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

ABSTRACT: 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.

SUBMITTER: Varkuti BH

PROVIDER: S-EPMC7063260 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Varkuti Boglarka H BH Liu Ze Z Kepiro Miklos M Pacifico Rodrigo R Gai Yunchao Y Kamenecka Ted T Davis Ronald L RL

iScience 20200222 3

We developed a high-throughput assay for modulators of mitochondrial function in neurons measuring inner mitochondrial membrane potential (ΔΨ<sub>m</sub>) 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 com ...[more]

PMID: 32146326

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