摘要:SummaryWe 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 AbstractDisplay OmittedHighlights•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 diseasesChemistry; Biochemistry; Molecular Neuroscience