Send to

Choose Destination
Elife. 2018 Jun 4;7. pii: e36768. doi: 10.7554/eLife.36768.

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

Author information

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, United States.
Program in Developmental Biology, Baylor College of Medicine, Houston, United States.
Medical Scientist Training Program, Baylor College of Medicine, Houston, United States.
Department of Neuroscience, Baylor College of Medicine, Houston, United States.
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States.


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 (<xref ref-type="bibr" rid="bib21">Rousseaux et al., 2016</xref>). However, it was not clear how TRIM28 regulates 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.


Alzheimer's disease; Parkinson's disease; Tau; alpha-Synuclein; dosage sensitivity; human; mouse; neuroscience; safety

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center