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
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Animals, Newborn
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Blotting, Western
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Cell Count
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Cerebellum / cytology
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Cerebellum / metabolism*
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Cyclin-Dependent Kinase 5 / metabolism*
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Enzyme Activation / genetics
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Gene Expression Regulation, Developmental / genetics
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Immunohistochemistry
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinase 3 / metabolism*
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Neurofilament Proteins / metabolism*
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Neurons / metabolism
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PTEN Phosphohydrolase / deficiency*
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Phosphorylation
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tau Proteins / metabolism*
Substances
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Neurofilament Proteins
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tau Proteins
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Cyclin-Dependent Kinase 5
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Mitogen-Activated Protein Kinase 3
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PTEN Phosphohydrolase
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Pten protein, mouse