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Neuronal Cell Cycle Regulation of Cdk5 in Alzheimer's Disease

Yaqiong Niu, Huifang Li, Karl Herrup and Jie Zhang

Neuronal cell cycle dysregulation is closely related with the neuronal death in Alzheimer’s disease (AD), but the detailed mechanism linking the two processes is unclear. Cyclin-dependent kinase 5 (Cdk5) is described as an atypical Cdk, which has been shown to have no cell cycle promoting activity. Yet while Cdk5 may not promote the cycle, we have found that Cdk5 may play a role in maintaining the quiescent stage of post-mitotic neuron. In this chapter, we review recent findings concerning the cell cycle suppression activity of Cdk5, and relate this function to the initiation and progression of neurodegenerative diseases, in particular AD. Our data suggest that nuclear Cdk5 can block the cell
cycle. When the post-mitotic neuron is subjected to β-amyloid stress, Cdk5 is translocated from nucleus to cytoplasm. Deprived of its nuclear Cdk5, the post-mitotic neuron will re-enter into cell cycle, ultimately leading the cycling neuron to die rather than divide. Our work has identified the molecular basis of the cell cycle suppression effect of Cdk5. Taken together, our data reveal that Cdk5 does indeed regulate cell cycle activity. These finding may provide new pharmacotherapeutic approach to treating brain disorders such as AD.