The γ-Adducin 1–357 fragment promotes tau pathology

Frontiers in Aging Neuroscience

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.