Tau病理学
神经科学
病理
片段(逻辑)
医学
化学
心理学
疾病
计算机科学
阿尔茨海默病
程序设计语言
作者
Hao Yu,Min Xiong,Congcong Liu,Danhao Xia,Lanxia Meng,Zhentao Zhang
标识
DOI:10.3389/fnagi.2023.1241750
摘要
Tau 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.The 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.Full-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.The 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).The 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.
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