Cdk5 and Neuregulin-1 Signaling

  • Yi Wen
  • Haung Yu
  • Karen Duff


Cyclin-dependent kinase 5 (cdk5) is implicated in many neurodegenerative diseases including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD). Overexpression of p25 in transgenic mice leads to enhanced cdk5 activity, together with aberrant phosphorylation of cytoskeletal components and the formation of hyperphosphorylated tau. Consistent with previous findings, we observed enhanced NRG-1/ErbB receptor signaling in the p25 overexpressing mice, together with increased PI3 kinase (P13 K)/Akt activity and GSK3β inhibition by S9 phosphorylation. Further, a specific cdk5 inhibitor CP-681301 reduces ErbB2 receptor tyrosine phosphorylation. These results imply that cdk5 is involved in neuregulin-dependent activation of the PI3 K/Akt neuronal survival pathway and potentially other NRG-1-related signaling pathways by regulating the phosphorylation of ErbB2/ErbB3.


Alzheimer Disease Amyotrophic Lateral Sclerosis Cdk5 Activity Susceptibility Candidate Gene Acetylcholine Receptor Cluster 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Pathology, Taub Institute for Alzheimer’s Disease researchColumbia University; NYS Psychiatric InstituteUSA

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