Loss of highwire Protects Against the Deleterious Effects of Traumatic Brain Injury in Drosophila Melanogaster
Hill, Ciaran S.
Menon, David K.
Coleman, Michael P.
Frontiers in Neurology
Frontiers Media S.A.
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Hill, C. S., Sreedharan, J., Loreto, A., Menon, D. K., & Coleman, M. P. (2020). Loss of highwire Protects Against the Deleterious Effects of Traumatic Brain Injury in Drosophila Melanogaster. [Other]. 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.
Neurology, wallerian degeneration, traumatic brain injury, neuroprotection, axons, highwire
External DOI: https://doi.org/10.3389/fneur.2020.00401
This record's DOI: https://doi.org/10.17863/CAM.52817