1, Md Wahiduzzaman2, Md Reyad-Ul-Ferdous3, Md Nahidul Islam4, Mukta Roy5. 1. Department of Chemical and Food Engineering, Dhaka University of Engineering & Technology, Gazipur, 1707, Bangladesh. shofiul@duet.ac.bd. 2. Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. 3. Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Shandong University, Jinan, 250021, Shandong, China. 4. Department of Agro-Processing, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, 1706, Bangladesh. 5. Department of Food Engineering and Tea Technology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh.
Abstract
PURPOSE: This review aims to provide a precise perceptive of the insulin-degrading enzyme (IDE) and its relationship to type 2 diabetes (T2D), Alzheimer's disease (AD), obesity, and cardiovascular diseases. The purpose of the current study was to provide clear idea of treating prevalent diseases such as T2D, and AD by molecular pharmacological therapeutics rather than conventional medicinal therapy. METHODS: To achieve the aims, molecular docking was performed using several softwares such as LIGPLOT+, Python, and Protein-Ligand Interaction Profiler with corresponding tools. RESULTS: The IDE is a large zinc-metalloprotease that breakdown numerous pathophysiologically important extracellular substrates, comprising amyloid β-protein (Aβ) and insulin. Recent studies demonstrated that dysregulation of IDE leads to develop AD and T2D. Specifically, IDE regulates circulating insulin in a variety of organs via a degradation-dependent clearance mechanism. IDE is unique because it was subjected to allosteric activation and mediated via an oligomer structure. CONCLUSION: In this review, we summarised the factors that modulate insulin reformation by IDE and interaction of IDE and some recent reports on IDE inhibitors against AD and T2D. We also highlighted the latest signs of progress of the function of IDE and challenges in advancing IDE- targetted therapies against T2D and AD.
PURPOSE: This review aims to provide a precise perceptive of the insulin-degrading enzyme (IDE) and its relationship to type 2 diabetes (T2D), Alzheimer's disease (AD), obesity, and cardiovascular diseases. The purpose of the current study was to provide clear idea of treating prevalent diseases such as T2D, and AD by molecular pharmacological therapeutics rather than conventional medicinal therapy. METHODS: To achieve the aims, molecular docking was performed using several softwares such as LIGPLOT+, Python, and Protein-Ligand Interaction Profiler with corresponding tools. RESULTS: The IDE is a large zinc-metalloprotease that breakdown numerous pathophysiologically important extracellular substrates, comprising amyloid β-protein (Aβ) and insulin. Recent studies demonstrated that dysregulation of IDE leads to develop AD and T2D. Specifically, IDE regulates circulating insulin in a variety of organs via a degradation-dependent clearance mechanism. IDE is unique because it was subjected to allosteric activation and mediated via an oligomer structure. CONCLUSION: In this review, we summarised the factors that modulate insulin reformation by IDE and interaction of IDE and some recent reports on IDE inhibitors against AD and T2D. We also highlighted the latest signs of progress of the function of IDE and challenges in advancing IDE- targetted therapies against T2D and AD.
Authors: Wesley Farris; Malcolm A Leissring; Matthew L Hemming; Alice Y Chang; Dennis J Selkoe Journal: Biochemistry Date: 2005-05-03 Impact factor: 3.162