The protective role of microRNA-200c in Alzheimer’s disease pathologies is induced by beta Amyloid-triggered Endoplasmic Reticulum Stress
MicroRNAs are small non-coding RNAs that repress the expression of their target proteins. The roles of microRNAs in the development of Alzheimer’s disease (AD) are not clear. In this study we show that miR-200c represses the expression of PTEN protein. PTEN downregulation by miR-200c supports the su...
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doaj-8c820e5858e4431d92c054d06362573c2020-11-24T22:17:04ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992016-12-01910.3389/fnmol.2016.00140218225The protective role of microRNA-200c in Alzheimer’s disease pathologies is induced by beta Amyloid-triggered Endoplasmic Reticulum StressQi Wu0Xiaoyang Ye1Yi Xiong2Haili Zhu3Jianting Miao4Wei Zhang5Jun Wan6Jun Wan7Shenzhen Peking University-the Hong Kong University of Science and Technology Medical CenterShenzhen Peking University-the Hong Kong University of Science and Technology Medical CenterShenzhen Peking University-the Hong Kong University of Science and Technology Medical CenterShenzhen Peking University-the Hong Kong University of Science and Technology Medical CenterTangdu Hospital, Fourth Military Medical UniversityShenzhen Peking University-the Hong Kong University of Science and Technology Medical CenterShenzhen Peking University-the Hong Kong University of Science and Technology Medical CenterThe Hong Kong University of Science and TechnologyMicroRNAs are small non-coding RNAs that repress the expression of their target proteins. The roles of microRNAs in the development of Alzheimer’s disease (AD) are not clear. In this study we show that miR-200c represses the expression of PTEN protein. PTEN downregulation by miR-200c supports the survival and differentiation of cultured neurons. AD is a progressive neurodegenerative disease signified by beta amyloid (Aβ) peptide aggregation and deposition. In a mouse model of AD that is induced by APPswe and PS1ΔE9 double transgenes, we found Aβ deposition results in neuronal ER stress that induces miR200c. Pharmacological blockade of ER stress inhibited Aβ-induced miR-200c overexpression in AD brains. MiR-200c was detected in the serum of both AD mice and human AD patients. These findings suggest that miR-200c functions as part of the neuronal cell-intrinsic adaptive machinery, and supports neuronal survival and differentiation in response to Aβ induced ER-stress by downregulating PTEN.http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00140/fullmicroRNAPtenAlzheimer’s disease (AD)MiR-200cBeta amyloid peptideEndoplasmic reticulum stress (ER stress) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qi Wu Xiaoyang Ye Yi Xiong Haili Zhu Jianting Miao Wei Zhang Jun Wan Jun Wan |
spellingShingle |
Qi Wu Xiaoyang Ye Yi Xiong Haili Zhu Jianting Miao Wei Zhang Jun Wan Jun Wan The protective role of microRNA-200c in Alzheimer’s disease pathologies is induced by beta Amyloid-triggered Endoplasmic Reticulum Stress Frontiers in Molecular Neuroscience microRNA Pten Alzheimer’s disease (AD) MiR-200c Beta amyloid peptide Endoplasmic reticulum stress (ER stress) |
author_facet |
Qi Wu Xiaoyang Ye Yi Xiong Haili Zhu Jianting Miao Wei Zhang Jun Wan Jun Wan |
author_sort |
Qi Wu |
title |
The protective role of microRNA-200c in Alzheimer’s disease pathologies is induced by beta Amyloid-triggered Endoplasmic Reticulum Stress |
title_short |
The protective role of microRNA-200c in Alzheimer’s disease pathologies is induced by beta Amyloid-triggered Endoplasmic Reticulum Stress |
title_full |
The protective role of microRNA-200c in Alzheimer’s disease pathologies is induced by beta Amyloid-triggered Endoplasmic Reticulum Stress |
title_fullStr |
The protective role of microRNA-200c in Alzheimer’s disease pathologies is induced by beta Amyloid-triggered Endoplasmic Reticulum Stress |
title_full_unstemmed |
The protective role of microRNA-200c in Alzheimer’s disease pathologies is induced by beta Amyloid-triggered Endoplasmic Reticulum Stress |
title_sort |
protective role of microrna-200c in alzheimer’s disease pathologies is induced by beta amyloid-triggered endoplasmic reticulum stress |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Neuroscience |
issn |
1662-5099 |
publishDate |
2016-12-01 |
description |
MicroRNAs are small non-coding RNAs that repress the expression of their target proteins. The roles of microRNAs in the development of Alzheimer’s disease (AD) are not clear. In this study we show that miR-200c represses the expression of PTEN protein. PTEN downregulation by miR-200c supports the survival and differentiation of cultured neurons. AD is a progressive neurodegenerative disease signified by beta amyloid (Aβ) peptide aggregation and deposition. In a mouse model of AD that is induced by APPswe and PS1ΔE9 double transgenes, we found Aβ deposition results in neuronal ER stress that induces miR200c. Pharmacological blockade of ER stress inhibited Aβ-induced miR-200c overexpression in AD brains. MiR-200c was detected in the serum of both AD mice and human AD patients. These findings suggest that miR-200c functions as part of the neuronal cell-intrinsic adaptive machinery, and supports neuronal survival and differentiation in response to Aβ induced ER-stress by downregulating PTEN. |
topic |
microRNA Pten Alzheimer’s disease (AD) MiR-200c Beta amyloid peptide Endoplasmic reticulum stress (ER stress) |
url |
http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00140/full |
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