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A Novel Assay to Identify Antagonists of a-Synuclein Assembly in the Cellular Milieu

The aggregation of α-Synuclein (αS), a neuronal protein in the central nervous system, is a pathological hallmark of many synucleinopathies, including Parkinson’s disease (PD). Synucleinopathies are neurodegenerative diseases caused by the aggregation of the protein αS. There is a pressing need to identify strategies to cure or alleviate the symptoms of PD. Our approach to this problem is to identify ligands that can inhibit the process of αS aggregation. We are developing a novel assay to test the ability of ligands to inhibit aggregation of α-Synuclein (αS) and rescue cell toxicity mediated by αS. We have currently used an in-house antagonist of αS aggregation, identified as SK-129.We have demonstrated that cells treated with the αS protein plus the SK-129 molecule have significantly fewer aggregates of αS and rescued cell viability. This assay will be utilized to screen large libraries of ligands (in-house and commercially available) to identify potent antagonists of αS aggregation. In tandem, we will assess the ability of molecules to inhibit αS aggregation and rescue αS mediated cytotoxicity in a high throughput manner. This assay will aid in expediting the process of identifying potential therapeutics for the treatment of PD.