Hyperphosphorylation of tau and neurofilaments and activation of CDK5 and ERK1/2 in PTEN-deficient cerebella.
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.
Nayeem
Naushaba
N
Department of Neurodegenerative Disease and MRC Prion Unit, Institute of Neurology, University College, London WC1N 3BG, UK.
Kerr
Fiona
F
Naumann
Heike
H
Linehan
Jackie
J
Lovestone
Simon
S
Brandner
Sebastian
S
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002452:Cell Count; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D004789:Enzyme Activation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000172:deficiency*; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
D016900:Neurofilament Proteins; D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; D048052:Mitogen-Activated Protein Kinase 3; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse