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

Ciaran S. Hill; Jemeen Sreedharan; Andrea Loreto; David K. Menon; Michael P. Coleman

doi:10.3389/fneur.2020.00401

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

Ciaran S. Hill^*, Jemeen Sreedharan, Andrea Loreto, David K. Menon, Michael P. Coleman

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

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.

Original language	English
Article number	401
Journal	Frontiers in Neurology
Volume	11
DOIs	https://doi.org/10.3389/fneur.2020.00401
Publication status	Published - 12 May 2020

Keywords

axons
highwire
neuroprotection
traumatic brain injury
wallerian degeneration

Access to Document

10.3389/fneur.2020.00401

Cite this

@article{e472f3e32cce463dbc55d2c745b9684e,

title = "Loss of highwire Protects Against the Deleterious Effects of Traumatic Brain Injury in Drosophila Melanogaster",

abstract = "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.",

keywords = "axons, highwire, neuroprotection, traumatic brain injury, wallerian degeneration",

author = "Hill, {Ciaran S.} and Jemeen Sreedharan and Andrea Loreto and Menon, {David K.} and Coleman, {Michael P.}",

year = "2020",

month = may,

day = "12",

doi = "10.3389/fneur.2020.00401",

language = "English",

volume = "11",

journal = "Frontiers in Neurology",

issn = "1664-2295",

publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - Loss of highwire Protects Against the Deleterious Effects of Traumatic Brain Injury in Drosophila Melanogaster

AU - Hill, Ciaran S.

AU - Sreedharan, Jemeen

AU - Loreto, Andrea

AU - Menon, David K.

AU - Coleman, Michael P.

PY - 2020/5/12

Y1 - 2020/5/12

N2 - 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.

AB - 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.

KW - axons

KW - highwire

KW - neuroprotection

KW - traumatic brain injury

KW - wallerian degeneration

UR - http://www.scopus.com/inward/record.url?scp=85085299546&partnerID=8YFLogxK

U2 - 10.3389/fneur.2020.00401

DO - 10.3389/fneur.2020.00401

M3 - Article

AN - SCOPUS:85085299546

SN - 1664-2295

VL - 11

JO - Frontiers in Neurology

JF - Frontiers in Neurology

M1 - 401

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this