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[Roles of cyclin-dependent kinase 5 in central nervous system development and neurodegenerative diseases.] [Ariticle in Chinese]

CHEN Jie, WANG Zhong-Feng^*

Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China

Abstract

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase, and plays multiple roles in neuron developmentand synaptic plasticity. The active form of Cdk5 is found primarily in the central nervous system (CNS) due to its activatorproteins p35 or p39 ubiquitously expressed in neuronal cells. Normally, the transcription and activity of Cdk5 are strictly regulated byseveral ways. In the physiological condition, Cdk5 plays a key role in the CNS development by phosphorylating the specific serine orthreonine site of numerous substrate proteins that are closely associated with the neuronal migration, synaptogenesis, synaptictransmission as well as synaptic plasticity. Under pathological conditions, p35 can be truncated into p25, which can strongly andconsistently activate Cdk5, change the cellular localization of Cdk5 and lead to neuronal death ultimately. The increasing evidence hasshowed that Cdk5 is involved in the pathogenesis of many neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’sdisease, Huntington’s disease and amyotrophic lateral sclerosis etc., indicating that Cdk5 may be a potential target in the treatment ofthe neurodegenerative diseases. In this article, we reviewed the recent progress regarding the roles of Cdk5 in CNS development andneurodegenerative diseases.

Key words: cyclin-dependent kinase 5; p35; p25; synaptic transmission; synaptic plasticity; neuronal survival; neuronal death; neurodegenerative diseases

Received: 2010-06-30　　Accepted: 2010-07-30

Corresponding author: 王中峰　　E-mail: zfwang@fudan.edu.cn

Citing This Article：

CHEN Jie, WANG Zhong-Feng. [Roles of cyclin-dependent kinase 5 in central nervous system development and neurodegenerative diseases.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (4): 295-308 (in Chinese with English abstract).