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

ABSTRACT: Small soluble oligomers of the protein α-synuclein (αSO) have been linked to disruptions in neuronal homeostasis, contributing to the development of Parkinson's Disease (PD). While this makes αSO an obvious drug target, the development of effective therapeutics against αSO is challenged by its low abundance and structural and morphological complexity. Here, we employ two different approaches to neutralize toxic interactions made by αSOs with different cellular components. First, we use available data to identify four neuronal proteins as likely candidates for αSO interactions, namely Cfl1, Uchl1, Sirt2 and SerRS. However, despite promising results when immobilized, all 4 proteins only bind weakly to αSO in solution in microfluidic assays, making them inappropriate for screening. In contras

SUBMITTER: Somavarapu AK 

PROVIDER: S-EPMC10016340 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature