AI Article Synopsis

  • Alzheimer's and Parkinson's diseases involve harmful proteins like tau and α-synuclein, requiring long-term treatments to manage their effects.
  • Research has indicated that TRIM28 plays a role in controlling the levels and toxicity of these proteins, but its mechanisms and safety of long-term inhibition were unclear.
  • The study found that reducing TRIM28 in adult mice does not cause negative behavioral or health issues and actually lowers the levels of α-Syn and tau, suggesting that inhibiting TRIM28 in adults could be a promising strategy to manage these neurodegenerative diseases.

Article 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 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993537PMC
http://dx.doi.org/10.7554/eLife.36768DOI Listing

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