1. Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson's disease
- Author
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Smith, P. (Patrice D.), Crocker, S.J. (Stephen J.), Jackson-Lewis, V. (Vernice), Jordan-Sciutto, K.L. (Kelly L.), Hayley, S. (Shawn), Mount, M.P. (Matthew P.), O'Hare, M.J. (Michael J.), Callaghan, S. (Steven), Slack, R.S. (Ruth S.), Przedborski, S. (Serge), Anisman, H. (Hymie), Park, D.S. (David S.), Smith, P. (Patrice D.), Crocker, S.J. (Stephen J.), Jackson-Lewis, V. (Vernice), Jordan-Sciutto, K.L. (Kelly L.), Hayley, S. (Shawn), Mount, M.P. (Matthew P.), O'Hare, M.J. (Michael J.), Callaghan, S. (Steven), Slack, R.S. (Ruth S.), Przedborski, S. (Serge), Anisman, H. (Hymie), and Park, D.S. (David S.)
- 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 dopaminerg
- Published
- 2003
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