Hyperphosphorylation of tau and neurofilaments and activation of CDK5 and ERK1/2 in PTEN-deficient cerebella

Mol Cell Neurosci. 2007 Mar;34(3):400-8. doi: 10.1016/j.mcn.2006.11.014. Epub 2007 Jan 5.

Abstract

Inherited mutations to the tumor suppressor PTEN sporadically lead to cerebellar gangliocytoma characterized by migration defects. This has been modeled by CNS-specific PTEN ablation in mice, but the underlying mechanism cannot be explained by the known role of PTEN in Akt/PKB inactivation. Here we show that the loss of PTEN in mouse cerebellar neurons causes neurodegeneration by hyperphosphorylation of tau and neurofilaments, and activation of Cdk5 and pERK1/2, suggesting that dysregulation of the PTEN/pAkt pathway can mediate neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Cell Count
  • Cerebellum / cytology
  • Cerebellum / metabolism*
  • Cyclin-Dependent Kinase 5 / metabolism*
  • Enzyme Activation / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Neurofilament Proteins / metabolism*
  • Neurons / metabolism
  • PTEN Phosphohydrolase / deficiency*
  • Phosphorylation
  • tau Proteins / metabolism*

Substances

  • Neurofilament Proteins
  • tau Proteins
  • Cyclin-Dependent Kinase 5
  • Mitogen-Activated Protein Kinase 3
  • PTEN Phosphohydrolase
  • Pten protein, mouse