Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, Paris, France.
Paris-Saclay Institute of Neuroscience, CNRS, Gif-sur-Yvette, France.
Acta Neuropathol. 2017 Nov;134(5):789-808. doi: 10.1007/s00401-017-1746-2. Epub 2017 Jul 19.
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，帕金森病（PD）中的疾病进展可能是通过α-突触核蛋白（α-syn）聚集体在神经元之间的扩散而发生的。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 原纤维可以转移到邻近的细胞；然而，转移效率取决于细胞类型。我们发现α-syn 可以有效地从星形胶质细胞转移到星形胶质细胞，从神经元转移到星形胶质细胞，但从星形胶质细胞转移到神经元的效率较低。有趣的是，α-syn 斑点主要存在于受体细胞的溶酶体隔室中。然而，与神经元不同的是，星形胶质细胞能够有效地降解纤维状α-syn，这表明这些细胞在清除α-syn 沉积方面具有积极作用。与器官型脑切片共培养的星形胶质细胞能够从切片中摄取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 病理性沉积的作用。
