IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-22196-y.html
   My bibliography  Save this article

miR-135a-5p mediates memory and synaptic impairments via the Rock2/Adducin1 signaling pathway in a mouse model of Alzheimer’s disease

Author

Listed:
  • Kai Zheng

    (Huazhong University of Science and Technology)

  • Fan Hu

    (Huazhong University of Science and Technology)

  • Yang Zhou

    (Huazhong University of Science and Technology)

  • Juan Zhang

    (Huazhong University of Science and Technology)

  • Jie Zheng

    (Huazhong University of Science and Technology)

  • Chuan Lai

    (Huazhong University of Science and Technology)

  • Wan Xiong

    (Huazhong University of Science and Technology)

  • Ke Cui

    (Huazhong University of Science and Technology)

  • Ya-Zhuo Hu

    (Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatric Disease, Institute of Geriatrics, Chinese PLA General Hospital and Chinese PLA Medical Academy)

  • Zhi-Tao Han

    (Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatric Disease, Institute of Geriatrics, Chinese PLA General Hospital and Chinese PLA Medical Academy)

  • Hong-Hong Zhang

    (Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatric Disease, Institute of Geriatrics, Chinese PLA General Hospital and Chinese PLA Medical Academy)

  • Jian-Guo Chen

    (Huazhong University of Science and Technology)

  • Heng-Ye Man

    (Boston University)

  • Dan Liu

    (Huazhong University of Science and Technology)

  • Youming Lu

    (Huazhong University of Science and Technology)

  • Ling-Qiang Zhu

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

Abstract

Aberrant regulation of microRNAs (miRNAs) has been implicated in the pathogenesis of Alzheimer’s disease (AD), but most abnormally expressed miRNAs found in AD are not regulated by synaptic activity. Here we report that dysfunction of miR-135a-5p/Rock2/Add1 results in memory/synaptic disorder in a mouse model of AD. miR-135a-5p levels are significantly reduced in excitatory hippocampal neurons of AD model mice. This decrease is tau dependent and mediated by Foxd3. Inhibition of miR-135a-5p leads to synaptic disorder and memory impairments. Furthermore, excess Rock2 levels caused by loss of miR-135a-5p plays an important role in the synaptic disorder of AD via phosphorylation of Ser726 on adducin 1 (Add1). Blocking the phosphorylation of Ser726 on Add1 with a membrane-permeable peptide effectively rescues the memory impairments in AD mice. Taken together, these findings demonstrate that synaptic-related miR-135a-5p mediates synaptic/memory deficits in AD via the Rock2/Add1 signaling pathway, illuminating a potential therapeutic strategy for AD.

Suggested Citation

  • Kai Zheng & Fan Hu & Yang Zhou & Juan Zhang & Jie Zheng & Chuan Lai & Wan Xiong & Ke Cui & Ya-Zhuo Hu & Zhi-Tao Han & Hong-Hong Zhang & Jian-Guo Chen & Heng-Ye Man & Dan Liu & Youming Lu & Ling-Qiang , 2021. "miR-135a-5p mediates memory and synaptic impairments via the Rock2/Adducin1 signaling pathway in a mouse model of Alzheimer’s disease," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22196-y
    DOI: 10.1038/s41467-021-22196-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-22196-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-22196-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22196-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.