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

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

doi:10.1016/j.mcn.2006.11.014

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

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

Biological and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	400-408
Number of pages	9
Journal	Molecular and Cellular Neuroscience
Volume	34
Issue number	3
DOIs	https://doi.org/10.1016/j.mcn.2006.11.014
Publication status	Published - 5 Jan 2007

Keywords

tau phosphorylation
PTEN
Neurodegeneration

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10.1016/j.mcn.2006.11.014

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title = "Hyperphosphorylation of tau and neurofilaments and activation of CDK5 and ERK1/2 in PTEN-deficient cerebella",

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.",

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author = "Naushaba Nayeem and Fiona Kerr and Heike Naumann and Jackie Linehan and Simon Lovestone and Sebastian Brandner",

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T1 - Hyperphosphorylation of tau and neurofilaments and activation of CDK5 and ERK1/2 in PTEN-deficient cerebella

AU - Nayeem, Naushaba

AU - Kerr, Fiona

AU - Naumann, Heike

AU - Linehan, Jackie

AU - Lovestone, Simon

AU - Brandner, Sebastian

PY - 2007/1/5

Y1 - 2007/1/5

N2 - 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.

AB - 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.

KW - tau phosphorylation

KW - PTEN

KW - Neurodegeneration

U2 - 10.1016/j.mcn.2006.11.014

DO - 10.1016/j.mcn.2006.11.014

M3 - Article

VL - 34

SP - 400

EP - 408

JO - Molecular and Cellular Neuroscience

JF - Molecular and Cellular Neuroscience

SN - 1044-7431

IS - 3

ER -