Roles of cyclin-dependent kinase 5 in central nervous system development and neurodegenerative diseases / 生理学报

ABSTRACT

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.