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High-Throughput Small Molecule Screen Identifies Modulators of Mitochondrial Function in Neurons

We developed a high-throughput assay for modulators of mitochondrial function in neurons measuring inner mitochondrial membrane potential (ΔΨ(m)) and ATP production. The assay was used to screen a library of small molecules, which led to the identification of structural/functional classes of mitocho...

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Detalles Bibliográficos
Autores principales: Varkuti, Boglarka H., Liu, Ze, Kepiro, Miklos, Pacifico, Rodrigo, Gai, Yunchao, Kameneka, Ted, Davis, Ronald L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063260/
https://www.ncbi.nlm.nih.gov/pubmed/32146326
http://dx.doi.org/10.1016/j.isci.2020.100931
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author Varkuti, Boglarka H.
Liu, Ze
Kepiro, Miklos
Pacifico, Rodrigo
Gai, Yunchao
Kameneka, Ted
Davis, Ronald L.
author_facet Varkuti, Boglarka H.
Liu, Ze
Kepiro, Miklos
Pacifico, Rodrigo
Gai, Yunchao
Kameneka, Ted
Davis, Ronald L.
author_sort Varkuti, Boglarka H.
collection PubMed
description We developed a high-throughput assay for modulators of mitochondrial function in neurons measuring inner mitochondrial membrane potential (ΔΨ(m)) and ATP production. The assay was used to screen a library of small molecules, which led to the identification of structural/functional classes of mitochondrial modulators such as local anesthetics, isoflavones, COXII inhibitors, adrenergic receptor blockers, and neurotransmitter system effectors. Our results show that some of the isolated compounds promote mitochondrial health, enhance oxygen consumption rate, and protect neurons against toxic insults found in the cellular environment of Alzheimer disease. These studies offer a set of compounds that may provide efficacy in protecting the mitochondrial system in neurodegenerative disorders.
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spelling pubmed-70632602020-03-16 High-Throughput Small Molecule Screen Identifies Modulators of Mitochondrial Function in Neurons Varkuti, Boglarka H. Liu, Ze Kepiro, Miklos Pacifico, Rodrigo Gai, Yunchao Kameneka, Ted Davis, Ronald L. iScience Article We developed a high-throughput assay for modulators of mitochondrial function in neurons measuring inner mitochondrial membrane potential (ΔΨ(m)) and ATP production. The assay was used to screen a library of small molecules, which led to the identification of structural/functional classes of mitochondrial modulators such as local anesthetics, isoflavones, COXII inhibitors, adrenergic receptor blockers, and neurotransmitter system effectors. Our results show that some of the isolated compounds promote mitochondrial health, enhance oxygen consumption rate, and protect neurons against toxic insults found in the cellular environment of Alzheimer disease. These studies offer a set of compounds that may provide efficacy in protecting the mitochondrial system in neurodegenerative disorders. Elsevier 2020-02-22 /pmc/articles/PMC7063260/ /pubmed/32146326 http://dx.doi.org/10.1016/j.isci.2020.100931 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Varkuti, Boglarka H.
Liu, Ze
Kepiro, Miklos
Pacifico, Rodrigo
Gai, Yunchao
Kameneka, Ted
Davis, Ronald L.
High-Throughput Small Molecule Screen Identifies Modulators of Mitochondrial Function in Neurons
title High-Throughput Small Molecule Screen Identifies Modulators of Mitochondrial Function in Neurons
title_full High-Throughput Small Molecule Screen Identifies Modulators of Mitochondrial Function in Neurons
title_fullStr High-Throughput Small Molecule Screen Identifies Modulators of Mitochondrial Function in Neurons
title_full_unstemmed High-Throughput Small Molecule Screen Identifies Modulators of Mitochondrial Function in Neurons
title_short High-Throughput Small Molecule Screen Identifies Modulators of Mitochondrial Function in Neurons
title_sort high-throughput small molecule screen identifies modulators of mitochondrial function in neurons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063260/
https://www.ncbi.nlm.nih.gov/pubmed/32146326
http://dx.doi.org/10.1016/j.isci.2020.100931
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