AUTHOR=Hill Ciaran S. , Sreedharan Jemeen , Loreto Andrea , Menon David K. , Coleman Michael P. 

TITLE=Loss of highwire Protects Against the Deleterious Effects of Traumatic Brain Injury in Drosophila Melanogaster

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00401

DOI=10.3389/fneur.2020.00401

ISSN=1664-2295

ABSTRACT=<p>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 <italic>Drosophila Melanogaster</italic> 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 <italic>highwire</italic>. We demonstrate that a loss-of-function mutation in the <italic>highwire</italic> 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 <italic>highwire</italic> represents a potential therapeutic target in traumatic injury.</p>