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Effect of p62 on tau hyperphosphorylation in a rat model of Alzheimer's disease☆

Tau hyperphosphorylation is a main cause of neuronal loss in Alzheimer's disease, which can be caused by many factors, including oxidative stress. The multifunctional protein p62, which exists in neurofibrillary tangles and causes aggregation of hyperphosphorylated tau, not only serves as a rec...

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Autores principales: Zheng, Xianhong, Wang, Weiwei, Liu, Ruizhi, Huang, Honglan, Zhang, Rihui, Sun, Liankun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308800/
https://www.ncbi.nlm.nih.gov/pubmed/25657660
http://dx.doi.org/10.3969/j.issn.1673-5374.2012.17.004
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author Zheng, Xianhong
Wang, Weiwei
Liu, Ruizhi
Huang, Honglan
Zhang, Rihui
Sun, Liankun
author_facet Zheng, Xianhong
Wang, Weiwei
Liu, Ruizhi
Huang, Honglan
Zhang, Rihui
Sun, Liankun
author_sort Zheng, Xianhong
collection PubMed
description Tau hyperphosphorylation is a main cause of neuronal loss in Alzheimer's disease, which can be caused by many factors, including oxidative stress. The multifunctional protein p62, which exists in neurofibrillary tangles and causes aggregation of hyperphosphorylated tau, not only serves as a receptor in selective autophagy, but also regulates oxidative stress. However, whether p62 participates in oxidative stress-induced tau hyperphosphorylation remains unclear. In this study, we produced an Alzheimer's disease rat model by injecting β-amyloid protein into the hippocampus and β-galactose intraperitoneally. Hematoxylin-eosin staining was used for morphological analysis of brain tissue, and western blotting, immunohistochemistry and reverse transcription-PCR were employed to study p62 and autophagy related proteins, antioxidant defense system kelch-like ECH-associated protein 1-NF-E2-related factor 2 related proteins and hyperphosphorylated tau, respectively. The number of neurons in the brain decreased in Alzheimer's disease rats, and the autophagy related proteins Atg12-Atg5, microtubule-associated protein 1 light chain 3-phosphatidylethanolamine and Beclin1 increased significantly, while p62 expression reduced. Expression of kelch-like ECH-associated protein 1 increased, NF-E2-related factor 2 protein and the downstream gene products of glutamate cysteine ligase catalytic subunit and glutamate cysteine ligase modulatory subunit decreased, and hyperphosphorylated tau increased. These findings demonstrate that autophagy levels increased and p62 levels decreased in the brains of Alzheimer's disease rats. Moreover, the anti-oxidative capability of the NF-E2-related factor 2-antioxidant response element pathway was decreased, which may be the cause of tau hyperphosphorylation in Alzheimer's disease brain tissue and the subsequent structural and functional damage to neurons.
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spelling pubmed-43088002015-02-05 Effect of p62 on tau hyperphosphorylation in a rat model of Alzheimer's disease☆ Zheng, Xianhong Wang, Weiwei Liu, Ruizhi Huang, Honglan Zhang, Rihui Sun, Liankun Neural Regen Res Research and Report: Peripheral Nerve Injury and Neural Regeneration Tau hyperphosphorylation is a main cause of neuronal loss in Alzheimer's disease, which can be caused by many factors, including oxidative stress. The multifunctional protein p62, which exists in neurofibrillary tangles and causes aggregation of hyperphosphorylated tau, not only serves as a receptor in selective autophagy, but also regulates oxidative stress. However, whether p62 participates in oxidative stress-induced tau hyperphosphorylation remains unclear. In this study, we produced an Alzheimer's disease rat model by injecting β-amyloid protein into the hippocampus and β-galactose intraperitoneally. Hematoxylin-eosin staining was used for morphological analysis of brain tissue, and western blotting, immunohistochemistry and reverse transcription-PCR were employed to study p62 and autophagy related proteins, antioxidant defense system kelch-like ECH-associated protein 1-NF-E2-related factor 2 related proteins and hyperphosphorylated tau, respectively. The number of neurons in the brain decreased in Alzheimer's disease rats, and the autophagy related proteins Atg12-Atg5, microtubule-associated protein 1 light chain 3-phosphatidylethanolamine and Beclin1 increased significantly, while p62 expression reduced. Expression of kelch-like ECH-associated protein 1 increased, NF-E2-related factor 2 protein and the downstream gene products of glutamate cysteine ligase catalytic subunit and glutamate cysteine ligase modulatory subunit decreased, and hyperphosphorylated tau increased. These findings demonstrate that autophagy levels increased and p62 levels decreased in the brains of Alzheimer's disease rats. Moreover, the anti-oxidative capability of the NF-E2-related factor 2-antioxidant response element pathway was decreased, which may be the cause of tau hyperphosphorylation in Alzheimer's disease brain tissue and the subsequent structural and functional damage to neurons. Medknow Publications & Media Pvt Ltd 2012-06-15 /pmc/articles/PMC4308800/ /pubmed/25657660 http://dx.doi.org/10.3969/j.issn.1673-5374.2012.17.004 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research and Report: Peripheral Nerve Injury and Neural Regeneration
Zheng, Xianhong
Wang, Weiwei
Liu, Ruizhi
Huang, Honglan
Zhang, Rihui
Sun, Liankun
Effect of p62 on tau hyperphosphorylation in a rat model of Alzheimer's disease☆
title Effect of p62 on tau hyperphosphorylation in a rat model of Alzheimer's disease☆
title_full Effect of p62 on tau hyperphosphorylation in a rat model of Alzheimer's disease☆
title_fullStr Effect of p62 on tau hyperphosphorylation in a rat model of Alzheimer's disease☆
title_full_unstemmed Effect of p62 on tau hyperphosphorylation in a rat model of Alzheimer's disease☆
title_short Effect of p62 on tau hyperphosphorylation in a rat model of Alzheimer's disease☆
title_sort effect of p62 on tau hyperphosphorylation in a rat model of alzheimer's disease☆
topic Research and Report: Peripheral Nerve Injury and Neural Regeneration
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308800/
https://www.ncbi.nlm.nih.gov/pubmed/25657660
http://dx.doi.org/10.3969/j.issn.1673-5374.2012.17.004
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