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Early growth response-1 regulates acetylcholinesterase and its relation with the course of Alzheimer's disease. / Hu, Yu-Ting; Chen, Xin-Lu; Huang, Shu-Han; Zhu, Qiong-Bin; Yu, Si-Yang; Shen, Yi; Sluiter, Arja; Verhaagen, Joost; Zhao, Juan; Swaab, Dick; Bao, Ai-Min.

In: Brain Pathology, 03.12.2018.

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Harvard

APA

Hu, Y-T., Chen, X-L., Huang, S-H., Zhu, Q-B., Yu, S-Y., Shen, Y., ... Bao, A-M. (2018). Early growth response-1 regulates acetylcholinesterase and its relation with the course of Alzheimer's disease. Brain Pathology. DOI: 10.1111/bpa.12688

Vancouver

Hu Y-T, Chen X-L, Huang S-H, Zhu Q-B, Yu S-Y, Shen Y et al. Early growth response-1 regulates acetylcholinesterase and its relation with the course of Alzheimer's disease. Brain Pathology. 2018 Dec 3. Available from, DOI: 10.1111/bpa.12688

Author

BibTeX

@article{763091a9e9ae458cb3ea84c55511bd3f,
title = "Early growth response-1 regulates acetylcholinesterase and its relation with the course of Alzheimer's disease",
abstract = "Our previous studies showed that the transcription factor early growth response-1 (EGR1) may play a role in keeping the brain cholinergic function intact in the preclinical stages of Alzheimer's disease (AD). In order to elucidate the mechanisms involved, we first performed data mining on our previous microarray study on postmortem human prefrontal cortex (PFC) for the changes in the expression of EGR1 and acetylcholinesterase (AChE) and the relationship between them during the course of AD. The study contained 49 patients, ranging from non-demented controls (Braak stage 0) to late AD patients (Braak stage VI). We found EGR1-mRNA was high in early AD and decreased in late AD stages, while AChE-mRNA was stable in preclinical AD and slightly decreased in late AD stages. A significant positive correlation was found between the mRNA levels of these two molecules. In addition, we studied the relationship between EGR1 and AChE mRNA levels in the frontal cortex of 3-12-months old triple-transgenic AD (3xTg-AD) mice. EGR1- and AChE-mRNA were lower in 3xTg-AD mice compared with wild type (WT) mice. A significant positive correlation between these two molecules was present in the entire group and in each age group of either WT or 3xTg-AD mice. Subsequently, AChE expression was determined following up- or down-regulating EGR1 in cell lines and the EGR1 levels were found to regulate AChE at both the mRNA and protein levels. Dual-luciferase assay and electrophoretic mobility shift assay in the EGR1-overexpressing cells were performed to determine the functionally effective binding sites of the EGR1 on the AChE gene promoter. We conclude that the EGR1 can upregulate AChE expression by a direct effect on its gene promoter, which may contribute significantly to the changes in cholinergic function in the course of AD. The 3xTg-AD mouse model only reflects later stage AD. This article is protected by copyright. All rights reserved.",
author = "Yu-Ting Hu and Xin-Lu Chen and Shu-Han Huang and Qiong-Bin Zhu and Si-Yang Yu and Yi Shen and Arja Sluiter and Joost Verhaagen and Juan Zhao and Dick Swaab and Ai-Min Bao",
note = "This article is protected by copyright. All rights reserved.",
year = "2018",
month = "12",
day = "3",
doi = "10.1111/bpa.12688",
language = "English",
journal = "Brain Pathology",
issn = "1015-6305",
publisher = "Wiley-Blackwell",

}

RIS

TY - JOUR

T1 - Early growth response-1 regulates acetylcholinesterase and its relation with the course of Alzheimer's disease

AU - Hu,Yu-Ting

AU - Chen,Xin-Lu

AU - Huang,Shu-Han

AU - Zhu,Qiong-Bin

AU - Yu,Si-Yang

AU - Shen,Yi

AU - Sluiter,Arja

AU - Verhaagen,Joost

AU - Zhao,Juan

AU - Swaab,Dick

AU - Bao,Ai-Min

N1 - This article is protected by copyright. All rights reserved.

