TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau

Maxime W C Rousseaux, Maria de Haro, Cristian A. Lasagna-Reeves, Antonia de Maio, Jeehye Park, Paymaan Jafar-Nejad, Ismael Al-Ramahi, Ajay Sharma, Lauren See, Nan Lu, Luis Vilanova-Velez, Tiemo J. Klisch, Thomas F. Westbrook, Juan C Troncoso, Juan Botas, Huda Y. Zoghbi

Research output: Contribution to journalArticle

Abstract

Several neurodegenerative diseases are driven by the toxic gain-of-function of specific proteins within the brain. Elevated levels of alpha-synuclein (α-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 α -Syn and tau overlap pathologically. The connections between α -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 α -Syn and tau. We found that TRIM28 regulates α -Syn and tau levels and that its reduction rescues toxicity in animal models of tau- and α -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.

Original languageEnglish (US)
Article numbere19809
JournaleLife
Volume5
Issue numberOCTOBER2016
DOIs
StatePublished - Oct 25 2016

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alpha-Synuclein
Toxicity
Parkinson Disease
Alzheimer Disease
Proteins
Poisons
Neurodegenerative diseases
Neurodegenerative Diseases
Animal Models
Brain
Animals
Genes
Therapeutics

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Rousseaux, M. W. C., de Haro, M., Lasagna-Reeves, C. A., de Maio, A., Park, J., Jafar-Nejad, P., ... Zoghbi, H. Y. (2016). TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau. eLife, 5(OCTOBER2016), [e19809]. https://doi.org/10.7554/eLife.19809

TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau. / Rousseaux, Maxime W C; de Haro, Maria; Lasagna-Reeves, Cristian A.; de Maio, Antonia; Park, Jeehye; Jafar-Nejad, Paymaan; Al-Ramahi, Ismael; Sharma, Ajay; See, Lauren; Lu, Nan; Vilanova-Velez, Luis; Klisch, Tiemo J.; Westbrook, Thomas F.; Troncoso, Juan C; Botas, Juan; Zoghbi, Huda Y.

In: eLife, Vol. 5, No. OCTOBER2016, e19809, 25.10.2016.

Research output: Contribution to journalArticle

Rousseaux, MWC, de Haro, M, Lasagna-Reeves, CA, de Maio, A, Park, J, Jafar-Nejad, P, Al-Ramahi, I, Sharma, A, See, L, Lu, N, Vilanova-Velez, L, Klisch, TJ, Westbrook, TF, Troncoso, JC, Botas, J & Zoghbi, HY 2016, 'TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau', eLife, vol. 5, no. OCTOBER2016, e19809. https://doi.org/10.7554/eLife.19809
Rousseaux MWC, de Haro M, Lasagna-Reeves CA, de Maio A, Park J, Jafar-Nejad P et al. TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau. eLife. 2016 Oct 25;5(OCTOBER2016). e19809. https://doi.org/10.7554/eLife.19809
Rousseaux, Maxime W C ; de Haro, Maria ; Lasagna-Reeves, Cristian A. ; de Maio, Antonia ; Park, Jeehye ; Jafar-Nejad, Paymaan ; Al-Ramahi, Ismael ; Sharma, Ajay ; See, Lauren ; Lu, Nan ; Vilanova-Velez, Luis ; Klisch, Tiemo J. ; Westbrook, Thomas F. ; Troncoso, Juan C ; Botas, Juan ; Zoghbi, Huda Y. / TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau. In: eLife. 2016 ; Vol. 5, No. OCTOBER2016.
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