title: Role of miR-211 in Neuronal Differentiation and Viability: Implications to Pathogenesis of Alzheimer's Disease.
abstract: Alzheimer's disease (AD) is an age-related irreversible neurodegenerative disorder characterized by extracellular β Amyloid(Aβ) deposition, intracellular neurofibrillary tangles and neuronal loss. The dysfunction of neurogenesis and increased degeneration of neurons contribute to the pathogenesis of AD. We now report that miR-211-5p, a small non-coding RNA, can impair neurite differentiation by directly targeting NUAK1, decrease neuronal viability and accelerate the progression of Aβ-induced pathologies. In this study, we observed that during embryonic development, the expression levels of miR-211-5p were down-regulated in the normal cerebral cortexes of mice. However, in APPswe/PS1ΔE9 double transgenic adult mice, it was up-regulated from 9 months of age compared to that of the age-matched wild type mice. Studies in primary cortical neuron cultures demonstrated that miR-211-5p can inhibit neurite growth and branching via NUAK1 repression and decrease mature neuron viability. The impairments were more obvious under the action of Aβ. Our data showed that miR-211-5p could inhibit cortical neuron differentiation and survival, which may contribute to the synaptic failure, neuronal loss and cognitive dysfunction in AD.
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: Chunying
authors.initials: C
authors.lastname: Fan
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: Hongxue
authors.initials: H
authors.lastname: Luo
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: Dongdong
authors.initials: D
authors.lastname: Yan
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: Ludwig Institute for Cancer Research, La Jolla CA, USA.
authors.forename: Yarui
authors.initials: Y
authors.lastname: Diao
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); NUAK1; amyloid β (Aβ); microRNA-211-5p; neurite branching; neuronal viability