ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Identification of 12/15-lipoxygenase as a regulator of axon degeneration through high-content screening.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- Article
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- Autosomal-dominant macular dystrophy linked to a chromosome 17 tandem duplication.JCI insight · 2024Article
- Tempol, a Superoxide Dismutase Mimetic, Inhibits Wallerian Degeneration Following Spinal Cord Injury by Preventing Glutathione Depletion and Aldose Reductase Activation.Journal of neurotrauma · 2024Article
- Molsidomine provides neuroprotection against vincristine-induced peripheral neurotoxicity through soluble guanylyl cyclase activation.Scientific reports · 2024Article
- Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes.Cell & bioscience · 2023Article
- Modeling chemotherapy induced peripheral neuropathy (CIPN) in vitro: Prospects and limitations.Experimental neurology · 2020Review
- Cell death assays for neurodegenerative disease drug discovery.Expert opinion on drug discovery · 2019Review
- The Ste20 Family Kinases MAP4K4, MINK1, and TNIK Converge to Regulate Stress-Induced JNK Signaling in Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Review
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Axon degeneration is a programed process that takes place during development, in response to neuronal injury, and as a component of neurodegenerative disease pathology, yet the molecular mechanisms that drive this process remain poorly defined. In this study, we have developed a semi-automated, 384-well format axon degeneration assay in rat dorsal root ganglion (DRG) neurons using a trophic factor withdrawal paradigm. Using this setup, we have screened a library of known drugs and bioactives to identify several previously unappreciated regulators of axon degeneration, including lipoxygenases. Multiple structurally distinct lipoxygenase inhibitors as well as mouse DRG neurons lacking expression of 12/15-lipoxygenase display protection of axons in this context. Retinal ganglion cell axons from 12/15-lipoxygenase-null mice were similarly protected from degeneration following nerve crush injury. Through additional mechanistic studies, we demonstrate that lipoxygenases act cell autonomously within neurons to regulate degeneration, and are required for mitochondrial permeabilization and caspase activation in the axon. These findings suggest that these enzymes may represent an attractive target for treatment of neuropathies and provide a potential mechanism for the neuroprotection observed in various settings following lipoxygenase inhibitor treatment.
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