Alrouji Mohammed, Alshammari Mohammed S, Majrashi Taghreed A, Zuberi Azna, Shahwan Moyad, Atiya Akhtar, Shamsi Anas
Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra, Saudi Arabia.
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Shaqra, Saudi Arabia.
Front Pharmacol. 2025 Mar 19;16:1540736. doi: 10.3389/fphar.2025.1540736. eCollection 2025.
Neurodegeneration is a progressive loss of neurons that leads to affected cognitive and motor functions and is characterized by neurodegenerative disorders (NDs). Human transferrin (Htf) is a blood plasma glycoprotein that binds to iron and regulates the free iron in biological fluids. Free iron is a potent neurotoxin associated with the generation of Reactive oxygen species (ROS) and is ultimately linked to oxidative stress and neuronal damage. Thus, targeting iron homeostasis is an attractive strategy for the management of NDs, viz. Alzheimer's disease (AD). Tryptamine (Trp) is a naturally occurring monoamine, that has demonstrated promising roles in AD therapeutics. The present study aims to delineate the binding mechanism of Trp with Htf employing computational and spectroscopic approaches. Molecular docking ascertained the vital residues governing the Htf-Trp complex formation. Further, Molecular dynamic (MD) studies ascertained the structural dynamics and stability of the complex, implying that the binding of Trp causes minimal structural alterations in Htf, suggestive of the stability of the complex. The results from fluorescence spectroscopy demonstrated the binding of Trp with Htf with a binding constant () of 0.48 × 10 M, validating the observations. This study provides a platform to understand the binding mechanism that may lead to novel therapeutic approaches targeting AD.
神经退行性变是神经元的渐进性丧失，导致认知和运动功能受到影响，其特征为神经退行性疾病（NDs）。人转铁蛋白（Htf）是一种血浆糖蛋白，可与铁结合并调节生物体液中的游离铁。游离铁是一种强效神经毒素，与活性氧（ROS）的产生有关，最终与氧化应激和神经元损伤相关。因此，针对铁稳态进行调控是治疗NDs（如阿尔茨海默病（AD））的一种有吸引力的策略。色胺（Trp）是一种天然存在的单胺，已在AD治疗中显示出有前景的作用。本研究旨在采用计算和光谱方法来阐明Trp与Htf的结合机制。分子对接确定了控制Htf-Trp复合物形成的关键残基。此外，分子动力学（MD）研究确定了该复合物的结构动力学和稳定性，这意味着Trp的结合在Htf中引起的结构变化最小，表明该复合物具有稳定性。荧光光谱结果表明Trp与Htf结合，结合常数（）为0.48×10 M，证实了这些观察结果。本研究提供了一个平台，以了解可能导致针对AD的新型治疗方法的结合机制。
