title: The Protective Role of microRNA-200c in Alzheimer's Disease Pathologies Is Induced by Beta Amyloid-Triggered Endoplasmic Reticulum Stress.
abstract: 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 byAPPsweandPS1ΔE9double 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.
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center Shenzhen, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center Shenzhen, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Ye
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center Shenzhen, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center Shenzhen, China.
authors.forename: Haili
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Tangdu Hospital, Fourth Military Medical University Xi'an City, China.
authors.forename: Jianting
authors.initials: J
authors.lastname: Miao
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center Shenzhen, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical CenterShenzhen, China; Division of Life Science, The Hong Kong University of Science and TechnologyHong Kong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wan
keywords: Alzheimer's disease (AD); PTEN; beta amyloid peptide (Aβ); endoplasmic reticulum stress (ER stress); miR-200c; microRNA