High-Throughput Small Molecule Screen Identifies Modulators of Mitochondrial Function in Neurons
| Autor: | Ze Liu, Miklós Képiró, Ronald L. Davis, Boglárka H. Várkuti, Theodore M. Kamenecka, Yunchao Gai, Rodrigo Pacifico |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adrenergic receptor 02 engineering and technology Molecular neuroscience 01 natural sciences Biochemistry Article 03 medical and health sciences chemistry.chemical_compound medicine lcsh:Science Neurotransmitter Inner mitochondrial membrane 030304 developmental biology 0303 health sciences Multidisciplinary Effector Correction 021001 nanoscience & nanotechnology medicine.disease Small molecule 0104 chemical sciences 3. Good health Cell biology 010404 medicinal & biomolecular chemistry Chemistry 030104 developmental biology chemistry lcsh:Q Alzheimer's disease Molecular Neuroscience 0210 nano-technology Function (biology) |
| Zdroj: | iScience iScience, Vol 23, Iss 8, Pp 101364-(2020) iScience, Vol 23, Iss 3, Pp-(2020) |
| ISSN: | 2589-0042 |
| Popis: | 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. Graphical Abstract Highlights • Dozens of small molecules identified that enhance neuronal mitochondrial function • The small molecules promote mitochondrial health and enhance oxygen consumption • They protect neurons from toxic insults associated with neurodegenerative diseases Chemistry; Biochemistry; Molecular Neuroscience |
| Databáze: | OpenAIRE |
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