Department of Neurosurgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Department of Neurosurgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Int J Biol Macromol. 2021 Jul 1;182:91-97. doi: 10.1016/j.ijbiomac.2021.03.186. Epub 2021 Mar 30.
Protein misfolding and aggregation result in induction of a number of neurodegenerative diseases. In the present study, the anti-fibrillation activity of calycosin and its influence on the amyloid formation of α-synuclein (α-syn) and associated cytotoxicity on neuron-like cells (PC-12) as a model of Parkinson's disease were explored. Therefore, in combination with ThT and ANS fluorescence assay, CD, Congo red absorbance, TEM and cytotoxicity assays (MTT, ROS, SOD activity, CAT activity, GSH content, and caspase-3 activity assays), we showed that calycosin remarkably inhibits α-syn fibril formation through a concentration-dependent manner. The experimental analysis indicated that calycosin exert its antioxidant effects against α-syn amyloid-triggered neurotoxicity by modifying the aggregation pathway toward formation of nontoxic spices via recovering the activity of SOD/CAT and GSH content and reducing the ROS content and caspase-3 activity. This work may provide useful information about the mechanism of α-syn amyloid inhibition by calycosin and pave the way for developing some small molecules-based therapeutic platforms against Parkinson's disease.
蛋白质错误折叠和聚集导致了许多神经退行性疾病的发生。在本研究中，我们探讨了毛蕊异黄酮的抗纤维形成活性及其对α-突触核蛋白（α-syn）的淀粉样形成的影响，以及其对神经元样细胞（PC-12）的细胞毒性作用，PC-12 细胞被用作帕金森病的模型。因此，我们结合 ThT 和 ANS 荧光测定法、CD、刚果红吸收、TEM 和细胞毒性测定法（MTT、ROS、SOD 活性、CAT 活性、GSH 含量和 caspase-3 活性测定法），表明毛蕊异黄酮通过浓度依赖性方式显著抑制α-syn 纤维形成。实验分析表明，毛蕊异黄酮通过修饰聚集途径，使其形成无毒的构象，从而恢复 SOD/CAT 的活性和 GSH 含量，降低 ROS 含量和 caspase-3 活性，从而发挥其对α-syn 淀粉样纤维触发的神经毒性的抗氧化作用。这项工作可能为毛蕊异黄酮抑制α-syn 淀粉样形成的机制提供有用信息，并为开发针对帕金森病的基于小分子的治疗平台铺平道路。
