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.
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Increased GSK3β expression and CDK5 activity, decreased expression of PP1 and PP2A, and decreased PP2A activity have been observed in specific brain regions in AD patients.
“In support of this, increased GSK3β expression and CDK5 activity, decreased expression of PP1 and PP2A, and decreased PP2A activity has been observed in specific brain regions in AD patients [148–152].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [148]
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- Authors
- PEI, J.-J., TANAKA, T., TUNG, Y.-C., BRAAK, E., IQBAL, K., & GRUNDKE-IQBAL, I.
- Affiliations
- Goethe University Frankfurt (DE)
- ORCID
- IQBAL, KHALID
- Venue
- Journal of Neuropathology and Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 1997-01
- Volume
- 56
- Issue
- 1
- Pages
- 70-78
- ISSN
- 0022-3069 (ISSN-L)
- OpenAlex
- W2047427096
- Cited by
- 371
- References
- 0
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 18 · 2023: 18 · 2022: 11 · 2021: 13 · 2020: 15 · 2019: 11 · 2018: 12 · 2017: 5 · 2016: 12 · 2015: 9 · 2014: 14 · 2013: 15 · 2012: 13
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag008076-09, 5r01ag005892-16, 5r01ns018105-17)
- National Institute on Aging (AG-05892, AG 08076)
- National Institute of Neurological Disorders and Stroke (NS 18105)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- glycogen synthase kinase-3, Alzheimer's disease, tau hyperphosphorylation, neurofibrillary tangles, postsynaptic density, neuronal cell bodies, proline-directed protein kinases, phosphatase activity
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cattle, Cerebral Cortex, Hippocampus, Humans, Nerve Tissue Proteins, Neurons, Phosphoprotein Phosphatases, Phosphorylation, Protein Processing, Post-Translational, Recombinant Proteins, Neurofibrillary Tangles, tau Proteins, Calcium-Calmodulin-Dependent Protein Kinases, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3
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