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Cycloheximide Treatment Causes a ZVAD-Sensitive Protease-Dependent Cleavage of Human Tau in Drosophila Cells

Neurofibrillary tangles are the main pathological feature of Alzheimer’s disease. Insoluble tau protein is the major component of neurofibrillary tangles. Defects in the tau protein degradation pathway in neurons can lead to the accumulation of tau and its subsequent aggregation. Currently, contradi...

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Detalles Bibliográficos
Autores principales: Geng, Junhua, Xia, Lu, Li, Wanjie, Zhao, Changqi, Dou, Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927919/
https://www.ncbi.nlm.nih.gov/pubmed/26599052
http://dx.doi.org/10.3233/JAD-150423
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author Geng, Junhua
Xia, Lu
Li, Wanjie
Zhao, Changqi
Dou, Fei
author_facet Geng, Junhua
Xia, Lu
Li, Wanjie
Zhao, Changqi
Dou, Fei
author_sort Geng, Junhua
collection PubMed
description Neurofibrillary tangles are the main pathological feature of Alzheimer’s disease. Insoluble tau protein is the major component of neurofibrillary tangles. Defects in the tau protein degradation pathway in neurons can lead to the accumulation of tau and its subsequent aggregation. Currently, contradictory results on the tau degradation pathway have been reported by different groups. This discrepancy is most likely due to different cell lines and methods used in those studies. In this study, we found that cycloheximide treatment induced mild activation of a ZVAD-sensitive protease in Drosophila Kc cells, resulting in cleavage of tau at its C-terminus; this cleavage could generate misleading tau protein degradation pattern results depending on the antibodies used in the assay. Because cycloheximide is a broadly used chemical reagent for the study of protein degradation, the unexpected artificial effect we observed here indicates that cycloheximide is not suitable for the study of tau degradation. Other methods, such as inducible expression systems and pulse-chase assays, may be more appropriate for studying tau degradation under physiological conditions.
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spelling pubmed-49279192016-06-30 Cycloheximide Treatment Causes a ZVAD-Sensitive Protease-Dependent Cleavage of Human Tau in Drosophila Cells Geng, Junhua Xia, Lu Li, Wanjie Zhao, Changqi Dou, Fei J Alzheimers Dis Research Article Neurofibrillary tangles are the main pathological feature of Alzheimer’s disease. Insoluble tau protein is the major component of neurofibrillary tangles. Defects in the tau protein degradation pathway in neurons can lead to the accumulation of tau and its subsequent aggregation. Currently, contradictory results on the tau degradation pathway have been reported by different groups. This discrepancy is most likely due to different cell lines and methods used in those studies. In this study, we found that cycloheximide treatment induced mild activation of a ZVAD-sensitive protease in Drosophila Kc cells, resulting in cleavage of tau at its C-terminus; this cleavage could generate misleading tau protein degradation pattern results depending on the antibodies used in the assay. Because cycloheximide is a broadly used chemical reagent for the study of protein degradation, the unexpected artificial effect we observed here indicates that cycloheximide is not suitable for the study of tau degradation. Other methods, such as inducible expression systems and pulse-chase assays, may be more appropriate for studying tau degradation under physiological conditions. IOS Press 2015-11-22 /pmc/articles/PMC4927919/ /pubmed/26599052 http://dx.doi.org/10.3233/JAD-150423 Text en IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Geng, Junhua
Xia, Lu
Li, Wanjie
Zhao, Changqi
Dou, Fei
Cycloheximide Treatment Causes a ZVAD-Sensitive Protease-Dependent Cleavage of Human Tau in Drosophila Cells
title Cycloheximide Treatment Causes a ZVAD-Sensitive Protease-Dependent Cleavage of Human Tau in Drosophila Cells
title_full Cycloheximide Treatment Causes a ZVAD-Sensitive Protease-Dependent Cleavage of Human Tau in Drosophila Cells
title_fullStr Cycloheximide Treatment Causes a ZVAD-Sensitive Protease-Dependent Cleavage of Human Tau in Drosophila Cells
title_full_unstemmed Cycloheximide Treatment Causes a ZVAD-Sensitive Protease-Dependent Cleavage of Human Tau in Drosophila Cells
title_short Cycloheximide Treatment Causes a ZVAD-Sensitive Protease-Dependent Cleavage of Human Tau in Drosophila Cells
title_sort cycloheximide treatment causes a zvad-sensitive protease-dependent cleavage of human tau in drosophila cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927919/
https://www.ncbi.nlm.nih.gov/pubmed/26599052
http://dx.doi.org/10.3233/JAD-150423
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