Phosphoprotein Phosphatase Activities in Alzheimer Disease Brain
Abstract
Abstract: Microtubule‐associated protein τ is known to be hyperphosphorylated in Alzheimer disease brain and this abnormal hyperphosphorylation is associated with an inability of τ to promote the assembly of microtubule in the affected neurons. Our previous studies demonstrated that abnormally phosphorylated τ could be dephosphorylated after treatment with alkaline phosphatase, thereby suggesting that the abnormal phosphorylation of τ might in part be the result of a deficiency of the phosphoprotein phosphatase system in patients with Alzheimer disease. In the present study we used 32 P‐labeled phosphorylase kinase and poly(Glu.Tyr) 4:1 as substrates to measure phosphoprotein phosphatase activities in Alzheimer disease and control brains. The activities of phosphoseryl/ phosphothreonyl‐protein phosphatase types 1, 2A, 2B, and 2C and of phosphotyrosyl‐protein phosphatase in frontal gray and white matters from 13 Alzheimer brains were determined and compared with those from 12 age‐matched control brains. The activities of type 1 phosphatase and phosphotyrosyl phosphatase in gray matter and of type 2A phosphatase in both gray and white matters were significantly lower in Alzheimer disease brains than in controls. These findings suggest that the hyperphosphorylation of τ in Alzheimer disease brain could result from a protein dephosphorylation defect in vivo. The decrease in the phosphatase activities in Alzheimer disease might also be involved in the formation of β‐amyloid by augmenting the amyloidogenic pathway processing of β‐amyloid precursor protein.
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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 [152]
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- Authors
- Gong, C., Singh, T. J., Grundke‐Iqbal, I., & Iqbal, K.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1993-09
- Volume
- 61
- Issue
- 3
- Pages
- 921-927
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2148570557
- Cited by
- 527
- References
- 27
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 13 · 2023: 16 · 2022: 20 · 2021: 23 · 2020: 23 · 2019: 12 · 2018: 22 · 2017: 16 · 2016: 11 · 2015: 21 · 2014: 24 · 2013: 21 · 2012: 21
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag008076-09, 5r01ag005892-16)
- National Institute on Aging (AG-05892, AG 08076)
- National Institute of Mental Health (MH.NS 31862)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, protein phosphatase, tau hyperphosphorylation, protein dephosphorylation, protein phosphatase 1, protein phosphatase 2A, calcineurin, protein phosphatase 2C, frontal white matter, amyloid-beta, APP processing, tau protein
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Brain, Brain Chemistry, Female, Humans, Male, Middle Aged, Phosphoprotein Phosphatases, Phosphorylase Kinase, Phosphorylation, Postmortem Changes, Reference Values, Tissue Extracts, Protein Tyrosine Phosphatases, Rats, Sprague-Dawley, Rats, Protein Tyrosine Phosphatase, Non-Receptor Type 1
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