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Depleting Trim28 in adult mice is well tolerated and reduces levels of α-synuclein and tau

  1. Maxime WC Rousseaux
  2. Jean-Pierre Revelli
  3. Gabriel E Vázquez-Vélez
  4. Ji-Yoen Kim
  5. Evelyn Craigen
  6. Kristyn Gonzales
  7. Jaclyn Beckinghausen
  8. Huda Y Zoghbi  Is a corresponding author
  1. Baylor College of Medicine, United States
  2. Texas Children's Hospital, United States
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Cite this article as: eLife 2018;7:e36768 doi: 10.7554/eLife.36768

Abstract

Alzheimer's and Parkinson's disease are late onset neurodegenerative diseases that will require therapy over decades to mitigate the effects of disease-driving proteins such tau and α-synuclein (α-Syn). Previously we found that TRIM28 regulates the levels and toxicity of α-Syn and tau (Rousseaux et al., 2016). However, it was not clear how TRIM28 regulate α-Syn and it was not known if its chronic inhibition later in life was safe. Here, we show that TRIM28 may regulate α-Syn and tau levels via SUMOylation, and that genetic suppression of Trim28 in adult mice is compatible with life. We were surprised to see that mice lacking Trim28 in adulthood do not exhibit behavioral or pathological phenotypes, and importantly, adult reduction of TRIM28 results in a decrease of α-Syn and tau levels. These results suggest that deleterious effects from TRIM28 depletion are limited to development and that its inhibition adulthood provides a potential path for modulating α-Syn and tau levels.

Article and author information

Author details

  1. Maxime WC Rousseaux

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  2. Jean-Pierre Revelli

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  3. Gabriel E Vázquez-Vélez

    Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
    Competing interests
    No competing interests declared.
  4. Ji-Yoen Kim

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  5. Evelyn Craigen

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  6. Kristyn Gonzales

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  7. Jaclyn Beckinghausen

    Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
    Competing interests
    No competing interests declared.
  8. Huda Y Zoghbi

    Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
    For correspondence
    hzoghbi@bcm.edu
    Competing interests
    Huda Y Zoghbi, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0700-3349

Funding

Parkinson's Foundation (PF-JFA-1762)

  • Maxime WC Rousseaux

UCB Pharma

  • Huda Y Zoghbi

Robert A. and Renee E. Belfer Family Foundation

  • Huda Y Zoghbi

The Huffington Foundation

  • Huda Y Zoghbi

The Hamill Foundation

  • Huda Y Zoghbi

Howard Hughes Medical Institute

  • Huda Y Zoghbi

Intellectual and Developmental Disabilities Research Center (NIH U54 HD083092)

  • Huda Y Zoghbi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Up to five mice were housed per cage and kept on a 12 h light; 12 h dark cycle and were given water and standard rodent chow ad libitum. All procedures carried out in mice were approved by the Institutional Animal Care and Use Committee for Baylor College of Medicine and Affiliates under protocol AN-1013.

Reviewing Editor

  1. Susan L Ackerman, Howard Hughes Medical Institute, University of California, San Diego, United States

Publication history

  1. Received: March 19, 2018
  2. Accepted: June 3, 2018
  3. Accepted Manuscript published: June 4, 2018 (version 1)
  4. Version of Record published: June 8, 2018 (version 2)

Copyright

© 2018, Rousseaux et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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