Suppression of nucleocytoplasmic p27Kip1 export attenuates CDK4-mediated neuronal death induced by status epilepticus

  title={Suppression of nucleocytoplasmic p27Kip1 export attenuates CDK4-mediated neuronal death induced by status epilepticus},
  author={Ji-Eun Kim and Tae-Cheon Kang},
  journal={Neuroscience Research},
Aberrant cell cycle re-entry promotes neuronal death in various neurological diseases. Thus, cyclin-dependent kinases (CDKs) seem to be one of potential therapeutic targets to prevent neuronal loss. In the present study, we investigated the involvements of CDK4, CDK5 and p27Kip1 (an endogenous CDK inhibitor) in status epilepticus (SE)-induced neuronal death. Following SE, CDK4 expression was increased in CA1 neurons, while CDK5 was decreased. Most of TUNEL-positive neurons showed CDK4… Expand


LIM kinase-2 induces programmed necrotic neuronal death via dysfunction of DRP1-mediated mitochondrial fission
It is suggested that the ROCK-p27Kip1-cyclin D1/CDK4-LIMK2-DRP1-mediated programmed necrosis may be new therapeutic targets for neuronal death. Expand
Cdk5 Nuclear Localization Is p27-dependent in Nerve Cells
A model in which Cdk5 exerts a double protective function in neurons: chronically suppressing the cell cycle when located in the nucleus and transiently delaying cell death in the cytoplasm is suggested. Expand
Cdk5-mediated inhibition of APC/C-Cdh1 switches on the cyclin D1-Cdk4-pRb pathway causing aberrant S-phase entry of postmitotic neurons
The results indicate that APC/C-Cdh1 actively suppresses an aberrant cell cycle entry and death of neurons, highlighting its critical function in neuroprotection. Expand
Cell Cycle Regulators in the Neuronal Death Pathway of Amyotrophic Lateral Sclerosis Caused by Mutant Superoxide Dismutase 1
Results indicate that a cell cycle signaling at the neuronal G1-S checkpoint subsequent to Cdk5 deregulation may constitute a critical step of the neuronal death pathway in ALS caused by mutant SOD1. Expand
Cyclin-dependent kinase 5 (CDK5) and neuronal cell death
Current knowledge about the involvement of CDK5 in neuronal cell death is summarized, potential therapeutic options that might arise from the identification ofCDK5 as an important upstream element of neuronal cellDeath cascades are discussed and possible up- or downstream partners of CDk5 are discussed. Expand
CDK5 inhibitors prevent astroglial apoptosis and reactive astrogliosis by regulating PKA and DRP1 phosphorylations in the rat hippocampus
In the present study, both olomoucine and roscovitine (CDK5 inhibitor) effectively ameliorated SE-induced astroglial apoptosis in the dentate gyrus without changed seizure susceptibility and suggest that CDK5 inhibitors may mitigate astrogled apoptosis and reactive astrogLiosis accompanied by modulations of DRP1-mediated mitochondrial dynamics. Expand
p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21
Using a yeast interaction screen to search for proteins that interact with cyclin D1-Cdk4, we identified a 27 kDa mouse protein related to the p21 cyclin-Cdk inhibitor. p27 interacts strongly withExpand
Cell cycle molecules and vertebrate neuron death: E2F at the hub
The discovery and elaboration of the neuronal apoptotic E2F pathway provides abundant targets as well as small molecule candidates for potential therapeutic intervention in nervous system trauma and degenerative disease. Expand
PARP1 activation/expression modulates regional-specific neuronal and glial responses to seizure in a hemodynamic-independent manner
The findings suggest that the cellular-specific PARP1 activation/degradation may distinctly involve regional-specific neuronal damage, astroglial death and reactive gliosis in response to SE independently of hemodynamics. Expand
Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation
It is reported that conditional knockout of Cdk5 in the adult mouse brain improved performance in spatial learning tasks and enhanced hippocampal long-term potentiation and NMDA receptor (NMDAR)-mediated excitatory postsynaptic currents. Expand