Autor: |
Kai-Jie He, Jin-Bao Zhang, Jun-Yi Liu, Feng-Lun Zhao, Xiao-Yu Yao, Yu-Ting Tang, Jin-Ru Zhang, Xiao-Yu Cheng, Li-Fang Hu, Fen Wang, Chun-Feng Liu |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
|
Zdroj: |
iScience, Vol 26, Iss 11, Pp 108130- (2023) |
Druh dokumentu: |
article |
ISSN: |
2589-0042 |
DOI: |
10.1016/j.isci.2023.108130 |
Popis: |
Summary: 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 Leucine-Rich Repeat Kinase 2 (LRRK2) are also genetically linked to PD and neuroinflammation. However, how O-αS and LRRK2 interact in glial cells remains unclear. Here, we reported that LRRK2 G2019S mutation, which is one of the most frequent causes of familial PD, enhanced the effects of O-αS on astrocytes both in vivo and in vitro. Meanwhile, inhibition of LRRK2 kinase activity could relieve the inflammatory effects of both LRRK2 G2019S 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 LRRK2 kinase activity may be a viable strategy for suppressing neuroinflammation in PD. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
|