Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra, Saudi Arabia.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
J Alzheimers Dis. 2024;99(1):333-343. doi: 10.3233/JAD-240072.
Neurodegeneration is a term describing an irreversible process of neuronal damage. In recent decades, research efforts have been directed towards deepening our knowledge of numerous neurodegenerative disorders, with a particular focus on conditions such as Alzheimer's disease (AD). Human transferrin (htf) is a key player in maintaining iron homeostasis within brain cells. Any disturbance in this equilibrium gives rise to the emergence of neurodegenerative diseases and associated pathologies, particularly AD. Limonene, a natural compound found in citrus fruits and various plants, has shown potential neuroprotective properties.
In this study, our goal was to unravel the binding of limonene with htf, with the intention of comprehending the interaction mechanism of limonene with htf.
Binding was scrutinized using fluorescence quenching and UV-Vis spectroscopic analyses. The binding mechanism of limonene was further investigated at the atomic level through molecular docking and extensive 200 ns molecular dynamic simulation (MD) studies.
Molecular docking uncovered that limonene interacted extensively with the deep cavity located within the htf binding pocket. MD results indicated that binding of limonene to htf did not induce substantial structural alterations, ultimately forming stable complex. The findings from fluorescence binding indicated a pronounced interaction between limonene and htf, limonene binds to htf with a binding constant (K) of 0.1×105 M-1. UV spectroscopy also advocated stable htf-limonene complex formation.
The study deciphered the binding mechanism of limonene with htf, providing a platform to use limonene in AD therapeutics in context of iron homeostasis.
神经退行性变是描述神经元损伤不可逆转过程的一个术语。近几十年来，研究工作的重点是加深对许多神经退行性疾病的认识，特别是阿尔茨海默病（AD）。人转铁蛋白（htf）是维持脑细胞内铁平衡的关键因素。这种平衡的任何干扰都会导致神经退行性疾病和相关病理的出现，特别是 AD。柠檬烯是一种在柑橘类水果和各种植物中发现的天然化合物，具有潜在的神经保护特性。
在这项研究中，我们的目标是揭示柠檬烯与 htf 的结合，旨在理解柠檬烯与 htf 的相互作用机制。
使用荧光猝灭和紫外-可见光谱分析来研究结合。通过分子对接和广泛的 200ns 分子动力学模拟（MD）研究进一步研究了柠檬烯与 htf 的结合机制。
分子对接发现柠檬烯与位于 htf 结合口袋深处的腔广泛相互作用。MD 结果表明，柠檬烯与 htf 的结合不会引起结构的显著变化，最终形成稳定的复合物。荧光结合的结果表明柠檬烯与 htf 之间存在显著的相互作用，柠檬烯与 htf 的结合常数（K）为 0.1×105M-1。紫外光谱也支持 htf-柠檬烯复合物的形成。
该研究阐明了柠檬烯与 htf 的结合机制，为在 AD 治疗中利用柠檬烯维持铁平衡提供了一个平台。
