Axon Death Pathways Converge on Axundead to Promote Functional and Structural Axon Disassembly
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Authors
Neukomm, Lukas J.Burdett, Thomas C.
Seeds, Andrew M.
Hampel, Stefanie
Coutinho-Budd, Jaeda
Farley, Jonathan E.
Wong, Jack
Karadeniz, Yonca B.
Osterloh, Jeannette M.
Sheehan, Amy E.
Freeman, Marc R.
Student Authors
Jeannette M. OsterlohThomas C. Burdett
Jonathan Farley
Academic Program
NeuroscienceUMass Chan Affiliations
Graduate School of Biomedical Sciences, Neuroscience ProgramFreeman Lab
Neurobiology
Document Type
Journal ArticlePublication Date
2017-07-05Keywords
Neuroscience and Neurobiology
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Show full item recordAbstract
Axon degeneration is a hallmark of neurodegenerative disease and neural injury. Axotomy activates an intrinsic pro-degenerative axon death signaling cascade involving loss of the NAD+ biosynthetic enzyme Nmnat/Nmnat2 in axons, activation of dSarm/Sarm1, and subsequent Sarm-dependent depletion of NAD+. Here we identify Axundead (Axed) as a mediator of axon death. Axed mutants suppress axon death in several types of axons for the lifespan of the fly and block the pro-degenerative effects of activated dSarm in vivo. Neurodegeneration induced by loss of the sole fly Nmnat ortholog is also fully blocked by axed, but not dsarm, mutants. Thus, pro-degenerative pathways activated by dSarm signaling or Nmnat elimination ultimately converge on Axed. Remarkably, severed axons morphologically preserved by axon death pathway mutations remain integrated in circuits and able to elicit complex behaviors after stimulation, indicating that blockade of axon death signaling results in long-term functional preservation of axons.Source
Neuron. 2017 Jul 5;95(1):78-91.e5. doi: 10.1016/j.neuron.2017.06.031. Link to article on publisher's siteDOI
10.1016/j.neuron.2017.06.031Permanent Link to this Item
http://hdl.handle.net/20.500.14038/37941PubMed ID
28683272Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.neuron.2017.06.031