Department of Chemical and Food Engineering, Dhaka University of Engineering & Technology, Gazipur, 1707, Bangladesh.
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.
Pharm Res. 2022 Apr;39(4):611-629. doi: 10.1007/s11095-022-03237-7. Epub 2022 Apr 4.
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.
To achieve the aims, molecular docking was performed using several softwares such as LIGPLOT+, Python, and Protein-Ligand Interaction Profiler with corresponding tools.
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.
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.
本综述旨在提供胰岛素降解酶（IDE）的精确认识及其与 2 型糖尿病（T2D）、阿尔茨海默病（AD）、肥胖症和心血管疾病的关系。本研究的目的是通过分子药理学治疗而非传统药物治疗，为治疗 T2D 和 AD 等常见疾病提供清晰的思路。
为了实现目标，使用 LIGPLOT+、Python 和 Protein-Ligand Interaction Profiler 等软件及其相应工具进行了分子对接。
IDE 是一种大型锌金属蛋白酶，可分解许多生理病理上重要的细胞外底物，包括淀粉样β蛋白（Aβ）和胰岛素。最近的研究表明，IDE 的失调会导致 AD 和 T2D 的发生。具体而言，IDE 通过降解依赖性清除机制调节多种器官中的循环胰岛素。IDE 是独特的，因为它受到变构激活和寡聚体结构的介导。
在本综述中，我们总结了调节 IDE 胰岛素再形成的因素以及 IDE 与一些针对 AD 和 T2D 的 IDE 抑制剂的相互作用。我们还强调了 IDE 功能的最新研究进展以及在推进针对 T2D 和 AD 的 IDE 靶向治疗方面的挑战。
