The presence of Lewy bodies, mainly consisting of aggregated α-synuclein, is a pathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The α-synuclein inclusions are predominantly found in neurons, but also appear frequently in astrocytes. However, the pathological significance of α-synuclein inclusions in astrocytes and the capacity of glial cells to clear toxic α-synuclein species remain unknown. In the present study we investigated uptake, degradation and toxic effects of oligomeric α-synuclein in a co-culture system of primary neurons, astrocytes and oligodendrocytes. Alpha-synuclein oligomers were found to co-localize with the glial cells and the astrocytes were found to internalize particularly large amounts of the protein. Following ingestion, the astrocytes started to degrade the oligomers via the lysosomal pathway but, due to incomplete digestion, large intracellular deposits remained. Moreover, the astrocytes displayed mitochondrial abnormalities. Taken together, our data indicate that astrocytes play an important role in the clearance of toxic α-synuclein species from the extracellular space. However, when their degrading capacity is overburdened, α-synuclein deposits can persist and result in detrimental cellular processes.

中文翻译：

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星形胶质细胞中大量摄取α-突触核蛋白寡聚体导致持续的细胞内沉积和线粒体损伤。

路易小体的存在主要由聚集的α-突触核蛋白组成，是帕金森氏病（PD）和路易小体痴呆症（DLB）的病理标志。α-突触核蛋白内含物主要存在于神经元中，但也经常出现在星形胶质细胞中。然而，星形胶质细胞中α-突触核蛋白包涵体的病理学意义以及神经胶质细胞清除有毒α-突触核蛋白种类的能力仍然未知。在本研究中，我们调查了初级神经元，星形胶质细胞和少突胶质细胞共培养系统中寡聚α-突触核蛋白的摄取，降解和毒性作用。发现α-突触核蛋白寡聚物与神经胶质细胞共定位，并且发现星形胶质细胞内化特别大量的蛋白质。摄取后 星形胶质细胞开始通过溶酶体途径降解寡聚体，但是由于不完全消化，仍然保留了大量的细胞内沉积物。此外，星形胶质细胞显示线粒体异常。两者合计，我们的数据表明星形胶质细胞在清除细胞外空间中有毒α-突触核蛋白物种中起重要作用。然而，当它们的降解能力负担过重时，α-突触核蛋白沉积物会持续存在并导致有害的细胞过程。