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

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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

DOI 10.1016/s0306-4522(02)00697-8

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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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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
ORCID: Sun, L
Zhou, X.W
Liu, R
Wang, Q
Wang, J.Z
Venue: Neuroscience
Publisher: Elsevier BV
Published: 2003-06
Volume: 118
Issue: 4
Pages: 1175-1182
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/s0306-4522(02)00697-8
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Pharmacology (medical) › 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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Inhibition of protein phosphatase 2A- and protein phosphatase 1-induced tau hyperphosphorylation and impairment of spatial memory retention in rats

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