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The γ-Adducin 1–357 fragment promotes tau pathology

BACKGROUND: 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. OBJECTIVE: The aim of this project is to...

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Autores principales: Yu, Honglu, Xiong, Min, Liu, Congcong, Xia, Danhao, Meng, Lanxia, Zhang, Zhentao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526357/
https://www.ncbi.nlm.nih.gov/pubmed/37771520
http://dx.doi.org/10.3389/fnagi.2023.1241750
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author Yu, Honglu
Xiong, Min
Liu, Congcong
Xia, Danhao
Meng, Lanxia
Zhang, Zhentao
author_facet Yu, Honglu
Xiong, Min
Liu, Congcong
Xia, Danhao
Meng, Lanxia
Zhang, Zhentao
author_sort Yu, Honglu
collection PubMed
description BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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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spelling pubmed-105263572023-09-28 The γ-Adducin 1–357 fragment promotes tau pathology Yu, Honglu Xiong, Min Liu, Congcong Xia, Danhao Meng, Lanxia Zhang, Zhentao Front Aging Neurosci Aging Neuroscience BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. Frontiers Media S.A. 2023-09-13 /pmc/articles/PMC10526357/ /pubmed/37771520 http://dx.doi.org/10.3389/fnagi.2023.1241750 Text en Copyright © 2023 Yu, Xiong, Liu, Xia, Meng and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging Neuroscience
Yu, Honglu
Xiong, Min
Liu, Congcong
Xia, Danhao
Meng, Lanxia
Zhang, Zhentao
The γ-Adducin 1–357 fragment promotes tau pathology
title The γ-Adducin 1–357 fragment promotes tau pathology
title_full The γ-Adducin 1–357 fragment promotes tau pathology
title_fullStr The γ-Adducin 1–357 fragment promotes tau pathology
title_full_unstemmed The γ-Adducin 1–357 fragment promotes tau pathology
title_short The γ-Adducin 1–357 fragment promotes tau pathology
title_sort γ-adducin 1–357 fragment promotes tau pathology
topic Aging Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526357/
https://www.ncbi.nlm.nih.gov/pubmed/37771520
http://dx.doi.org/10.3389/fnagi.2023.1241750
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