Recent evidence suggests that disease progression in Parkinson’s disease (PD) could occur by the spreading of α-synuclein (α-syn) aggregates between neurons. Here we studied the role of astrocytes in the intercellular transfer and fate of α-syn fibrils, using in vitro and ex vivo models. α-Syn fibrils can be transferred to neighboring cells; however, the transfer efficiency changes depending on the cell types. We found that α-syn is efficiently transferred from astrocytes to astrocytes and from neurons to astrocytes, but less efficiently from astrocytes to neurons. Interestingly, α-syn puncta are mainly found inside the lysosomal compartments of the recipient cells. However, differently from neurons, astrocytes are able to efficiently degrade fibrillar α-syn, suggesting an active role for these cells in clearing α-syn deposits. Astrocytes co-cultured with organotypic brain slices are able to take up α-syn fibrils from the slices. Altogether our data support a role for astrocytes in trapping and clearing α-syn pathological deposits in PD.

最近的证据表明，帕金森氏病（PD）的疾病进展可能是由于神经元之间的α-突触核蛋白（α-syn）聚集体扩散所致。在这里，我们使用体外和离体模型研究了星形胶质细胞在α-syn原纤维的细胞间转移和命运中的作用。α-Syn原纤维可以转移到相邻细胞中。但是，转移效率根据细胞类型而变化。我们发现α-syn有效地从星形胶质细胞转移到星形胶质细胞以及从神经元转移到星形胶质细胞，但是从星形胶质细胞转移到神经元的效率较低。有趣的是，α-syn点状斑点主要存在于受体细胞的溶酶体区室中。然而，与神经元不同，星形胶质细胞能够有效降解原纤维α-syn，提示这些细胞在清除α-syn沉积物中起积极作用。与器官型脑切片共培养的星形胶质细胞能够吸收切片中的α-syn原纤维。总之，我们的数据支持星形胶质细胞在PD中捕获和清除α-syn病理性沉积物中的作用。