IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-14353-6.html
   My bibliography  Save this article

YAP-dependent necrosis occurs in early stages of Alzheimer’s disease and regulates mouse model pathology

Author

Listed:
  • Hikari Tanaka

    (Tokyo Medical and Dental University)

  • Hidenori Homma

    (Tokyo Medical and Dental University)

  • Kyota Fujita

    (Tokyo Medical and Dental University)

  • Kanoh Kondo

    (Tokyo Medical and Dental University)

  • Shingo Yamada

    (Shino-Test Corporation, 2-29-14, Ohino-dai, Minami-ku)

  • Xiaocen Jin

    (Tokyo Medical and Dental University)

  • Masaaki Waragai

    (Higashi Matsudo Municipal Hospital)

  • Gaku Ohtomo

    (The University of Tokyo, Graduate School of Medicine)

  • Atsushi Iwata

    (The University of Tokyo, Graduate School of Medicine)

  • Kazuhiko Tagawa

    (Tokyo Medical and Dental University)

  • Naoki Atsuta

    (Brain and Mind Research Center, Nagoya University Graduate School of Medicine)

  • Masahisa Katsuno

    (Brain and Mind Research Center, Nagoya University Graduate School of Medicine)

  • Naoki Tomita

    (Tohoku University)

  • Katsutoshi Furukawa

    (Tohoku University)

  • Yuko Saito

    (National Center of Neurology and Psychiatry)

  • Takashi Saito

    (RIKEN Center for Brain Science)

  • Ayaka Ichise

    (Keio University School of Medicine)

  • Shinsuke Shibata

    (Keio University School of Medicine)

  • Hiroyuki Arai

    (Tohoku University)

  • Takaomi Saido

    (RIKEN Center for Brain Science)

  • Marius Sudol

    (National University of Singapore, Yong Loo Li School of Medicine)

  • Shin-ichi Muramatsu

    (Jichi Medical University)

  • Hideyuki Okano

    (Keio University School of Medicine)

  • Elliott J. Mufson

    (Barrow Neurological Institute)

  • Gen Sobue

    (Brain and Mind Research Center, Nagoya University Graduate School of Medicine)

  • Shigeo Murayama

    (Brain Bank for Aging Research, Tokyo Metropolitan Institute of Gerontology)

  • Hitoshi Okazawa

    (Tokyo Medical and Dental University)

Abstract

The timing and characteristics of neuronal death in Alzheimer’s disease (AD) remain largely unknown. Here we examine AD mouse models with an original marker, myristoylated alanine-rich C-kinase substrate phosphorylated at serine 46 (pSer46-MARCKS), and reveal an increase of neuronal necrosis during pre-symptomatic phase and a subsequent decrease during symptomatic phase. Postmortem brains of mild cognitive impairment (MCI) rather than symptomatic AD patients reveal a remarkable increase of necrosis. In vivo imaging reveals instability of endoplasmic reticulum (ER) in mouse AD models and genome-edited human AD iPS cell-derived neurons. The level of nuclear Yes-associated protein (YAP) is remarkably decreased in such neurons under AD pathology due to the sequestration into cytoplasmic amyloid beta (Aβ) aggregates, supporting the feature of YAP-dependent necrosis. Suppression of early-stage neuronal death by AAV-YAPdeltaC reduces the later-stage extracellular Aβ burden and cognitive impairment, suggesting that preclinical/prodromal YAP-dependent neuronal necrosis represents a target for AD therapeutics.

Suggested Citation

  • Hikari Tanaka & Hidenori Homma & Kyota Fujita & Kanoh Kondo & Shingo Yamada & Xiaocen Jin & Masaaki Waragai & Gaku Ohtomo & Atsushi Iwata & Kazuhiko Tagawa & Naoki Atsuta & Masahisa Katsuno & Naoki To, 2020. "YAP-dependent necrosis occurs in early stages of Alzheimer’s disease and regulates mouse model pathology," Nature Communications, Nature, vol. 11(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14353-6
    DOI: 10.1038/s41467-020-14353-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-14353-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-14353-6?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Xiaocen Jin & Hikari Tanaka & Meihua Jin & Kyota Fujita & Hidenori Homma & Maiko Inotsume & Huang Yong & Kenichi Umeda & Noriyuki Kodera & Toshio Ando & Hitoshi Okazawa, 2023. "PQBP5/NOL10 maintains and anchors the nucleolus under physiological and osmotic stress conditions," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Takashi Nagashima & Suguru Tohyama & Kaori Mikami & Masashi Nagase & Mieko Morishima & Atsushi Kasai & Hitoshi Hashimoto & Ayako M. Watabe, 2022. "Parabrachial-to-parasubthalamic nucleus pathway mediates fear-induced suppression of feeding in male mice," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

    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:11:y:2020:i:1:d:10.1038_s41467-020-14353-6. 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.