| Literature DB >> 14595022 |
Patrice D Smith1, Stephen J Crocker, Vernice Jackson-Lewis, Kelly L Jordan-Sciutto, Shawn Hayley, Matthew P Mount, Michael J O'Hare, Steven Callaghan, Ruth S Slack, Serge Przedborski, Hymie Anisman, David S Park.
Abstract
Recent evidence indicates that cyclin-dependent kinases (CDKs, cdks) may be inappropriately activated in several neurodegenerative conditions. Here, we report that cdk5 expression and activity are elevated after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin that damages the nigrostriatal dopaminergic pathway. Supporting the pathogenic significance of the cdk5 alterations are the findings that the general cdk inhibitor, flavopiridol, or expression of dominant-negative cdk5, and to a lesser extent dominant-negative cdk2, attenuates the loss of dopaminergic neurons caused by MPTP. In addition, CDK inhibition strategies attenuate MPTP-induced hypolocomotion and markers of striatal function independent of striatal dopamine. We propose that cdk5 is a key regulator in the degeneration of dopaminergic neurons in Parkinson's disease.Entities:
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Year: 2003 PMID： 14595022 PMCID： PMC263868 DOI： 10.1073/pnas.2232515100
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205