细胞周期蛋白依赖性激酶5是帕金森病小鼠模型中多巴胺能神经元损失的一个介质。
Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson's disease.
作者信息
Smith Patrice D, Crocker Stephen J, Jackson-Lewis Vernice, Jordan-Sciutto Kelly L, Hayley Shawn, Mount Matthew P, O'Hare Michael J, Callaghan Steven, Slack Ruth S, Przedborski Serge, Anisman Hymie, Park David S
机构信息
Neuroscience Group, Ottawa Health Research Institute, Ottawa, ON, Canada K1H 8M5.
出版信息
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13650-5. doi: 10.1073/pnas.2232515100. Epub 2003 Oct 31.
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.
摘要
最近的证据表明，细胞周期蛋白依赖性激酶（CDKs，cdks）可能在几种神经退行性疾病中被异常激活。在此，我们报告，在给予1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）后，cdk5的表达和活性升高，MPTP是一种损害黑质纹状体多巴胺能通路的毒素。一般的cdk抑制剂黄酮哌啶醇、显性负性cdk5的表达，以及在较小程度上显性负性cdk2的表达，可减轻MPTP引起的多巴胺能神经元损失，这些发现支持了cdk5改变的致病意义。此外，CDK抑制策略可减轻MPTP诱导的运动减少以及与纹状体多巴胺无关的纹状体功能标志物。我们提出，cdk5是帕金森病中多巴胺能神经元变性的关键调节因子。
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