Cerebral ischemia, cell cycle elements and Cdk5.
Stroke is a devastating disorder that significantly contributes to death, disability, and healthcare costs. New therapeutic strategies have been recently focusing on the development of neuroprotective agents that could halt the underlying mechanisms of neuronal death leading to brain damage. Accumulating evidence implicates proteins that are normally involved in the regulation of the cell cycle to neuronal death following ischemic insult, suggesting that these proteins could be suitable targets for stroke therapy. In this brief review, we present in vitro and in vivo arguments linking cell cycle molecules, i.e., cyclins, mitotic cyclin-dependent kinases (Cdks), as well as non-mitotic Cdk5, to ischemic neuronal death. We also report the evaluation of the potential of Cdk inhibitors as neuroprotective strategy for ischemic injury.
Timsit
Serge
S
Faculté de Médecine et des Sciences de la Santé de Brest, Brest, France. serge.timsit@chu-brest.fr
Menn
Bénédicte
B
D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology*; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human