Defining a small-molecule stimulator of the human Hsp70-disaggregase system with selectivity for DnaJB proteins
Edward Chuang,
Ryan R. Cupo,
Jeffrey R. Bevan
et al.
Abstract:Hsp70, Hsp40, and Hsp110 form a human protein-disaggregase system that solubilizes and reactivates proteins trapped in aggregated states. However, this system fails to maintain proteostasis in fatal neurodegenerative diseases. Here, we potentiate the human Hsp70-disaggregase system pharmacologically. By scouring a collection of dihydropyrimidines, we disambiguate a small molecule that specifically stimulates the Hsp70-disaggregase system against disordered aggregates and α-synuclein fibrils. The newly identifi… Show more
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