Role of exosomes in the pathogenesis of inflammation in Parkinson's disease.
Role of exosomes in the pathogenesis of inflammation in Parkinson's disease.
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DOI：
10.4103/1673-5374.335143
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发表时间：
2022-09
影响因子：
6.1
通讯作者：
Yang XL
中科院分区：
文献类型：
--
作者：
Li KL;Huang HY;Ren H;Yang XL
炎症反应，包括神经胶质细胞激活和外周免疫细胞浸润，参与帕金森病（PD）的发病机制。这些炎症反应似乎与细胞外囊泡（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。本文讨论了外泌体在pd相关炎症中的多种作用，并得出结论：外泌体可以将有毒的α-突触核蛋白低聚物转运到未成熟神经元并进入细胞外环境，诱导正常神经元α-突触核蛋白低聚。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。神经胶质细胞衍生的外泌体参与神经胶质细胞和神经元之间的通讯，引发抗应激和抗炎反应，以及轴突生长。线粒体囊泡和外泌体的产生和释放为线粒体功能障碍与帕金森病相关的全身性炎症建立了新的联系机制。鉴于外泌体作为神经炎症和神经发病机制中神经元-胶质细胞通讯介质的相关性，目前正在开发利用这些类型的细胞外囊泡作为药物载体的新的靶向治疗策略。外泌体介导的炎症可能是PD患者干预的一个有希望的目标。
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.
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