Abstract
Axon degeneration underlies many common neurological disorders, but the signaling pathways that orchestrate axon degeneration are unknown. We found that dual leucine kinase (DLK) [corrected to add (DLK) abbreviation] promoted degeneration of severed axons in Drosophila and mice, and that its target, c-Jun N-terminal kinase, promoted degeneration locally in axons as they committed to degenerate. This pathway also promoted degeneration after chemotherapy exposure and may be a component of a general axon self-destruction program.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Anthracenes / pharmacology
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Axons / metabolism
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Axons / pathology*
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Axons / ultrastructure
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Axotomy / methods
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Cells, Cultured
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Disease Models, Animal
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Drosophila
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Embryo, Mammalian
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Enzyme Inhibitors / pharmacology
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Ganglia, Spinal / cytology
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Green Fluorescent Proteins / genetics
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JNK Mitogen-Activated Protein Kinases / genetics
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JNK Mitogen-Activated Protein Kinases / metabolism*
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MAP Kinase Kinase Kinases / metabolism*
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Mice
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Mice, Inbred C57BL
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Nerve Tissue Proteins / genetics
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Neurons / drug effects
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Neurons / metabolism
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Neurons / pathology*
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Neurons / ultrastructure
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Olfactory Receptor Neurons / pathology
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Sciatic Nerve / injuries
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Sciatic Nerve / pathology
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Wallerian Degeneration / genetics
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Wallerian Degeneration / pathology*
Substances
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Anthracenes
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Enzyme Inhibitors
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Nerve Tissue Proteins
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Green Fluorescent Proteins
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pyrazolanthrone
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinases
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mitogen-activated protein kinase kinase kinase 12