Frontiers in Aging Neuroscience | |
The γ-Adducin 1–357 fragment promotes tau pathology | |
Aging Neuroscience | |
Honglu Yu1  Lanxia Meng1  Congcong Liu1  Danhao Xia1  Min Xiong1  Zhentao Zhang2  | |
[1] Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China;Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China;TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; | |
关键词: Alzheimer’s disease; γ-adducin; tau phosphorylation; glycogen synthase kinase-3β; 4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione; | |
DOI : 10.3389/fnagi.2023.1241750 | |
received in 2023-06-17, accepted in 2023-08-28, 发布年份 2023 | |
来源: Frontiers | |
【 摘 要 】
BackgroundTau phosphorylation is a pathological hallmark of Alzheimer’s disease (AD). Previously, we reported that the γ-adducin 1–357 fragment is present in the brains of AD patients. However, it remains unknown how γ-adducin regulates tau phosphorylation.ObjectiveThe aim of this project is to investigate the effects of the γ-adducin 1–357 fragment on tau phosphorylation and the kinases involved in this process.MethodsFull-length γ-adducin or the γ-adducin 1–357 fragment was expressed in HEK293 cells, SH-SY5Y cells, and primary neurons. The phosphorylation of tau Ser396 was determined using Western blot and immunofluorescence. Tau P301S transgenic mice were injected with adeno-associated virus encoding full-length γ-adducin or γ-adducin 1–357 fragment to determine the phosphorylation of tau.ResultsThe γ-adducin 1–357 fragment enhances tau phosphorylation at Ser396. Additionally, the expression of the γ-adducin 1–357 fragment leads to the activation of glycogen synthase kinase-3β (GSK-3β). This effect was mitigated by the GSK-3β inhibitor 4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8).ConclusionThe γ-adducin 1–357 fragment enhances tau phosphorylation by activating GSK3β. These results support that the fragmentation of γ-adducin may play a pivotal role in tau pathology.
【 授权许可】
Unknown
Copyright © 2023 Yu, Xiong, Liu, Xia, Meng and Zhang.
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