Abstract
A number of studies have implicated a proline-directed protein kinase, glycogen synthase kinase-3 (GSK-3) in the hyperphosphorylation of tau in Alzheimer's disease (AD). Toward understanding the role of GSK-3 in the abnormal hyperphosphorylation of tau in AD we have found that GSK-3 is prominently present in neuronal cell bodies and their processes and co-localizes with neurofibrillary changes in AD brain. Furthermore, the levels of GSK-3 as determined by indirect ELISA are approximately 50% increased in the postsynaptosomal supernatant from AD brains as compared to the controls. However, no increase in GSK-3 enzyme activity was detected. In AD brain, with its reduced phosphatase activity, even normal levels of GSK-3 activity might be sufficient for the hyperphosphorylation of tau.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alzheimer Disease / enzymology*
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Alzheimer Disease / pathology
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Animals
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Brain / enzymology*
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Brain / pathology
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cattle
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Cerebral Cortex / enzymology
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Cerebral Cortex / pathology
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Glycogen Synthase Kinase 3
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Glycogen Synthase Kinases
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Hippocampus / enzymology
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Hippocampus / pathology
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Humans
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Nerve Tissue Proteins / metabolism*
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Neurofibrillary Tangles / enzymology*
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Neurons / enzymology
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Neurons / pathology
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Phosphoprotein Phosphatases / deficiency
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Phosphorylation
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Protein Processing, Post-Translational
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Recombinant Proteins / metabolism
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tau Proteins / genetics
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tau Proteins / metabolism*
Substances
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Nerve Tissue Proteins
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Recombinant Proteins
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tau Proteins
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Glycogen Synthase Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3
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Phosphoprotein Phosphatases