RGD Reference Report - Ischemic stroke injury is mediated by aberrant Cdk5. - Rat Genome Database
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Ischemic stroke injury is mediated by aberrant Cdk5.

Authors: Meyer, Douglas A  Torres-Altoro, Melissa I  Tan, Zhenjun  Tozzi, Alessandro  Di Filippo, Massimiliano  DiNapoli, Vincent  Plattner, Florian  Kansy, Janice W  Benkovic, Stanley A  Huber, Jason D  Miller, Diane B  Greengard, Paul  Calabresi, Paolo  Rosen, Charles L  Bibb, James A 
Citation: Meyer DA, etal., J Neurosci. 2014 Jun 11;34(24):8259-67. doi: 10.1523/JNEUROSCI.4368-13.2014.
RGD ID: 13782375
Pubmed: (View Article at PubMed) PMID:24920629
DOI: Full-text: DOI:10.1523/JNEUROSCI.4368-13.2014

Ischemic stroke is one of the leading causes of morbidity and mortality. Treatment options are limited and only a minority of patients receive acute interventions. Understanding the mechanisms that mediate neuronal injury and death may identify targets for neuroprotective treatments. Here we show that the aberrant activity of the protein kinase Cdk5 is a principal cause of neuronal death in rodents during stroke. Ischemia induced either by embolic middle cerebral artery occlusion (MCAO) in vivo or by oxygen and glucose deprivation in brain slices caused calpain-dependent conversion of the Cdk5-activating cofactor p35 to p25. Inhibition of aberrant Cdk5 during ischemia protected dopamine neurotransmission, maintained field potentials, and blocked excitotoxicity. Furthermore, pharmacological inhibition or conditional knock-out (CKO) of Cdk5 prevented neuronal death in response to ischemia. Moreover, Cdk5 CKO dramatically reduced infarctions following MCAO. Thus, targeting aberrant Cdk5 activity may serve as an effective treatment for stroke.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Cdk5  (cyclin-dependent kinase 5)

Genes (Mus musculus)
Cdk5  (cyclin-dependent kinase 5)

Genes (Homo sapiens)
CDK5  (cyclin dependent kinase 5)


Additional Information