Department of Pharmaceutical Science, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
Cells. 2023 Feb 15;12(4):622. doi: 10.3390/cells12040622.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the aggregation of Lewy bodies in the basal ganglia, resulting in movement impairment referred to as parkinsonism. However, the etiology of PD is not well known, with genetic factors accounting only for 10-15% of all PD cases. The pathogenetic mechanism of PD is not completely understood, although several mechanisms, such as oxidative stress and inflammation, have been suggested. Understanding the mechanisms of PD pathogenesis is critical for developing highly efficacious therapeutics. In the PD brain, dopaminergic neurons degenerate mainly in the basal ganglia, but recently emerging evidence has shown that astrocytes also significantly contribute to dopaminergic neuronal death. In this review, we discuss the role of astrocytes in PD pathogenesis due to mutations in α-synuclein (PARK1), DJ-1 (PARK7), parkin (PARK2), leucine-rich repeat kinase 2 (LRRK2, PARK8), and PTEN-induced kinase 1 (PINK1, PARK6). We also discuss PD experimental models using neurotoxins, such as paraquat, rotenone, 6-hydroxydopamine, and MPTP/MPP+. A more precise and comprehensive understanding of astrocytes' modulatory roles in dopaminergic neurodegeneration in PD will help develop novel strategies for effective PD therapeutics.
帕金森病（PD）是一种神经退行性疾病，其特征是基底神经节中多巴胺能神经元的丧失和路易体的聚集，导致运动障碍，即帕金森症。然而，PD 的病因尚不清楚，遗传因素仅占所有 PD 病例的 10-15%。PD 的发病机制尚不完全清楚，尽管已经提出了几种机制，如氧化应激和炎症。了解 PD 发病机制对于开发高效治疗方法至关重要。在 PD 大脑中，多巴胺能神经元主要在基底神经节中退化，但最近出现的证据表明，星形胶质细胞也对多巴胺能神经元死亡有重要贡献。在这篇综述中，我们讨论了由于α-突触核蛋白（PARK1）、DJ-1（PARK7）、parkin（PARK2）、富含亮氨酸重复激酶 2（LRRK2，PARK8）和 PTEN 诱导的激酶 1（PINK1，PARK6）突变引起的星形胶质细胞在 PD 发病机制中的作用。我们还讨论了使用神经毒素（如百草枯、鱼藤酮、6-羟多巴胺和 MPTP/MPP+）的 PD 实验模型。更精确和全面地了解星形胶质细胞在 PD 中多巴胺能神经退行性变中的调节作用将有助于开发有效的 PD 治疗新策略。
