Attenuating the DNA damage response to double-strand breaks restores function in models of CNS neurodegeneration. / Tuxworth , Richard ; Taylor, Matthew ; Anduaga, Ane Martin ; Hussien-Ali, Al; Chatzimatthaiou, Sotiroula ; Longland, Joanne ; Thompson, Adam; Almutiri, Sharif ; Alifragis, Pavlos; Kyriacou, Charalambos ; Kysela, Boris ; Ahmed, Zubair .

In: Brain Communications, Vol. 1, No. 1, fcz005, 02.07.2019, p. 1-21.

Research output: Contribution to journalArticle

Published

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Attenuating the DNA damage response to double-strand breaks restores function in models of CNS neurodegeneration. / Tuxworth , Richard ; Taylor, Matthew ; Anduaga, Ane Martin ; Hussien-Ali, Al; Chatzimatthaiou, Sotiroula ; Longland, Joanne ; Thompson, Adam; Almutiri, Sharif ; Alifragis, Pavlos; Kyriacou, Charalambos ; Kysela, Boris ; Ahmed, Zubair .

In: Brain Communications, Vol. 1, No. 1, fcz005, 02.07.2019, p. 1-21.

Research output: Contribution to journalArticle

Harvard

Tuxworth , R, Taylor, M, Anduaga, AM, Hussien-Ali, A, Chatzimatthaiou, S, Longland, J, Thompson, A, Almutiri, S, Alifragis, P, Kyriacou, C, Kysela, B & Ahmed, Z 2019, 'Attenuating the DNA damage response to double-strand breaks restores function in models of CNS neurodegeneration', Brain Communications, vol. 1, no. 1, fcz005, pp. 1-21. https://doi.org/10.1093/braincomms/fcz005

APA

Tuxworth , R., Taylor, M., Anduaga, A. M., Hussien-Ali, A., Chatzimatthaiou, S., Longland, J., ... Ahmed, Z. (2019). Attenuating the DNA damage response to double-strand breaks restores function in models of CNS neurodegeneration. Brain Communications, 1(1), 1-21. [fcz005]. https://doi.org/10.1093/braincomms/fcz005

Vancouver

Tuxworth R, Taylor M, Anduaga AM, Hussien-Ali A, Chatzimatthaiou S, Longland J et al. Attenuating the DNA damage response to double-strand breaks restores function in models of CNS neurodegeneration. Brain Communications. 2019 Jul 2;1(1):1-21. fcz005. https://doi.org/10.1093/braincomms/fcz005

Author

Tuxworth , Richard ; Taylor, Matthew ; Anduaga, Ane Martin ; Hussien-Ali, Al ; Chatzimatthaiou, Sotiroula ; Longland, Joanne ; Thompson, Adam ; Almutiri, Sharif ; Alifragis, Pavlos ; Kyriacou, Charalambos ; Kysela, Boris ; Ahmed, Zubair . / Attenuating the DNA damage response to double-strand breaks restores function in models of CNS neurodegeneration. In: Brain Communications. 2019 ; Vol. 1, No. 1. pp. 1-21.

BibTeX

@article{30e7ad57a8a7467982c0112de642225d,
title = "Attenuating the DNA damage response to double-strand breaks restores function in models of CNS neurodegeneration",
abstract = "DNA double-strand breaks are a feature of many acute and long-term neurological disorders, including neurodegeneration, following neurotrauma and after stroke. Persistent activation of the DNA damage response in response to double-strand breaks contributes to neural dysfunction and pathology as it can force post-mitotic neurons to re-enter the cell cycle leading to senescence or apoptosis. Mature, non-dividing neurons may tolerate low levels of DNA damage, in which case muting the DNA damage response might be neuroprotective. Here, we show that attenuating the DNA damage response by targeting the meiotic recombination 11, Rad50, Nijmegen breakage syndrome 1 complex, which is involved in double-strand break recognition, is neuroprotective in three neurodegeneration models in Drosophila and prevents Aβ1-42-induced loss of synapses in embryonic hippocampal neurons. Attenuating the DNA damage response after optic nerve injury is also neuroprotective to retinal ganglion cells and promotes dramatic regeneration of their neurites both in vitro and in vivo. Dorsal root ganglion neurons similarly regenerate when the DNA damage response is targeted in vitro and in vivo and this strategy also induces significant restoration of lost function after spinal cord injury. We conclude that muting the DNA damage response in the nervous system is neuroprotective in multiple neurological disorders. Our results point to new therapies to maintain or repair the nervous system.",
author = "Richard Tuxworth and Matthew Taylor and Anduaga, {Ane Martin} and Al Hussien-Ali and Sotiroula Chatzimatthaiou and Joanne Longland and Adam Thompson and Sharif Almutiri and Pavlos Alifragis and Charalambos Kyriacou and Boris Kysela and Zubair Ahmed",
year = "2019",
month = "7",
day = "2",
doi = "10.1093/braincomms/fcz005",
language = "English",
volume = "1",
pages = "1--21",
journal = "Brain Communications",
number = "1",

