Zhao Liang, Jiang Weiye, Zhu Zehui, Pan Fei, Xing Xin, Zhou Feng, Zhao Lei
Key Laboratory of Geriatric Nutrition and Health, Beijing Technology and Business University, Ministry of Education, Beijing 100048, China.
Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing 100048, China.
Foods. 2024 Dec 23;13(24):4170. doi: 10.3390/foods13244170.
Alzheimer's disease (AD) is a neurodegenerative disorder marked by the progressive accumulation of amyloid-β (Aβ) plaques and tau protein tangles in the brain. These pathological aggregates interfere with neuronal function, leading to the disruption of cognitive processes, particularly memory. The deposition of Aβ forms senile plaques, while tau protein, in its hyperphosphorylated state, forms neurofibrillary tangles, both of which contribute to the underlying neurodegeneration observed in AD. Rosmarinic acid (RosA), a natural compound found in plants such as , is known for its antioxidant, anti-inflammatory, and antimicrobial properties. Due to its ability to cross the blood-brain barrier, RosA holds promise as a nutritional supplement that may support brain health. In this study, molecular dynamics (MD) simulations were used to investigate the impact of RosA on the structural stability of Aβ peptides. The results indicated that the addition of RosA increased the instability of Aβ, as evidenced by an increase in the Root Mean Square Deviation (RMSD), a decrease in the Radius of Gyration (Rg), and an expansion of the Solvent Accessible Surface Area (SASA). This destabilization is primarily attributed to the disruption of native hydrogen bonds and hydrophobic interactions in the presence of two RosA molecules. The free energy landscape (FEL) analysis and MM-PBSA (Poisson-Boltzmann Surface Area Mechanics) results further support the notion that RosA can effectively bind to the hydrophobic pocket of the protein, highlighting its potential as a nutritional component that may contribute to maintaining brain health and function.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是大脑中β-淀粉样蛋白（Aβ）斑块和tau蛋白缠结的逐渐积累。这些病理聚集体干扰神经元功能，导致认知过程特别是记忆的破坏。Aβ的沉积形成老年斑，而处于高磷酸化状态的tau蛋白形成神经原纤维缠结，这两者都导致了AD中观察到的潜在神经退行性变。迷迭香酸（RosA）是一种存在于迷迭香等植物中的天然化合物，以其抗氧化、抗炎和抗菌特性而闻名。由于其能够穿过血脑屏障，RosA有望作为一种可能支持大脑健康的营养补充剂。在这项研究中，使用分子动力学（MD）模拟来研究RosA对Aβ肽结构稳定性的影响。结果表明，添加RosA会增加Aβ的不稳定性，均方根偏差（RMSD）增加、回转半径（Rg）减小以及溶剂可及表面积（SASA）扩大都证明了这一点。这种不稳定主要归因于在两个RosA分子存在下天然氢键和疏水相互作用的破坏。自由能景观（FEL）分析和MM-PBSA（泊松-玻尔兹曼表面积力学）结果进一步支持了RosA可以有效结合到蛋白质疏水口袋的观点，突出了其作为一种可能有助于维持大脑健康和功能的营养成分的潜力。
