Drug repurposing screens identify compounds that inhibit α-synuclein oligomers' membrane disruption and block antibody interactions

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Drug repurposing screens identify compounds that inhibit α-synuclein oligomers' membrane disruption and block antibody interactions

Chemical Science 2023
Arun Kumar Somavarapu, Giulia Kleijwegt, Madhu Nagaraj, Parvez Alam, Janni Nielsena and Daniel E. Otzen

This study used drug-repurposing screens to find small molecules that block the toxic activity of α-synuclein oligomers (αSOs), a membrane-disrupting species implicated in Parkinson's disease; screening 2000+ compounds against αSO-induced liposome permeabilization yielded seven leads. Flow Induced Dispersion Analysis (FIDA), on a Fida 1 instrument, measured the hydrodynamic radius of fluorescently labeled αSOs in solution to determine their binding affinity (apparent Kd) for anionic DOPG liposomes and four candidate neuronal proteins, and to confirm that top leads inhibit αSO–liposome binding. It is an example of using FIDA to measure oligomer binding affinity and screen inhibitors in solution.

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Drug repurposing screens identify compounds that inhibit α-synuclein oligomers' membrane disruption and block antibody interactions
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