}

RIS

TY - JOUR

T1 - Attenuating the DNA damage response to double-strand breaks restores function in models of CNS neurodegeneration

AU - Tuxworth , Richard

AU - Taylor, Matthew

AU - Anduaga, Ane Martin

AU - Hussien-Ali, Al

AU - Chatzimatthaiou, Sotiroula

AU - Longland, Joanne

AU - Thompson, Adam

AU - Almutiri, Sharif

AU - Alifragis, Pavlos

AU - Kyriacou, Charalambos

AU - Kysela, Boris

AU - Ahmed, Zubair

PY - 2019/7/2

Y1 - 2019/7/2

N2 - DNA double-strand breaks are a feature of many acute and long-term neurological disorders, including neurodegeneration, following neurotrauma and after stroke. Persistent activation of the DNA damage response in response to double-strand breaks contributes to neural dysfunction and pathology as it can force post-mitotic neurons to re-enter the cell cycle leading to senescence or apoptosis. Mature, non-dividing neurons may tolerate low levels of DNA damage, in which case muting the DNA damage response might be neuroprotective. Here, we show that attenuating the DNA damage response by targeting the meiotic recombination 11, Rad50, Nijmegen breakage syndrome 1 complex, which is involved in double-strand break recognition, is neuroprotective in three neurodegeneration models in Drosophila and prevents Aβ1-42-induced loss of synapses in embryonic hippocampal neurons. Attenuating the DNA damage response after optic nerve injury is also neuroprotective to retinal ganglion cells and promotes dramatic regeneration of their neurites both in vitro and in vivo. Dorsal root ganglion neurons similarly regenerate when the DNA damage response is targeted in vitro and in vivo and this strategy also induces significant restoration of lost function after spinal cord injury. We conclude that muting the DNA damage response in the nervous system is neuroprotective in multiple neurological disorders. Our results point to new therapies to maintain or repair the nervous system.

AB - DNA double-strand breaks are a feature of many acute and long-term neurological disorders, including neurodegeneration, following neurotrauma and after stroke. Persistent activation of the DNA damage response in response to double-strand breaks contributes to neural dysfunction and pathology as it can force post-mitotic neurons to re-enter the cell cycle leading to senescence or apoptosis. Mature, non-dividing neurons may tolerate low levels of DNA damage, in which case muting the DNA damage response might be neuroprotective. Here, we show that attenuating the DNA damage response by targeting the meiotic recombination 11, Rad50, Nijmegen breakage syndrome 1 complex, which is involved in double-strand break recognition, is neuroprotective in three neurodegeneration models in Drosophila and prevents Aβ1-42-induced loss of synapses in embryonic hippocampal neurons. Attenuating the DNA damage response after optic nerve injury is also neuroprotective to retinal ganglion cells and promotes dramatic regeneration of their neurites both in vitro and in vivo. Dorsal root ganglion neurons similarly regenerate when the DNA damage response is targeted in vitro and in vivo and this strategy also induces significant restoration of lost function after spinal cord injury. We conclude that muting the DNA damage response in the nervous system is neuroprotective in multiple neurological disorders. Our results point to new therapies to maintain or repair the nervous system.

U2 - 10.1093/braincomms/fcz005

DO - 10.1093/braincomms/fcz005

M3 - Article

VL - 1

SP - 1

EP - 21

JO - Brain Communications

JF - Brain Communications

IS - 1

M1 - fcz005

ER -