Biomedical Industry Ph.D. Program, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.
Bened Biomedical Co., Ltd., Taipei 10448, Taiwan.
Int J Mol Sci. 2023 Apr 5;24(7):6794. doi: 10.3390/ijms24076794.
Parkinson's disease (PD) is a neurodegenerative disease characterized by motor deficits and marked neuroinflammation in various brain regions. The pathophysiology of PD is complex and mounting evidence has suggested an association with the dysregulation of microRNAs (miRNAs) and gut dysbiosis. Using a rotenone-induced PD mouse model, we observed that administration of PS128 (PS128) significantly improved motor deficits in PD-like mice, accompanied by an increased level of dopamine, reduced dopaminergic neuron loss, reduced microglial activation, reduced levels of inflammatory factors, and enhanced expression of neurotrophic factor in the brain. Notably, the inflammation-related expression of miR-155-5p was significantly upregulated in the proximal colon, midbrain, and striatum of PD-like mice. PS128 reduced the level of miR-155-5p, whereas it increased the expression of suppressor of cytokine signaling 1 (SOCS1), a direct target of miR-155-5p and a critical inhibitor of the inflammatory response in the brain. Alteration of the fecal microbiota in PD-like mice was partially restored by PS128 administration. Among them, , _6, , and were statistically correlated with the improvement of rotenone-induced motor deficits and the expression of miR-155-5p and SOCS1. Our findings suggested that PS128 ameliorates motor deficits and exerts neuroprotective effects by regulating the gut microbiota and miR-155-5p/SOCS1 pathway in rotenone-induced PD-like mice.
帕金森病（PD）是一种神经退行性疾病，其特征是在大脑的不同区域存在运动缺陷和明显的神经炎症。PD 的病理生理学非常复杂，越来越多的证据表明其与 microRNAs（miRNAs）的失调和肠道菌群失调有关。使用鱼藤酮诱导的 PD 小鼠模型，我们观察到 PS128 治疗显著改善了 PD 样小鼠的运动缺陷，伴随着多巴胺水平的增加、多巴胺能神经元损失的减少、小胶质细胞激活的减少、炎症因子水平的降低以及神经营养因子在大脑中的表达增强。值得注意的是，PD 样小鼠近端结肠、中脑和纹状体中炎症相关的 miR-155-5p 表达显著上调。PS128 降低了 miR-155-5p 的水平，而增加了其直接靶标细胞因子信号转导抑制因子 1（SOCS1）的表达，SOCS1 是大脑中炎症反应的关键抑制剂。PS128 给药部分恢复了 PD 样小鼠的粪便微生物群改变。其中， 、 、 与鱼藤酮诱导的运动缺陷的改善和 miR-155-5p 和 SOCS1 的表达呈统计学相关。我们的研究结果表明，PS128 通过调节肠道微生物群和 miR-155-5p/SOCS1 通路，改善了鱼藤酮诱导的 PD 样小鼠的运动缺陷并发挥了神经保护作用。
