IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms6244.html
   My bibliography  Save this article

Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo

Author

Listed:
  • Phillip M. Rappold

    (Center for Translational Neuromedicine, University of Rochester School of Medicine)

  • Mei Cui

    (Center for Translational Neuromedicine, University of Rochester School of Medicine
    Present address: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China)

  • Jonathan C. Grima

    (Center for Translational Neuromedicine, University of Rochester School of Medicine
    Present address: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA)

  • Rebecca Z. Fan

    (Plymouth University)

  • Karen L. de Mesy-Bentley

    (University of Rochester Medical Center)

  • Linan Chen

    (University of Chicago)

  • Xiaoxi Zhuang

    (University of Chicago)

  • William J. Bowers

    (Center for Neural Development and Disease, University of Rochester Medical Center
    Present address: Office of Research and Sponsored Programs, SUNY Oswego, 7060 Route 104, Oswego, New York 13126, USA)

  • Kim Tieu

    (Center for Translational Neuromedicine, University of Rochester School of Medicine
    Plymouth University)

Abstract

Mitochondrial dysfunction has been reported in both familial and sporadic Parkinson’s disease (PD). However, effective therapy targeting this pathway is currently inadequate. Recent studies suggest that manipulating the processes of mitochondrial fission and fusion has considerable potential for treating human diseases. To determine the therapeutic impact of targeting these pathways on PD, we used two complementary mouse models of mitochondrial impairments as seen in PD. We show here that blocking mitochondrial fission is neuroprotective in the PTEN-induced putative kinase-1 deletion (PINK1−/−) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse models. Specifically, we show that inhibition of the mitochondrial fission GTPase dynamin-related protein-1 (Drp1) using gene-based and small-molecule approaches attenuates neurotoxicity and restores pre-existing striatal dopamine release deficits in these animal models. These results suggest Drp1 inhibition as a potential treatment for PD.

Suggested Citation

  • Phillip M. Rappold & Mei Cui & Jonathan C. Grima & Rebecca Z. Fan & Karen L. de Mesy-Bentley & Linan Chen & Xiaoxi Zhuang & William J. Bowers & Kim Tieu, 2014. "Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6244
    DOI: 10.1038/ncomms6244
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms6244
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms6244?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:5:y:2014:i:1:d:10.1038_ncomms6244. 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.