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: J J Pei, T Tanaka, Y C Tung, E Braak, K Iqbal, I Grundke-Iqbal
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 56 Issue 1 Pg. 70-8 (Jan 1997) ISSN: 0022-3069 [Print] England
• PMID: 8990130 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Nerve Tissue Proteins
• Recombinant Proteins
• tau Proteins
• Glycogen Synthase Kinases
• Calcium-Calmodulin-Dependent Protein Kinases
• Glycogen Synthase Kinase 3
• Phosphoprotein Phosphatases

Topics

• Alzheimer Disease (enzymology, pathology)
• Animals
• Brain (enzymology, pathology)
• Calcium-Calmodulin-Dependent Protein Kinases (metabolism)
• Cattle
• Cerebral Cortex (enzymology, pathology)
• Glycogen Synthase Kinase 3
• Glycogen Synthase Kinases
• Hippocampus (enzymology, pathology)
• Humans
• Nerve Tissue Proteins (metabolism)
• Neurofibrillary Tangles (enzymology)
• Neurons (enzymology, pathology)
• Phosphoprotein Phosphatases (deficiency)
• Phosphorylation
• Protein Processing, Post-Translational
• Recombinant Proteins (metabolism)
• tau Proteins (genetics, metabolism)