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

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

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Bibliographic Details
Main Authors: Boglarka H. Varkuti, Ze Liu, Miklos Kepiro, Rodrigo Pacifico, Yunchao Gai, Ted Kameneka, Ronald L. Davis
Format: Article
Language:English
Published: Elsevier 2020-03-01
Series:iScience
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004220301152
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Summary:Summary: We developed a high-throughput assay for modulators of mitochondrial function in neurons measuring inner mitochondrial membrane potential (ΔΨm) 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. : Chemistry; Biochemistry; Molecular Neuroscience Subject Areas: Chemistry, Biochemistry, Molecular Neuroscience
ISSN:2589-0042