Graduate Institute of Biomedical Sciences, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
Department of Anesthesiology, China Medical University Hospital, Taichung 40447, Taiwan.
Am J Chin Med. 2020;48(7):1651-1669. doi: 10.1142/S0192415X20500822. Epub 2020 Nov 13.
Autophagic defects are a hallmark of neurodegenerative disorders, such as Parkinson's disorder (PD). Enhancing autophagy to remove impaired mitochondria and toxic protein aggregation is an essential component of PD treatment. In particular, activation of autophagy confers neuroprotection in cellular and preclinical models of neurodegenerative diseases. In this study, we investigated the therapeutic mechanisms of electroacupuncture (EA) treatment in mice with established PD and evaluated the relationship between EA, autophagy, and different neurons in the mouse brain. We report that EA improves PD motor symptoms in mice and enhances (1) autophagy initiation (increased Beclin 1), (2) autophagosome biogenesis (increased Atg5, Atg7, Atg9A, Atg12, Atg16L, Atg3, and LC3-II), (3) autophagy flux/substrate degradation (decreased p62), and (4) mitophagy (increased PINK1 and DJ-1) in neurons of the substantia nigra, striatum, hippocampus, and cortex (affected brain areas of PD, Huntington disease, and Alzheimer's disease). EA enhances autophagy initiation, autophagosome biogenesis, mitophagy, and autophagy flux/substrate degradation in certain brain areas. Our findings are the first to show that EA regulates neuronal autophagy and suggest that this convenient, inexpensive treatment has exciting therapeutic potential in neurodegenerative disorders.
自噬缺陷是神经退行性疾病的标志,如帕金森病(PD)。增强自噬以清除受损的线粒体和毒性蛋白聚集体是 PD 治疗的重要组成部分。特别是,自噬的激活在神经退行性疾病的细胞和临床前模型中赋予了神经保护作用。在这项研究中,我们研究了电针(EA)治疗在已建立的 PD 小鼠中的治疗机制,并评估了 EA、自噬和小鼠大脑中不同神经元之间的关系。我们报告说,EA 改善了 PD 小鼠的运动症状,并增强了(1)自噬起始(增加 Beclin 1),(2)自噬体生物发生(增加 Atg5、Atg7、Atg9A、Atg12、Atg16L、Atg3 和 LC3-II),(3)自噬流/底物降解(减少 p62),和(4)线粒体自噬(增加 PINK1 和 DJ-1)在黑质、纹状体、海马体和皮质的神经元中(PD、亨廷顿病和阿尔茨海默病的受影响大脑区域)。EA 增强了某些大脑区域的自噬起始、自噬体生物发生、线粒体自噬和自噬流/底物降解。我们的发现首次表明,EA 调节神经元自噬,并表明这种方便、廉价的治疗方法在神经退行性疾病中有令人兴奋的治疗潜力。