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.
authors.affiliation: Department of Neurodegenerative Disease and MRC Prion Unit, Institute of Neurology, University College, London WC1N 3BG, UK.
authors.forename: Naushaba
authors.initials: N
authors.lastname: Nayeem
authors.forename: Fiona
authors.initials: F
authors.lastname: Kerr
authors.forename: Heike
authors.initials: H
authors.lastname: Naumann
authors.forename: Jackie
authors.initials: J
authors.lastname: Linehan
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandner
mesh_terms: 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*
chemical_list: D016900:Neurofilament Proteins; D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; D048052:Mitogen-Activated Protein Kinase 3; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse