Objective/Rationale:
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 Parkinson’s disease (PD). Our screen identified a gene (TRIM28) that appears to regulate alpha-synuclein levels and toxicity in pre-clinical models of PD.
Project Description:
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 Parkinson’s Disease:
Accumulation of alpha-synuclein may be the driver of Parkinson’s disease. As such, we want to reduce its levels to hopefully delay or even halt the progression of the disease.
Anticipated Outcome:
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.