Depleting Trim28 in adult mice is well tolerated and reduces levels of α-synuclein and tau
- Baylor College of Medicine, United States
- Texas Children's Hospital, United States
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.
Data availability
No datasets were generated in this study. All data are presented in this manuscript.
Article and author information
Author details
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.
Reviewing Editor
- Susan L Ackerman, Howard Hughes Medical Institute, University of California, San Diego, United States
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.
Version history
- Received: March 19, 2018
- Accepted: June 3, 2018
- Accepted Manuscript published: June 4, 2018 (version 1)
- 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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Depleting Trim28 in adult mice is well tolerated and reduces levels of α-synuclein and tau
eLife 7:e36768.
https://doi.org/10.7554/eLife.36768
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