title: Distribution, levels, and activity of glycogen synthase kinase-3 in the Alzheimer disease brain.
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.
authors.affiliation: NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Pei
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: Y C
authors.initials: YC
authors.lastname: Tung
authors.forename: E
authors.initials: E
authors.lastname: Braak
authors.forename: K
authors.initials: K
authors.lastname: Iqbal
authors.forename: I
authors.initials: I
authors.lastname: Grundke-Iqbal
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002417:Cattle; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000201:enzymology*; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D010749:Phosphoprotein Phosphatases / Q000172:deficiency; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D016875:tau Proteins; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D010749:Phosphoprotein Phosphatases