Role of miR-211 in Neuronal Differentiation and Viability: Implications to Pathogenesis of Alzheimer's Disease.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Fan, C; Wu, Q; Ye, X; Luo, H; Yan, D; Xiong, Y; Zhu, H; Diao, Y; Zhang, W; Wan, J

Published Date

  • 2016

Published In

Volume / Issue

  • 8 /

Start / End Page

  • 166 -

PubMed ID

  • 27458373

Pubmed Central ID

  • PMC4937029

International Standard Serial Number (ISSN)

  • 1663-4365

Digital Object Identifier (DOI)

  • 10.3389/fnagi.2016.00166

Language

  • eng

Conference Location

  • Switzerland