Genetic and pharmacological inhibition of Cdk1 provides neuroprotection towards ischemic neuronal death
Marlier, Quentin ; Jibassia, Florian ; Verteneuil, Sébastien ; Linden, Jérôme ; Kaldis, Philipp LU
; Meijer, Laurent
; Nguyen, Laurent
; Vandenbosch, Renaud
and Malgrange, Brigitte
(2018)
In Cell death discovery
4(43).
p.1-12
- Abstract
Cell cycle proteins are mainly expressed by dividing cells. However, it is well established that these molecules play additional non-canonical activities in several cell death contexts. Increasing evidence shows expression of cell cycle regulating proteins in post-mitotic cells, including mature neurons, following neuronal insult. Several cyclin-dependent kinases (Cdks) have already been shown to mediate ischemic neuronal death but Cdk1, a major cell cycle G2/M regulator, has not been investigated in this context. We therefore examined the role of Cdk1 in neuronal cell death following cerebral ischemia, using both in vitro and in vivo genetic and pharmacological approaches. Exposure of primary cortical neurons cultures to 4 h of... (More)
Cell cycle proteins are mainly expressed by dividing cells. However, it is well established that these molecules play additional non-canonical activities in several cell death contexts. Increasing evidence shows expression of cell cycle regulating proteins in post-mitotic cells, including mature neurons, following neuronal insult. Several cyclin-dependent kinases (Cdks) have already been shown to mediate ischemic neuronal death but Cdk1, a major cell cycle G2/M regulator, has not been investigated in this context. We therefore examined the role of Cdk1 in neuronal cell death following cerebral ischemia, using both in vitro and in vivo genetic and pharmacological approaches. Exposure of primary cortical neurons cultures to 4 h of oxygen-glucose deprivation (OGD) resulted in neuronal cell death and induced Cdk1 expression. Neurons from Cdk1-cKO mice showed partial resistance to OGD-induced neuronal cell death. Addition of R-roscovitine to the culture medium conferred neuroprotection against OGD-induced neuronal death. Transient 1-h occlusion of the cerebral artery (MCAO) also leads to Cdk1 expression and activation. Cdk1-cKO mice displayed partial resistance to transient 1-h MCAO. Moreover, systemic delivery of R-roscovitine was neuroprotective following transient 1-h MCAO. This study demonstrates that promising neuroprotective therapies can be considered through inhibition of the cell cycle machinery and particularly through pharmacological inhibition of Cdk1.
(Less)
- author
- Marlier, Quentin
; Jibassia, Florian
; Verteneuil, Sébastien
; Linden, Jérôme
; Kaldis, Philipp
LU
; Meijer, Laurent
; Nguyen, Laurent
; Vandenbosch, Renaud
and Malgrange, Brigitte
- publishing date
- 2018-03-16
- type
- Contribution to journal
- publication status
- published
- in
- Cell death discovery
- volume
- 4
- issue
- 43
- pages
- 1 - 12
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:29581894
- scopus:85071124316
- ISSN
- 2058-7716
- DOI
- 10.1038/s41420-018-0044-7
- language
- English
- LU publication?
- no
- id
- e18b3495-067f-4e31-9e0c-0d1fa2cd480a
- date added to LUP
- 2019-09-17 14:50:11
- date last changed
- 2024-04-30 21:26:06
@article{e18b3495-067f-4e31-9e0c-0d1fa2cd480a,
abstract = {{<p>Cell cycle proteins are mainly expressed by dividing cells. However, it is well established that these molecules play additional non-canonical activities in several cell death contexts. Increasing evidence shows expression of cell cycle regulating proteins in post-mitotic cells, including mature neurons, following neuronal insult. Several cyclin-dependent kinases (Cdks) have already been shown to mediate ischemic neuronal death but Cdk1, a major cell cycle G2/M regulator, has not been investigated in this context. We therefore examined the role of Cdk1 in neuronal cell death following cerebral ischemia, using both in vitro and in vivo genetic and pharmacological approaches. Exposure of primary cortical neurons cultures to 4 h of oxygen-glucose deprivation (OGD) resulted in neuronal cell death and induced Cdk1 expression. Neurons from Cdk1-cKO mice showed partial resistance to OGD-induced neuronal cell death. Addition of R-roscovitine to the culture medium conferred neuroprotection against OGD-induced neuronal death. Transient 1-h occlusion of the cerebral artery (MCAO) also leads to Cdk1 expression and activation. Cdk1-cKO mice displayed partial resistance to transient 1-h MCAO. Moreover, systemic delivery of R-roscovitine was neuroprotective following transient 1-h MCAO. This study demonstrates that promising neuroprotective therapies can be considered through inhibition of the cell cycle machinery and particularly through pharmacological inhibition of Cdk1.</p>}},
author = {{Marlier, Quentin and Jibassia, Florian and Verteneuil, Sébastien and Linden, Jérôme and Kaldis, Philipp and Meijer, Laurent and Nguyen, Laurent and Vandenbosch, Renaud and Malgrange, Brigitte}},
issn = {{2058-7716}},
language = {{eng}},
month = {{03}},
number = {{43}},
pages = {{1--12}},
publisher = {{Nature Publishing Group}},
series = {{Cell death discovery}},
title = {{Genetic and pharmacological inhibition of Cdk1 provides neuroprotection towards ischemic neuronal death}},
url = {{http://dx.doi.org/10.1038/s41420-018-0044-7}},
doi = {{10.1038/s41420-018-0044-7}},
volume = {{4}},
year = {{2018}},
}