Zhang Jiping, Fu Zhiyi, Wen Feng, Lyu Peilin, Huang Shengtao, Cai Xiaowen, Zhang Zhinan, Zhang Ying, Fan Chun, Man Weitao, Sun Xiaomin, Huang Yong
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People's Republic of China.
Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
J Neurophysiol. 2025 Feb 1;133(2):490-501. doi: 10.1152/jn.00497.2024. Epub 2025 Jan 2.
Parkinson's disease (PD) is a prevalent and challenging neurodegenerative disorder, and may involve impaired autophagy. Nuclear factor erythroid-2-related factor 2 (Nrf2) is crucial for regulating autophagy-related genes and maintaining cellular homeostasis. Electroacupuncture (EA), a complementary and alternative therapy for PD, has gained widespread clinical application. In this study, we investigate whether EA at Baihui (GV20) and Taichong (LR3) acupoints modulates autophagy through the Nrf2 pathway, providing neuroprotection in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. Using wild-type and Nrf2 knockout (KO) mice, we examined EA's effects on dopaminergic neuron survival, α-synuclein expression, motor function and the underlying mechanisms. Results showed that EA treatment significantly reduced dopaminergic neuron loss and α-synuclein expression, and improved motor deficits while restoring autophagy, as evidenced by increased autophagy markers (Atg7, LC3II) and decreased p62 levels. Transmission electron microscopy confirmed a rise in autophagosomes and lysosomes in the MPTP + EA group. EA also enhanced nuclear Nrf2 expression and activated Nrf2 signaling. Importantly, Nrf2 KO mice did not exhibit neuroprotection or increased autophagy-related proteins following EA treatment. In conclusion, our research demonstrated that EA ameliorated defective autophagy and activated the Nrf2 signaling pathway, which collectively contribute to its neuroprotective effects against MPTP-induced neurotoxicity. In this study, we explored the potential mechanism of electroacupuncture (EA) therapy at the GV20 and LR3 acupoints of Parkinson's disease (PD). We demonstrated EA therapy's neuroprotective effect on PD, through ameliorating defective autophagy and activating the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway whereas the regulation of EA on autophagy was absent in Nrf2 knockout (KO) mice. Our study not only provides new insights into the therapeutic mechanisms of EA but also suggests a promising strategy for PD treatment.
帕金森病（PD）是一种常见且具有挑战性的神经退行性疾病，可能涉及自噬受损。核因子红细胞2相关因子2（Nrf2）对于调节自噬相关基因和维持细胞稳态至关重要。电针（EA）作为PD的一种补充和替代疗法，已在临床广泛应用。在本研究中，我们探究针刺百会（GV20）和太冲（LR3）穴位是否通过Nrf2通路调节自噬，从而为1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的PD小鼠提供神经保护作用。我们使用野生型和Nrf2基因敲除（KO）小鼠，研究电针对多巴胺能神经元存活、α-突触核蛋白表达、运动功能及潜在机制的影响。结果显示，电针治疗显著减少了多巴胺能神经元丢失和α-突触核蛋白表达，改善了运动功能障碍，同时恢复了自噬，自噬标志物（Atg7、LC3II）增加及p62水平降低证明了这一点。透射电子显微镜证实MPTP + EA组自噬体和溶酶体增加。电针还增强了核Nrf2表达并激活了Nrf2信号通路。重要的是，Nrf2基因敲除小鼠在电针治疗后未表现出神经保护作用或自噬相关蛋白增加。总之，我们的研究表明，电针改善了自噬缺陷并激活了Nrf2信号通路，共同促成了其对MPTP诱导的神经毒性的神经保护作用。在本研究中，我们探索了帕金森病（PD）电针（EA）治疗在GV20和LR3穴位的潜在机制。我们证明了电针治疗对PD具有神经保护作用，通过改善自噬缺陷和激活核因子红细胞2相关因子2（Nrf2）信号通路，而在Nrf2基因敲除（KO）小鼠中电针缺乏对自噬的调节作用。我们的研究不仅为电针的治疗机制提供了新见解，也为PD治疗提出了一个有前景的策略。
