Cited by 170Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative Diseases

Inhibition of protein phosphatase 2A- and protein phosphatase 1-induced tau hyperphosphorylation and impairment of spatial memory retention in rats

Sun, L, Liu, S.Y, Zhou, X.W, Wang, X.C, Liu, R, Wang, Q, Wang, J.Z·2003·Neuroscience

Abstract

Tau hyperphosphorylation leads to formation of paired helical filament/neurofibrillary tangles, the hallmark lesion seen in Alzheimer's disease (AD) brain. An imbalanced regulation in protein kinases and protein phosphatases in the affected neurons is proposed to be a reasonable causative factor to the disease process. To verify the hypothesis, we have injected in the present study calyculin A, a potent and specific inhibitor of protein phosphatase (PP) 2A and PP1, into rat hippocampus bilaterally, thus reproduced an Alzheimer's-like deficiency in dephosphorylation system. It was found that calyculin A-injected rats developed lesions in spatial memory retention in Morris water maze test. At mean time, tau was hyperphosphorylated at Ser396/Ser404 (PHF-1) and Ser-262/Ser-356 (12E8) sites determined both by immunohistochemistry and Western blot. It is implicated that (1) PP2A and PP1 participate in the in vivo regulation of tau phosphorylation, and down-regulation of the two phosphatases will result in tau hyperphosphorylation; (2) hyperphosphorylation of tau at PHF-1 and 12E8 sites might be crucial to affect spatial memory in AD.

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Crossref · 10.1016/s0306-4522(02)00697-8

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Authors
Sun, L., Liu, S. Y., Zhou, X. W., Wang, X. C., Liu, R., Wang, Q., & Wang, J. Z.
Affiliations
Huazhong University of Science and Technology (CN)
Corresponding author
Wang, J.Z
Venue
Neuroscience
Publisher
Elsevier BV
Published
2003-06
Volume
118
Issue
4
Pages
1175-1182
ISSN
0306-4522 (ISSN-L)
OpenAlex
W2040147265
Cited by
168
References
56
Citations by year
2026: 5 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 4 · 2020: 8 · 2019: 4 · 2018: 9 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 8 · 2013: 6 · 2012: 9
FWCI
6.13
Type
journal article
Language
en
Open access
closed
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
tau hyperphosphorylation, protein phosphatase 2A, protein phosphatase 1, calyculin A, Alzheimer's disease, spatial memory, hippocampus, neurofibrillary tangles, paired helical filaments, PHF1, protein dephosphorylation, Morris water maze
MeSH terms
Animals, Antibodies, Avoidance Learning, Behavior, Animal, Enzyme Inhibitors, Hippocampus, Immunohistochemistry, Male, Marine Toxins, Oxazoles, Phosphoprotein Phosphatases, Phosphorylation, Spatial Behavior, Swimming, Time Factors, Blotting, Western, tau Proteins, Rats, Sprague-Dawley, Rats, Protein Phosphatase 1, Protein Phosphatase 2

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