Article (Scientific journals)
Genetic and pharmacological inhibition of Cdk1 provides neuroprotection towards ischemic neuronal death
Marlier, Quentin; Jibassia, Florian; Verteneuil, Sébastien et al.
2018In Cell Death Discovery
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Abstract :
[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Marlier, Quentin ;  Université de Liège - ULiège > GIGA - Neurosciences
Jibassia, Florian 
Verteneuil, Sébastien ;  Université de Liège - ULiège > GIGA - Neurosciences
Linden, Jérôme ;  Université de Liège - ULiège > Département de Psychologie > Psychologie de l'apprentissage et cognition animale
Kaldis, Philipp
Meijer, Laurent
Nguyen, Laurent  
Vandenbosch, Renaud   ;  Université de Liège - ULiège > GIGA - Neurosciences
Malgrange, Brigitte   ;  Université de Liège - ULiège > GIGA - Neurosciences
 These authors have contributed equally to this work.
Language :
English
Title :
Genetic and pharmacological inhibition of Cdk1 provides neuroprotection towards ischemic neuronal death
Publication date :
2018
Journal title :
Cell Death Discovery
eISSN :
2058-7716
Publisher :
Nature
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 19 March 2018

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