Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Tottori, 680-8552, Japan.
Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Tottori, 680-8552, Japan.
Appl Biochem Biotechnol. 2023 Jul;195(7):4134-4147. doi: 10.1007/s12010-023-04362-8. Epub 2023 Jan 19.
Intracellular aggregation of α-synuclein is a major pathological feature of Parkinson's disease. In this study, we show that the polyphenols delphinidin and rosmarinic acid suppress intracellular aggregation of α-synuclein in a mouse neuron cell model when added under oxidative stress conditions. To enhance the detection threshold of this preventive effect of the two polyphenols, we generated a new strain of "aggregation prone model cells" that tended to show prominent α-synuclein aggregation even under normal conditions. Using this new highly sensitive cell line, we demonstrate that addition of delphinidin to model cell cultures effectively suppresses the formation of intracellular α-synuclein aggregates. Flow cytometric analysis shows that adding delphinidin decreases the fraction of "dying cells," cells that were alive but in a damaged state. Our findings suggest the possibility of using polyphenols to prevent and treat the symptoms correlated with the onset of Parkinson's disease. Additionally, our aggregation-prone cell model may be used in future studies to probe numerous neurodegenerative diseases with high sensitivity.
α-突触核蛋白的细胞内聚集是帕金森病的主要病理特征。在这项研究中，我们表明，在氧化应激条件下添加时，多酚飞燕草素和迷迭香酸可抑制小鼠神经元细胞模型中α-突触核蛋白的细胞内聚集。为了增强这两种多酚的预防作用的检测阈值，我们生成了一种新的“易于聚集的模型细胞”菌株，即使在正常条件下也倾向于表现出明显的α-突触核蛋白聚集。使用这种新的高灵敏度细胞系，我们证明向模型细胞培养物中添加飞燕草素可有效抑制细胞内α-突触核蛋白聚集体的形成。流式细胞术分析表明，添加飞燕草素可降低“死亡细胞”（即处于存活但受损状态的细胞）的比例。我们的研究结果表明，使用多酚来预防和治疗与帕金森病发病相关的症状是可能的。此外，我们的易于聚集的细胞模型可能在未来的研究中用于高灵敏度地探测许多神经退行性疾病。
