Waseem Rashid, Shamsi Anas, Mohammad Taj, Alhumaydhi Fahad A, Kazim Syed Naqui, Hassan Md Imtaiyaz, Ahmad Faizan, Islam Asimul
Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.
Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 52571, Saudi Arabia.
ACS Omega. 2021 Mar 8;6(11):7910-7921. doi: 10.1021/acsomega.1c00517. eCollection 2021 Mar 23.
This study was aimed to study the interaction between purified irisin and rivastigmine tartrate (RT), a cholinesterase inhibitor used in Alzheimer's therapy. Irisin mainly promotes brown fat-like features in white adipose tissues; however, it has some important role in the nervous system also, i.e., capable of opposing synapse and memory failure in Alzheimer's disease (AD). The recombinant protein was purified by Ni-NTA chromatography and characterized using spectroscopic and techniques. Further, the mechanism of interaction between irisin and RT was investigated using various biophysical techniques. Fluorescence quenching studies suggested that there exists a moderate binding between irisin and RT with a binding constant () of 10 M and the irisin-RT complex is guided by a combination of both static and dynamic modes of quenching. Thermodynamic parameters suggested the reaction to be driven by hydrogen bonding, making it specific. FTIR and CD spectroscopy suggested no secondary structural alterations in irisin in the presence of RT. Molecular docking investigation provided an insight into the important residues that play a key role in irisin-RT interactions. This study delineates an important finding in AD therapy and can provide a platform further to explore the potential of irisin in AD treatment.
本研究旨在探讨纯化的鸢尾素与用于阿尔茨海默病治疗的胆碱酯酶抑制剂酒石酸卡巴拉汀（RT）之间的相互作用。鸢尾素主要促进白色脂肪组织呈现棕色脂肪样特征；然而，它在神经系统中也具有一些重要作用，即能够对抗阿尔茨海默病（AD）中的突触和记忆衰退。重组蛋白通过镍-氮三乙酸（Ni-NTA）色谱法纯化，并使用光谱学和其他技术进行表征。此外，利用各种生物物理技术研究了鸢尾素与RT之间的相互作用机制。荧光猝灭研究表明，鸢尾素与RT之间存在适度结合，结合常数（）为10 M，鸢尾素-RT复合物由静态和动态猝灭模式共同作用形成。热力学参数表明该反应由氢键驱动，具有特异性。傅里叶变换红外光谱（FTIR）和圆二色光谱（CD）表明，在RT存在的情况下，鸢尾素的二级结构没有改变。分子对接研究揭示了在鸢尾素与RT相互作用中起关键作用的重要残基。本研究阐述了AD治疗中的一项重要发现，并可为进一步探索鸢尾素在AD治疗中的潜力提供一个平台。
