Home > Publications Database > An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury. > print

001     163651
005     20231025131157.0
024 7 _ |a 10.1016/j.neuron.2021.10.007
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024 7 _ |a 1097-4199
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037 _ _ |a DZNE-2022-00397
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100 1 _ |a Hilton, Brett J
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245 _ _ |a An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury.
260 _ _ |a New York, NY
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520 _ _ |a Axons in the adult mammalian central nervous system fail to regenerate after spinal cord injury. Neurons lose their capacity to regenerate during development, but the intracellular processes underlying this loss are unclear. We found that critical components of the presynaptic active zone prevent axon regeneration in adult mice. Transcriptomic analysis combined with live-cell imaging revealed that adult primary sensory neurons downregulate molecular constituents of the synapse as they acquire the ability to rapidly grow their axons. Pharmacogenetic reduction of neuronal excitability stimulated axon regeneration after adult spinal cord injury. Genetic gain- and loss-of-function experiments uncovered that essential synaptic vesicle priming proteins of the presynaptic active zone, but not clostridial-toxin-sensitive VAMP-family SNARE proteins, inhibit axon regeneration. Systemic administration of Baclofen reduced voltage-dependent Ca2+ influx in primary sensory neurons and promoted their regeneration after spinal cord injury. These findings indicate that functional presynaptic active zones constitute a major barrier to axon regeneration.
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650 _ 7 |a Baclofen
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650 _ 7 |a Munc13
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650 _ 7 |a RIM1/2
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650 _ 7 |a active zone
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650 _ 7 |a axon injury
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650 _ 7 |a axon regeneration
|2 Other
650 _ 7 |a spinal cord injury
|2 Other
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Axons: metabolism
|2 MeSH
650 _ 2 |a Central Nervous System: metabolism
|2 MeSH
650 _ 2 |a Mammals
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Nerve Regeneration: physiology
|2 MeSH
650 _ 2 |a Neurons: metabolism
|2 MeSH
650 _ 2 |a Spinal Cord Injuries: metabolism
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700 1 _ |a Husch, Andreas
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700 1 _ |a Schaffran, Barbara
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700 1 _ |a Lin, Tien-Chen
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700 1 _ |a Burnside, Emily R
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700 1 _ |a Dupraz, Sebastian
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700 1 _ |a Schelski, Max
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700 1 _ |a Kim, Jisoo
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700 1 _ |a Müller, Johannes Alexander
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700 1 _ |a Schoch, Susanne
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700 1 _ |a Imig, Cordelia
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700 1 _ |a Brose, Nils
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700 1 _ |a Bradke, Frank
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773 _ _ |a 10.1016/j.neuron.2021.10.007
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