PY - 2018/12/3

Y1 - 2018/12/3

N2 - Our previous studies showed that the transcription factor early growth response-1 (EGR1) may play a role in keeping the brain cholinergic function intact in the preclinical stages of Alzheimer's disease (AD). In order to elucidate the mechanisms involved, we first performed data mining on our previous microarray study on postmortem human prefrontal cortex (PFC) for the changes in the expression of EGR1 and acetylcholinesterase (AChE) and the relationship between them during the course of AD. The study contained 49 patients, ranging from non-demented controls (Braak stage 0) to late AD patients (Braak stage VI). We found EGR1-mRNA was high in early AD and decreased in late AD stages, while AChE-mRNA was stable in preclinical AD and slightly decreased in late AD stages. A significant positive correlation was found between the mRNA levels of these two molecules. In addition, we studied the relationship between EGR1 and AChE mRNA levels in the frontal cortex of 3-12-months old triple-transgenic AD (3xTg-AD) mice. EGR1- and AChE-mRNA were lower in 3xTg-AD mice compared with wild type (WT) mice. A significant positive correlation between these two molecules was present in the entire group and in each age group of either WT or 3xTg-AD mice. Subsequently, AChE expression was determined following up- or down-regulating EGR1 in cell lines and the EGR1 levels were found to regulate AChE at both the mRNA and protein levels. Dual-luciferase assay and electrophoretic mobility shift assay in the EGR1-overexpressing cells were performed to determine the functionally effective binding sites of the EGR1 on the AChE gene promoter. We conclude that the EGR1 can upregulate AChE expression by a direct effect on its gene promoter, which may contribute significantly to the changes in cholinergic function in the course of AD. The 3xTg-AD mouse model only reflects later stage AD. This article is protected by copyright. All rights reserved.

AB - Our previous studies showed that the transcription factor early growth response-1 (EGR1) may play a role in keeping the brain cholinergic function intact in the preclinical stages of Alzheimer's disease (AD). In order to elucidate the mechanisms involved, we first performed data mining on our previous microarray study on postmortem human prefrontal cortex (PFC) for the changes in the expression of EGR1 and acetylcholinesterase (AChE) and the relationship between them during the course of AD. The study contained 49 patients, ranging from non-demented controls (Braak stage 0) to late AD patients (Braak stage VI). We found EGR1-mRNA was high in early AD and decreased in late AD stages, while AChE-mRNA was stable in preclinical AD and slightly decreased in late AD stages. A significant positive correlation was found between the mRNA levels of these two molecules. In addition, we studied the relationship between EGR1 and AChE mRNA levels in the frontal cortex of 3-12-months old triple-transgenic AD (3xTg-AD) mice. EGR1- and AChE-mRNA were lower in 3xTg-AD mice compared with wild type (WT) mice. A significant positive correlation between these two molecules was present in the entire group and in each age group of either WT or 3xTg-AD mice. Subsequently, AChE expression was determined following up- or down-regulating EGR1 in cell lines and the EGR1 levels were found to regulate AChE at both the mRNA and protein levels. Dual-luciferase assay and electrophoretic mobility shift assay in the EGR1-overexpressing cells were performed to determine the functionally effective binding sites of the EGR1 on the AChE gene promoter. We conclude that the EGR1 can upregulate AChE expression by a direct effect on its gene promoter, which may contribute significantly to the changes in cholinergic function in the course of AD. The 3xTg-AD mouse model only reflects later stage AD. This article is protected by copyright. All rights reserved.

U2 - 10.1111/bpa.12688

DO - 10.1111/bpa.12688

M3 - Article

JO - Brain Pathology

T2 - Brain Pathology

JF - Brain Pathology

SN - 1015-6305

ER -

ID: 9109952