| First Author | Rousseaux MW | Year | 2016 |
| Journal | Elife | Volume | 5 |
| PubMed ID | 27779468 | Mgi Jnum | J:238738 |
| Mgi Id | MGI:5823529 | Doi | 10.7554/eLife.19809 |
| Citation | Rousseaux MW, et al. (2016) TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau. Elife 5:e19809 |
| abstractText | Several neurodegenerative diseases are driven by the toxic gain-of-function of specific proteins within the brain. Elevated levels of alpha-synuclein (alpha-Syn) appear to drive neurotoxicity in Parkinson's disease (PD); neuronal accumulation of tau is a hallmark of Alzheimer's disease (AD); and their increased levels cause neurodegeneration in humans and model organisms. Despite the clinical differences between AD and PD, several lines of evidence suggest that alpha-Syn and tau overlap pathologically. The connections between alpha-Syn and tau led us to ask whether these proteins might be regulated through a shared pathway. We therefore screened for genes that affect post-translational levels of alpha-Syn and tau. We found that TRIM28 regulates alpha-Syn and tau levels and that its reduction rescues toxicity in animal models of tau- and alpha-Syn-mediated degeneration. TRIM28 stabilizes and promotes the nuclear accumulation and toxicity of both proteins. Intersecting screens across comorbid proteinopathies thus reveal shared mechanisms and therapeutic entry points. |
