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

作者：Rousseaux Maxime W C; Revelli Jean Pierre; Vazquez Velez Gabriel E; Kim Ji Yoen; Craigen Evelyn; Gonzales Kristyn; Beckinghausen Jaclyn; Zoghbi Huda Y^*

来源：eLife, 2018, 7: e36768.

DOI：10.7554/eLife.36768.001

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 asynuclein (alpha-Syn). Previously we found that TRIM28 regulates the levels and toxicity of alpha-Syn and tau (Rousseaux et at, 2016). However, it was not clear how TRIM28 regulates alpha-Syn and it was not known if its chronic inhibition later in life was safe. Here, we show that TRIM28 may regulate alpha-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 alpha-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 alpha-Syn and tau levels.

• 出版日期2018-6-4