Chen Jie, Wang Zhong-Feng
Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
Sheng Li Xue Bao. 2010 Aug 25;62(4):295-308.
Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase, and plays multiple roles in neuron development and synaptic plasticity. The active form of Cdk5 is found primarily in the central nervous system (CNS) due to its activator proteins p35 or p39 ubiquitously expressed in neuronal cells. Normally, the transcription and activity of Cdk5 are strictly regulated by several ways. In the physiological condition, Cdk5 plays a key role in the CNS development by phosphorylating the specific serine or threonine site of numerous substrate proteins that are closely associated with the neuronal migration, synaptogenesis, synaptic transmission as well as synaptic plasticity. Under pathological conditions, p35 can be truncated into p25, which can strongly and consistently activate Cdk5, change the cellular localization of Cdk5 and lead to neuronal death ultimately. The increasing evidence has showed that Cdk5 is involved in the pathogenesis of many neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis etc., indicating that Cdk5 may be a potential target in the treatment of the neurodegenerative diseases. In this article, we reviewed the recent progress regarding the roles of Cdk5 in CNS development and neurodegenerative diseases.
细胞周期蛋白依赖性激酶5（Cdk5）是一种脯氨酸导向的丝氨酸/苏氨酸激酶，在神经元发育和突触可塑性中发挥多种作用。由于其激活蛋白p35或p39在神经元细胞中普遍表达，Cdk5的活性形式主要存在于中枢神经系统（CNS）中。通常，Cdk5的转录和活性受到多种方式的严格调控。在生理条件下，Cdk5通过磷酸化与神经元迁移、突触形成、突触传递以及突触可塑性密切相关的众多底物蛋白的特定丝氨酸或苏氨酸位点，在中枢神经系统发育中发挥关键作用。在病理条件下，p35可被截短为p25，p25能强烈且持续地激活Cdk5，改变Cdk5的细胞定位并最终导致神经元死亡。越来越多的证据表明，Cdk5参与了许多神经退行性疾病的发病机制，如阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症等，这表明Cdk5可能是治疗神经退行性疾病的一个潜在靶点。在本文中，我们综述了关于Cdk5在中枢神经系统发育和神经退行性疾病中作用的最新进展。
