Objective/Rationale:
A central hypothesis for Parkinson’s pathology is that excessive alpha-Synuclein protein, most likely in the form of aggregates, is toxic to midbrain dopamine neurons. Our prior studies showed that mice deficient in alpha-Synuclein harbor only minor deficits, and thus reduction of alpha-synuclein accumulation may be a safe and effective approach to treatment. We have identified a novel regulatory mechanism for alpha-synuclein protein expression, based on short noncoding RNA molecules termed miRNAs.
Project Description:
We will investigate whether these miRNAs are effective in reducing alpha-synuclein, and attempt to identify therapeutics that take advantage of this pathway. First, we will identify miRNAs that can effectively regulate alpha-synuclein. Second, we will search for drug-like compounds that are able to regulate alpha-synuclein through this pathway.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
miRNAs that we identify in the first aim, and drugs in the second aim, are candidates as novel therapies for PD.
Anticipated Outcome:
We hope to identify novel mechanisms that regulate alpha-synuclein production. These represent novel therapeutics approaches for PD.
Final Outcome
Dr. Abeliovich identified several miRNA candidates that can modulate alpha-synuclein expression. He is now working to validate their potential for therapeutic relevance in midbrain cultures. Additionally, Dr. Abeliovich is continuing to complete screening in an NINDS drug library for drugs that effectively target the relevant sequence of alpha-synuclein.