Cdk5: Mediator of neuronal development, death and the response to DNA damage

In the central nervous system, cyclin-dependent kinase 5 (Cdk5), an unusual member of the Cdk family, is implicated in the regulation of various physiological processes ranging from neuronal survival, migration and differentiation, to synaptogenesis, synaptic plasticity and neurotransmission. Dysregulation of this kinase has been demonstrated to play a critical role in the pathogenic process of neurodegenerative disorders. DNA damage is emerging as an important pathological component in various neurodegenerative conditions. In this review, we discuss the recent progress regarding the regulation and roles of Cdk5 under physiological conditions, and its dysregulation under pathological conditions, especially in neuronal death mediated by DNA damage.

► Cdk5 plays a key role in the normal development of the CNS.
► Dysregulation of Cdk5 is neurotoxic and contributes to the pathogenesis of neurodegenerative disorders.
► Neuronal DNA damage is related to the aging of the human brain.
► DNA damage response mediated by Cdk5 is a critical pathological component during neurodegeneration.