He Kai-Jie, Zhang Jin-Bao, Liu Jun-Yi, Zhao Feng-Lun, Yao Xiao-Yu, Tang Yu-Ting, Zhang Jin-Ru, Cheng Xiao-Yu, Hu Li-Fang, Wang Fen, Liu Chun-Feng
Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China.
iScience. 2023 Oct 5;26(11):108130. doi: 10.1016/j.isci.2023.108130. eCollection 2023 Nov 17.
Parkinson's disease (PD) is characterized by the irreversible loss of dopaminergic neurons and the accumulation of α-synuclein in Lewy bodies. The oligomeric α-synuclein (O-αS) is the most toxic form of α-synuclein species, and it has been reported to be a robust inflammatory mediator. Mutations in () are also genetically linked to PD and neuroinflammation. However, how O-αS and LRRK2 interact in glial cells remains unclear. Here, we reported that mutation, which is one of the most frequent causes of familial PD, enhanced the effects of O-αS on astrocytes both and . Meanwhile, inhibition of LRRK2 kinase activity could relieve the inflammatory effects of both and O-αS. We also demonstrated that nuclear factor κB (NF-κB) pathway might be involved in the neuroinflammatory responses. These findings revealed that inhibition of kinase activity may be a viable strategy for suppressing neuroinflammation in PD.
帕金森病（PD）的特征是多巴胺能神经元的不可逆丧失以及路易小体中α-突触核蛋白的积累。寡聚α-突触核蛋白（O-αS）是α-突触核蛋白最具毒性的形式，据报道它是一种强大的炎症介质。（）中的突变也与帕金森病和神经炎症存在遗传联系。然而，O-αS和富含亮氨酸重复激酶2（LRRK2）在神经胶质细胞中如何相互作用仍不清楚。在此，我们报告称，作为家族性帕金森病最常见病因之一的（）突变，在（）和（）方面均增强了O-αS对星形胶质细胞的作用。同时，抑制LRRK2激酶活性可减轻（）和O-αS的炎症效应。我们还证明核因子κB（NF-κB）通路可能参与神经炎症反应。这些发现表明，抑制（）激酶活性可能是抑制帕金森病神经炎症的一种可行策略。
