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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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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. |
format | Online Article Text |
id | pubmed-7063260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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