ArticleChemical biology & drug design2014
High-throughput screen of natural product extracts in a yeast model of polyglutamine proteotoxicity.
Article in Chemical biology & drug design, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Non-Mammalian Models for Mitochondria Research in CNS Disorders.Biomolecules · 2026Review
- From Yeast to Therapeutics: Modeling Neurodegenerative Diseases in Saccharomyces cerevisiae.Yeast (Chichester, England) · 2025Review
- A clinical study and future prospects for bioactive compounds and semi-synthetic molecules in the therapies for Huntington's disease.Molecular neurobiology · 2024Review
- The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington's Disease.Current neuropharmacology · 2023Review
- Creating and screening natural product libraries.Natural product reports · 2020Review
- Isolation and Identification of a Novel Anti-protein Aggregation Activity of Lignin-Carbohydrate Complex FromFrontiers in bioengineering and biotechnology · 2020Article
- Yeast Models for Amyloids and Prions: Environmental Modulation and Drug Discovery.Molecules (Basel, Switzerland) · 2019Review
- Yeast Models for the Study of Amyloid-Associated Disorders and Development of Future Therapy.Frontiers in molecular biosciences · 2019Review
- Studying Huntington's Disease in Yeast: From Mechanisms to Pharmacological Approaches.Frontiers in molecular neuroscience · 2018Review
- Microscale Adaptation of In Vitro Transcription/Translation for High-Throughput Screening of Natural Product Extract Libraries.Chemical biology & drug design · 2015Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Proteins with expanded polyglutamine (polyQ) segments cause a number of fatal neurodegenerative disorders, including Huntington's disease (HD). Previous high-throughput screens in cellular and biochemical models of HD have revealed compounds that mitigate polyQ aggregation and proteotoxicity, providing insight into the mechanisms of disease and leads for potential therapeutics. However, the structural diversity of natural products has not yet been fully mobilized toward these goals. Here, we have screened a collection of ~11 000 natural product extracts for the ability to recover the slow growth of ΔProQ103-expressing yeast cells in 384-well plates (Z' ~ 0.7, CV ~ 8%). This screen identified actinomycin D as a strong inhibitor of polyQ aggregation and proteotoxicity at nanomolar concentrations (~50-500 ng/mL). We found that a low dose of actinomycin D increased the levels of the heat-shock proteins Hsp104, Hsp70 and Hsp26 and enhanced binding of Hsp70 to the polyQ in yeast. Actinomycin also suppressed aggregation of polyQ in mammalian cells, suggesting a conserved mechanism. These results establish natural products as a rich source of compounds with interesting mechanisms of action against polyQ disorders.
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Registered trials
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