1. Assays to measure small molecule Hsp70 agonist activity in vitro and in vivo.
- Author
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Shapiro O, Woods C, Gleixner AM, Sannino S, Ngo M, McDaniels MD, Wipf P, Hukriede NA, Donnelly CJ, and Brodsky JL
- Subjects
- Animals, Humans, Small Molecule Libraries pharmacology, Small Molecule Libraries chemistry, Optogenetics methods, DNA-Binding Proteins agonists, DNA-Binding Proteins metabolism, HSP70 Heat-Shock Proteins metabolism, HSP70 Heat-Shock Proteins agonists, Zebrafish
- Abstract
Hsp70 prevents protein aggregation and is cytoprotective, but sustained Hsp70 overexpression is problematic. Therefore, we characterized small molecule agonists that augment Hsp70 activity. Because cumbersome assays were required to assay agonists, we developed cell-based and in vivo assays in which disease-associated consequences of Hsp70 activation can be quantified. One assay uses an optogenetic system in which the formation of TDP-43 inclusions can be controlled, and the second assay employs a zebrafish model for acute kidney injury (AKI). These complementary assays will facilitate future work to identify new Hsp70 agonists as well as optimized agonist derivatives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2025
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