The principal hallmark of Parkinson’s disease (PD) is the selective neurodegeneration of dopaminergic neurones. Mounting evidence suggests that astrocytes may contribute to dopaminergic neurodegeneration through decreased homoeostatic support and deficient neuroprotection. In this study, we generated induced pluripotent stem cells (iPSC)-derived astrocytes from PD patients with LRRK2^(G2019S) mutation and healthy donors of the similar age. In cell lines derived from PD patients, astrocytes were characterised by a significant decrease in S100B and GFAP-positive astrocytic profiles associated with marked decrease in astrocyte complexity. In addition, PD-derived astrocytes demonstrated aberrant mitochondrial morphology, decreased mitochondrial activity and ATP production along with an increase of glycolysis and increased production of reactive oxygen species. Taken together, our data indicate that astrocytic asthenia observed in patient-derived cultures with LRRK2^(G2019S) mutation may contribute to neuronal death through decreased homoeostatic support, elevated oxidative stress and failed neuroprotection.

帕金森病 (PD) 的主要标志是多巴胺能神经元的选择性神经变性。越来越多的证据表明，星形胶质细胞可能通过降低稳态支持和缺乏神经保护来促进多巴胺能神经变性。^{在这项研究中，我们从具有 LRRK2 (G2019S)}的 PD 患者中生成了诱导多能干细胞 (iPSC) 衍生的星形胶质细胞年龄相近的突变和健康供体。在源自 PD 患者的细胞系中，星形胶质细胞的特征是 S100B 和 GFAP 阳性星形胶质细胞谱显着降低，与星形胶质细胞复杂性显着降低相关。此外，PD 衍生的星形胶质细胞表现出异常的线粒体形态、线粒体活性和 ATP 产生降低以及糖酵解增加和活性氧产生增加。综上所述，我们的数据表明，在具有 LRRK2 ^(G2019S)突变的患者来源的培养物中观察到的星形胶质细胞无力可能通过降低稳态支持、升高氧化应激和神经保护失败而导致神经元死亡。