The Role of Cyclin-Dependent Kinase 5 (Cdk5) in Neurodegeneration

The Role of Cyclin-Dependent Kinase 5 (Cdk5) in Neurodegeneration

Miniaci Performing Arts Center

The purpose of this literature research project is to investigate the role of Cyclin- dependent kinase 5 (Cdk5) in neurodegenerative diseases by summarizing its function in brain development, learning and memory. Cdk5 is a proline directed protein kinase that phosphorylates serine and threonine residues. Additionally the role of Cdk5 in the regulation of NMDA receptor, N-cadherin-mediated adhesion as well as the drugs that inhibit their normal functions will be examined. Recent studies regarding neurodegenerative pathology of diseases such as Alzheimer’s, Parkinson’s and Amyotrophic lateral sclerosis reveled a crucial role of this kinase in central nervous system development, particularly in the normal positioning of neurons, axonal guidance, synaptic plasticity, dopamine signaling, cell adhesion and vesicle trafficking as well as neurodegenerative and neurofibrillary tangle diseases. Cdk5 is regulated by the binding of either p35 or p39, which serve as activators of Cdk5 which proteolytically cleave the two regulatory subunits into p25 and p29 respectively. Accumulation of the p25 subunit has been specifically identified in the neurons of Alzheimer’s as well as other neurodegenerative diseases where the accumulation of p25 serves as a competitive activator of Cdk5 altering the normal substrate specificity of Cdk5 which then causes a hyperphosphorylation of tau protein thus reducing its ability to associate with microtubules inducing cytoskeletal disruption, morphological degeneration and apoptosis indicating that the aberrant activation of tau is neurotoxic.