Distribution, levels, and activity of glycogen synthase kinase-3 in the Alzheimer disease brain.
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.
Pei
J J
JJ
NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
Tanaka
T
T
Tung
Y C
YC
Braak
E
E
Iqbal
K
K
Grundke-Iqbal
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I
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*
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