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

被引:11
|
作者
Hill, Ciaran S. [1 ,2 ]
Sreedharan, Jemeen [2 ,3 ]
Loreto, Andrea [1 ]
Menon, David K. [4 ,5 ]
Coleman, Michael P. [1 ,2 ]
机构
[1] Univ Cambridge, John van Geest Ctr Brain Repair, Cambridge, England
[2] Babraham Inst, Cambridge, England
[3] Kings Coll London, Inst Psychiat, London, England
[4] Univ Cambridge, Div Anaesthesia, Dept Med, Cambridge, England
[5] Univ Cambridge, Wolfson Brain Imaging Ctr, Dept Clin Neurosci, Cambridge, England
来源
FRONTIERS IN NEUROLOGY | 2020年 / 11卷
基金
英国惠康基金;
关键词
wallerian degeneration; traumatic brain injury; neuroprotection; axons; highwire; NICOTINAMIDE MONONUCLEOTIDE ADENYLYLTRANSFERASE; AXONAL INJURY; WALLERIAN DEGENERATION; SYNAPTIC GROWTH; NMNAT; MODEL; DISCONNECTION; CHAPERONE; INSIGHTS; SYNTHASE;
D O I
10.3389/fneur.2020.00401
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页数:11
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