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

• Published in: Mechanisms of ageing and development Vol. 132; no. 8; pp. 389 - 394
• Main Authors: Zhu, Jinqiu, Li, Wenming, Mao, Zixu
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.08.2011; Elsevier
• Subjects: Aging; Animals; Biological and medical sciences; Cdk5; Cell death; Cell Death - genetics; Cell migration; Cell Movement - genetics; Cell survival; Cell Survival - genetics; Central nervous system; Cyclin-dependent kinase; Cyclin-dependent kinase 5; Cyclin-Dependent Kinase 5 - genetics; Cyclin-Dependent Kinase 5 - metabolism; Development. Metamorphosis. Moult. Ageing; Differentiation; DNA Damage; Fundamental and applied biological sciences. Psychology; Humans; Neurodegenerative disease; Neurodegenerative diseases; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; Neuronal Plasticity - genetics; Neurons - metabolism; Neurotransmission; Plasticity (synaptic); Synaptic Transmission - genetics; Synaptogenesis; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Neurodegenerative disease; Cdk5; Cell death; DNA damage; Central nervous system; Vertebrata; Senescence; Mammalia; Neuron; DNA; Development; Degenerative disease
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2011.04.011

► 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. 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.