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Small molecule inhibitors of α-synuclein oligomers identified by targeting early dopamine-mediated motor impairment in C. elegans.

Kevin S ChenKrystal MenezesJarlath B RodgersDarren M O'HaraNhat TranKazuko FujisawaSeiya IshikuraShahin KhodaeiHien ChauAnna CranstonMinesh KapadiaGrishma PawarSusan PingAldis KrizusAlix LacosteScott SpanglerNaomi P VisanjiConnie MarrasNour K MajbourOmar M A El-AgnafAndres M LozanoJoseph CulottiSatoshi SuoWilliam S RyuSuneil K KaliaLorraine V Kalia
Published in: Molecular neurodegeneration (2021)
We identified a C. elegans locomotor abnormality due to dopaminergic neuron dysfunction that models early α-synuclein-mediated neurodegeneration. Our innovative approach applying this in vivo model to a multi-step drug repurposing screen, with artificial intelligence-driven in silico and in vitro methods, resulted in the discovery of at least one drug that may be repurposed as a disease-modifying therapy for Parkinson's disease.
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