Wang Bin, Li Nan, Wang Yuanxin, Tian Xin, Lin Junjie, Zhang Xin, Xu Haocheng, Sun Yu, Zhao Renqing
College of Physical Education, Yangzhou University, Yangzhou 225009, China.
Biology (Basel). 2025 Jul 29;14(8):955. doi: 10.3390/biology14080955.
Although exercise is known to exert anti-inflammatory effects in neurodegenerative diseases, its specific impact and underlying mechanisms in Parkinson's disease (PD) remain poorly understood. This study explores the effects of exercise on microglia-mediated neuroinflammation and apoptosis in a PD model, focusing on the role of irisin signaling in mediating these effects. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, we found that a 10-week treadmill exercise regimen significantly enhanced motor function, reduced dopaminergic neuron loss, attenuated neuronal apoptosis, and alleviated neuroinflammation. Exercise also shifted microglia from a pro-inflammatory to an anti-inflammatory phenotype. Notably, levels of irisin, phosphorylated AMP-activated protein kinase (p-AMPK), and sirtuin 1 (Sirt1), which were decreased in the PD brain, were significantly increased following exercise. These beneficial effects were abolished by blocking the irisin receptor with cyclic arginine-glycine-aspartic acid-tyrosine-lysine (cycloRGDyk). Our results indicate that exercise promotes neuroprotection in PD by modulating microglial activation and the AMPK/Sirt1 pathway through irisin signaling, offering new insights into exercise-based therapeutic approaches for PD.
尽管已知运动对神经退行性疾病具有抗炎作用，但其在帕金森病（PD）中的具体影响和潜在机制仍知之甚少。本研究探讨运动对PD模型中小胶质细胞介导的神经炎症和细胞凋亡的影响，重点关注鸢尾素信号在介导这些影响中的作用。使用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的PD小鼠模型，我们发现为期10周的跑步机运动方案显著增强了运动功能，减少了多巴胺能神经元损失，减轻了神经元凋亡，并缓解了神经炎症。运动还使小胶质细胞从促炎表型转变为抗炎表型。值得注意的是，在PD脑中降低的鸢尾素、磷酸化的AMP活化蛋白激酶（p-AMPK）和沉默调节蛋白1（Sirt1）水平在运动后显著升高。用环精氨酸-甘氨酸-天冬氨酸-酪氨酸-赖氨酸（cycloRGDyk）阻断鸢尾素受体可消除这些有益作用。我们的结果表明，运动通过鸢尾素信号调节小胶质细胞活化和AMPK/Sirt1途径，促进PD中的神经保护，为基于运动的PD治疗方法提供了新的见解。
