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

Nayeem, Naushaba; Kerr, Fiona; Naumann, Heike; Linehan, Jackie; Lovestone, Simon; Brandner, Sebastian

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.

Citation

Nayeem, N., Kerr, F., Naumann, H., Linehan, J., Lovestone, S., & Brandner, S. (2007). Hyperphosphorylation of tau and neurofilaments and activation of CDK5 and ERK1/2 in PTEN-deficient cerebella. Molecular and Cellular Neuroscience, 34(3), 400-408. https://doi.org/10.1016/j.mcn.2006.11.014

• Journal Article Type: Article
• Acceptance Date: Nov 15, 2006
• Online Publication Date: Jan 5, 2007
• Publication Date: 2007-03
• Deposit Date: Aug 19, 2016
• Journal: Molecular and Cellular Neuroscience
• Print ISSN: 1044-7431
• Electronic ISSN: 1044-7431
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 34
• Issue: 3
• Pages: 400-408
• DOI: https://doi.org/10.1016/j.mcn.2006.11.014
• Keywords: Tau phosphorylation; PTEN; Cre-LoxP system; Transgenic mice; Neurodegeneration
• Public URL: http://researchrepository.napier.ac.uk/Output/355836