IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms4496.html
   My bibliography  Save this article

Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52

Author

Listed:
  • Chulman Jo

    (University of Rochester Medical Center, University of Rochester, 601 Elmwood Avenue
    Present address: Division of Brain Diseases, Center for Biomedical Science, Korea National Institute of Health, Chungcheongbuk-do 363-951, Korea)

  • Soner Gundemir

    (University of Rochester Medical Center, University of Rochester, 601 Elmwood Avenue)

  • Susanne Pritchard

    (University of Rochester Medical Center, University of Rochester, 601 Elmwood Avenue)

  • Youngnam N. Jin

    (University of Rochester Medical Center, University of Rochester, 601 Elmwood Avenue)

  • Irfan Rahman

    (Lung Biology and Disease Program, University of Rochester Medical Center, University of Rochester, 601 Elmwood Avenue)

  • Gail V. W. Johnson

    (University of Rochester Medical Center, University of Rochester, 601 Elmwood Avenue)

Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription factor in the defence against oxidative stress. Here we provide evidence that activation of the Nrf2 pathway reduces the levels of phosphorylated tau by induction of an autophagy adaptor protein NDP52 (also known as CALCOCO2) in neurons. The expression of NDP52, which we show has three antioxidant response elements (AREs) in its promoter region, is strongly induced by Nrf2, and its overexpression facilitates clearance of phosphorylated tau in the presence of an autophagy stimulator. In Nrf2-knockout mice, phosphorylated and sarkosyl-insoluble tau accumulates in the brains concurrent with decreased levels of NDP52. Moreover, NDP52 associates with phosphorylated tau from brain cortical samples of Alzheimer disease cases, and the amount of phosphorylated tau in sarkosyl-insoluble fractions is inversely proportional to that of NDP52. These results suggest that NDP52 plays a key role in autophagy-mediated degradation of phosphorylated tau in vivo.

Suggested Citation

  • Chulman Jo & Soner Gundemir & Susanne Pritchard & Youngnam N. Jin & Irfan Rahman & Gail V. W. Johnson, 2014. "Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52," Nature Communications, Nature, vol. 5(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4496
    DOI: 10.1038/ncomms4496
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms4496
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms4496?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. Kihyoun Park & Hyejin Lim & Jinyoung Kim & Yeseong Hwang & Yu Seol Lee & Soo Han Bae & Hyeongseok Kim & Hail Kim & Shin-Wook Kang & Joo Young Kim & Myung-Shik Lee, 2022. "Lysosomal Ca2+-mediated TFEB activation modulates mitophagy and functional adaptation of pancreatic β-cells to metabolic stress," 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:5:y:2014:i:1:d:10.1038_ncomms4496. 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.