中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (9): 1898-1906.doi: 10.4103/1673-5374.335143

• 综述:退行性病与再生 • 上一篇    下一篇

外泌体在帕金森病炎症反应中的作用

  

  • 出版日期:2022-09-15 发布日期:2022-03-05

Role of exosomes in the pathogenesis of inflammation in Parkinson’s disease

Ke-Lu Li1, Hong-Yan Huang2, Hui Ren1, Xing-Long Yang1, *   

  1. 1Department of Geriatric Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China; 2Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
  • Online:2022-09-15 Published:2022-03-05
  • Contact: Xing-Long Yang, PhD, yxldoc11@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81960242 (to XLY); Yunnan Applied Basic Research Project of Yunnan Province of China, Nos. 2019FE001-048 (to XLY), 202001AT070001 (to XLY), “One Hundred Young and Middle-aged Academic and Technical Backbone” Training Program of Kunming Medical University, No. 60118260105 (to XLY); Miaozi Project in Science and Technology Innovation Program of Sichuan Province, No. 2020JDRC0057 (to HYH).

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摘要：

炎症反应包括胶质细胞活化和外周免疫细胞浸润，它参与了帕金森病的发病机制。这些炎症反应似乎与细胞外小泡(如外泌体)的释放密切相关。然而，不同形式的胶质细胞活化、突触核蛋白失调、线粒体功能障碍和外泌体之间的关系是复杂的。文章讨论了以往诸多文献对外泌体于帕金森病炎症反应的多重关系发现：(1)外泌体可将毒性α突触核蛋白寡聚体转运至未成熟神经元并进入细胞外环境，诱导正常神经元α突触核蛋白寡聚，而错误折叠的α突触核蛋白导致小胶质细胞和星形胶质细胞激活并分泌外泌体；(2)胶质细胞衍生的外泌体参与胶质细胞和神经元之间的细胞通讯过程，并可促进抗应激、抗炎反应和轴突生长；(3)线粒体囊泡和外泌体的产生释放建立了一种新的机制，这种机制将线粒体功能障碍与帕金森病相关的全身炎症联系起来，可进一步解释帕金森病的发病原因；(4)鉴于作为神经胶质细胞通讯递质的外泌体与神经炎症和神经病变中的相关性，目前研究者们着眼于细胞外泌体作为药物载体的新靶向治疗策略，希望为对帕金森病找到有希望的干预靶点。

https://orcid.org/0000-0001-5801-5211 (Xing-Long Yang)

关键词: 星形胶质细胞, 外泌体, 炎症, 线粒体, 小胶质细胞, 神经胶质细胞, 神经退行性变, 神经元-胶质细胞通讯, 帕金森病, 突触核蛋白

Abstract: Inflammatory responses, including glial cell activation and peripheral immune cell infiltration, are involved in the pathogenesis of Parkinson’s disease (PD). These inflammatory responses appear to be closely related to the release of extracellular vesicles, such as exosomes. However, the relationships among different forms of glial cell activation, synuclein dysregulation, mitochondrial dysfunction, and exosomes are complicated. This review discusses the multiple roles played by exosomes in PD-associated inflammation and concludes that exosomes can transport toxic α-synuclein oligomers to immature neurons and into the extracellular environment, inducing the oligomerization of α-synuclein in normal neurons. Misfolded α-synuclein causes microglia and astrocytes to activate and secrete exosomes. Glial cell-derived exosomes participate in communications between glial cells and neurons, triggering anti-stress and anti-inflammatory responses, in addition to axon growth. The production and release of mitochondrial vesicles and exosomes establish a new mechanism for linking mitochondrial dysfunction to systemic inflammation associated with PD. Given the relevance of exosomes as mediators of neuron-glia communication in neuroinflammation and neuropathogenesis, new targeted treatment strategies are currently being developed that use these types of extracellular vesicles as drug carriers. Exosome-mediated inflammation may be a promising target for intervention in PD patients.

Key words: astrocytes, exosomes, inflammation, microglia, mitochondria, neurodegeneration, neuroglia, neuron-glia communication, Parkinson’s disease, synucleins