Loss of highwire Protects Against the Deleterious Effects of Traumatic Brain Injury in Drosophila Melanogaster.
Hill, Ciaran S
Menon, David K
Frontiers Media SA
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Hill, C. S., Sreedharan, J., Loreto, A., Menon, D. K., & Coleman, M. (2020). Loss of highwire Protects Against the Deleterious Effects of Traumatic Brain Injury in Drosophila Melanogaster.. Front Neurol, 11 401. https://doi.org/10.3389/fneur.2020.00401
Traumatic brain injury 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 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. We demonstrate that a loss-of-function mutation in the highwire gene rescues deleterious effects of a traumatic injury, including-improved functional outcomes, lifespan, survival of dopaminergic neurons, and retention of synaptic proteins. This data suggests that highwire represents a potential therapeutic target in traumatic injury.
European Commission (602150)
Parkinson's UK (G-1602)
Wellcome Trust (210904/Z/18/Z)
External DOI: https://doi.org/10.3389/fneur.2020.00401
This record's URL: https://www.repository.cam.ac.uk/handle/1810/307887
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/