Targeted Disruption of TRIM28 to Reduce Alpha-synuclein Levels
Target Validation, 2014
We have previously performed a screen to find new pathways that may regulate alpha-synuclein, the toxic protein that accumulates in the cells of people with Parkinsonís disease (PD). Our screen identified a gene (TRIM28) that appears to regulate alpha-synuclein levels and toxicity in pre-clinical models of PD.
We will test whether targeted reduction of TRIM28 in PD models that overexpress alpha-synuclein can delay the onset of disease. Specifically, we will decrease or increase levels of TRIM28 and see its impact on alpha-synuclein levels and toxicity. We will then test whether a specific function of TRIM28 (termed SUMOylation) is key in promoting its toxicity.
Relevance to Diagnosis/Treatment of Parkinsonís Disease:
Accumulation of alpha-synuclein may be the driver of Parkinsonís disease. As such, we want to reduce its levels to hopefully delay or even halt the progression of the disease.
By understanding how TRIM28 regulates alpha-synuclein levels, we hope to better understand the mechanism through which alpha-synuclein accumulates and becomes toxic. We also think that the development of drugs that can target the SUMOylation function of TRIM28 may be a promising therapeutic avenue.
Professor at Baylor College of Medicine
Investigator at Howard Hughes Medical Institute
Location: Houston, Texas, United States
Discover More Grants
Within the Same Program
Within the Same Funding Year