This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research article
Ciaran Scott Hill
University of Cambridge
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4488-4034
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Traumatic brain injury (TBI) is a major global cause of death and disability. Axonal injury is a major underlying mechanism of TBI and could represent a major therapeutic target. We provide evidence that targeting the axonal death pathway known as Wallerian degeneration (WD) improves outcome in a Drosophila Melanogaster model of high impact trauma. This cell-autonomous neurodegenerative pathway is initiated following axon injury, and in Drosophila, involves activity of the E3 ubiquitin ligase highwire. In this study we explore the effects of that a loss-of-function mutation in the highwire gene has on a range of outcomes following high impact trauma.
Results
Results demonstrate that a loss-of-function mutation in the highwire gene rescues deleterious effects of a traumatic injury, including - improved functional outcomes including climbing ability and flight maintenance, lifespan, survival of a subset of dopaminergic neurons, and retention of synaptic proteins.
Conclusion
We demonstrate that a loss-of-function mutation in the highwire gene rescues deleterious effects of a traumatic injury. This data suggests that highwire represents a potential therapeutic target in traumatic injury.
Keywords
Wallerian degeneration, traumatic brain injury, neuroprotection, axons, highwire
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 20 Mar, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This is a preprint. It has not completed peer review.
Research article
Ciaran Scott Hill
University of Cambridge
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4488-4034
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 20 Mar, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Traumatic brain injury (TBI) is a major global cause of death and disability. Axonal injury is a major underlying mechanism of TBI and could represent a major therapeutic target. We provide evidence that targeting the axonal death pathway known as Wallerian degeneration (WD) improves outcome in a Drosophila Melanogaster model of high impact trauma. This cell-autonomous neurodegenerative pathway is initiated following axon injury, and in Drosophila, involves activity of the E3 ubiquitin ligase highwire. In this study we explore the effects of that a loss-of-function mutation in the highwire gene has on a range of outcomes following high impact trauma.
Results
Results demonstrate that a loss-of-function mutation in the highwire gene rescues deleterious effects of a traumatic injury, including - improved functional outcomes including climbing ability and flight maintenance, lifespan, survival of a subset of dopaminergic neurons, and retention of synaptic proteins.
Conclusion
We demonstrate that a loss-of-function mutation in the highwire gene rescues deleterious effects of a traumatic injury. This data suggests that highwire represents a potential therapeutic target in traumatic injury.
Figure 1
Figure 2
Figure 3
Figure 4
Loading...