α-Synuclein (α-Syn) aggregates, the major toxic component of Lewy bodies, are proteinaceous fibrillar cytoplasmic inclusions observed in α-synucleinopathies, such as Parkinson’s disease (PD), multiple system atrophy, and dementia with Lewy bodies. Overexpression of α-syn induce neuronal loss and α-syn aggregation in PD animals. Recent studies show that α-syn is released by exocytosis and can be transmitted between brain areas through cell-to-cell propagation. Moreover, aggregates of extracellular α-syn can induce neuroinflammation-mediated neurotoxic signaling through microglial activation and release of pro-inflammatory factors. Thus, modulation of α-syn might be a potential therapeutic strategy for modifying disease progression of α-synucleinopathies. Our previous studies have revealed that MSCs have potent neuroprotective effects in PD animal through modulation of neuroinflammation, inhibition of cell death, and promotion of neurogenesis. Here, we provide further evidence that MSCs have the potential to modulate α-syn-related microenvironments via enhancement of autophagy, proteolysis of α-syn aggregates, inhibition of cell-to-cell transmission of α-syn, stabilization of axonal transport, and phagocytic clearance of α-syn by microglial M2 polarization. With advantages in clinical applications, these data suggests that the use of MSCs as pharmacological modulators of α-syn propagation would be an effective therapeutic approach in PD.

α-突触核蛋白（α-Syn）聚集体是路易氏体的主要毒性成分，是在α-突触核蛋白病中观察到的蛋白性纤维状细胞质内含物，例如帕金森氏病（PD），多系统萎缩和路易氏体痴呆。α-syn的过表达在PD动物中引起神经元丢失和α-syn聚集。最近的研究表明，α-syn通过胞吐作用释放，并且可以通过细胞间传播在大脑区域之间传播。此外，细胞外α-syn的聚集体可通过小胶质细胞活化和促炎因子的释放诱导神经炎症介导的神经毒性信号传导。因此，调节α-syn可能是修饰α-突触核病的疾病进展的潜在治疗策略。我们以前的研究表明，MSC通过调节神经炎症，抑制细胞死亡和促进神经发生，对PD动物具有有效的神经保护作用。在这里，我们提供了进一步的证据，表明MSC具有通过增强自噬，α-syn聚集蛋白水解，抑制α-syn的细胞间传递，轴突运输的稳定和调节α-syn相关的微环境的潜力。小胶质细胞M2极化吞噬α-syn。凭借在临床应用中的优势，这些数据表明，使用MSC作为α-syn传播的药理调节剂将是PD中一种有效的治疗方法。我们提供了进一步的证据，表明间充质干细胞具有通过增强自噬，α-syn聚集蛋白水解，抑制α-syn的细胞间传递，轴突运输的稳定和吞噬作用来调节与α-syn相关的微环境的潜力。小胶质细胞M2极化作用产生的α-syn。凭借在临床应用中的优势，这些数据表明，使用MSC作为α-syn传播的药理调节剂将是PD中一种有效的治疗方法。我们提供了进一步的证据，表明间充质干细胞具有通过增强自噬，α-syn聚集蛋白水解，抑制α-syn的细胞间传递，轴突运输的稳定和吞噬作用来调节与α-syn相关的微环境的潜力。小胶质细胞M2极化作用产生的α-syn。凭借在临床应用中的优势，这些数据表明，使用MSC作为α-syn传播的药理调节剂将是PD中一种有效的治疗方法。