Dalle Molle Institute for Artificial Intelligence (IDSIA), University of Italian Switzerland (USI), University of Applied Science and Art of Southern Switzerland (SUPSI), CH-6928 Manno, Switzerland.
PolitoBIOMed Lab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, IT-10128 Torino, Italy.
Int J Mol Sci. 2020 Mar 16;21(6):2017. doi: 10.3390/ijms21062017.
The pursuit for effective strategies inhibiting the amyloidogenic process in neurodegenerative disorders, such as Alzheimer's disease (AD), remains one of the main unsolved issues, and only a few drugs have demonstrated to delay the degeneration of the cognitive system. Moreover, most therapies induce severe side effects and are not effective at all stages of the illness. The need to find novel and reliable drugs appears therefore of primary importance. In this context, natural compounds have shown interesting beneficial effects on the onset and progression of neurodegenerative diseases, exhibiting a great inhibitory activity on the formation of amyloid aggregates and proving to be effective in many preclinical and clinical studies. However, their inhibitory mechanism is still unclear. In this work, ensemble docking and molecular dynamics simulations on S-shaped Aβ fibrils have been carried out to evaluate the influence of several natural compounds on amyloid conformational behaviour. A deep understanding of the interaction mechanisms between natural compounds and Aβ aggregates may play a key role to pave the way for design, discovery and optimization strategies toward an efficient destabilization of toxic amyloid assemblies.
在神经退行性疾病（如阿尔茨海默病，AD）中，寻找有效的抑制淀粉样蛋白形成的策略仍然是一个未解决的主要问题，只有少数药物被证明可以延缓认知系统的退化。此外，大多数治疗方法会引起严重的副作用，并且在疾病的各个阶段都没有效果。因此，寻找新型、可靠的药物显得尤为重要。在这种情况下，天然化合物在神经退行性疾病的发生和发展方面显示出了有趣的有益作用，对淀粉样蛋白聚集的形成具有很强的抑制活性，并在许多临床前和临床试验中被证明是有效的。然而，其抑制机制尚不清楚。在这项工作中，对 S 形 Aβ 纤维进行了集合对接和分子动力学模拟，以评估几种天然化合物对淀粉样蛋白构象行为的影响。深入了解天然化合物与 Aβ 聚集物之间的相互作用机制，可能对设计、发现和优化策略以有效破坏有毒淀粉样蛋白组装物起到关键作用。
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