Inhibition of protein phosphatase 2A- and protein phosphatase 1-induced tau hyperphosphorylation and impairment of spatial memory retention in rats
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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Inhibition of PP2A in cultured brain slices and rat brains induced tau hyperphosphorylation at multiple sites known to be related to AD.
“Inhibition of PP2A in cultured brain slices and rat brains induced tau hyperphosphorylation at multiple sites known to be related to AD (Gong et al., 2000; Sun et al., 2003).”
From CIP2A Causes Tau/APP Phosphorylation, Synaptopathy, and Memory Deficits in Alzheimer’s Disease (2018) · cites this paper as Sun et al., 2003
Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · see citing works
(1982) · Trends in Neurosciences · doi:10.1016/0166-2236(82)90076-5 · Cited by 9,148 · see citing works
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668 · see citing works
Bourtchuladze, R., Frenguelli, B., Blendy, J., Cioffi, D., Schutz, G., & Silva, A. J. (1994) · Cell · doi:10.1016/0092-8674(94)90400-6 · Cited by 1,800 · see citing works
Microtubule-associated protein tau. A component of Alzheimer paired helical filaments.
Grundke, I., Iqbal, K., Quinlan, M., Tung, Y. C., Zaidi, M. S., & Wisniewski, H. M. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38495-8 · Cited by 1,780 · see citing works
Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP
Lewis, J., Dickson, D. W., Lin, W.-L., Chisholm, L., Corral, A., Jones, G., Yen, S.-H., Sahara, N., Skipper, L., Yager, D., et al. (2001) · Science · doi:10.1126/science.1058189 · Cited by 1,611 · see citing works
Formation of Neurofibrillary Tangles in P301L Tau Transgenic Mice Induced by Aβ42 Fibrils
Götz, J., Chen, F., van Dorpe, J., & Nitsch, R. M. (2001) · Science · doi:10.1126/science.1062097 · Cited by 1,526 · see citing works
A68: a Major Subunit of Paired Helical Filaments and Derivatized Forms of Normal Tau
Lee, V. M.-Y., Balin, B. J., Otvos, L., & Trojanowski, J. Q. (1991) · Science · doi:10.1126/science.1899488 · Cited by 1,418 · see citing works
Lewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Murphy, M. P., Baker, M., Yu, X., et al. (2000) · Nature Genetics · doi:10.1038/78078 · Cited by 1,371 · see citing works
Goedert, M., Spillantini, M. G., Cairns, N. J., & Crowther, R. A. (1992) · Neuron · doi:10.1016/0896-6273(92)90117-v · Cited by 1,114 · see citing works
Involvement of a calcineurin/ inhibitor-1 phosphatase cascade in hippocampal long-term depression
Mulkey, R. M., Endo, S., Shenolikar, S., & Malenka, R. C. (1994) · Nature · doi:10.1038/369486a0 · Cited by 1,083 · see citing works
Pearson, R. C., Esiri, M. M., Hiorns, R. W., Wilcock, G. K., & Powell, T. P. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.13.4531 · Cited by 987 · see citing works
Bancher, C., Brunner, C., Lassmann, H., Budka, H., Jellinger, K., Wiche, G., Seitelberger, F., Grundke-Iqbal, I., Iqbal, K., & Wisniewski, H. M. (1989) · Brain Research · doi:10.1016/0006-8993(89)91396-6 · Cited by 818 · see citing works
Köpke, E., Tung, Y. C., Shaikh, S., Alonso, A. C., Iqbal, K., & Grundke-Iqbal, I. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)80536-5 · Cited by 779 · see citing works
Tau protein function in living cells.
Drubin, D. G., & Kirschner, M. W. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.103.6.2739 · Cited by 745 · see citing works
An Essential Role for Protein Phosphatases in Hippocampal Long-Term Depression
Mulkey, R. M., Herron, C. E., & Malenka, R. C. (1993) · Science · doi:10.1126/science.8394601 · Cited by 699 · see citing works
Phosphoprotein Phosphatase Activities in Alzheimer Disease Brain
Gong, C., Singh, T. J., Grundke‐Iqbal, I., & Iqbal, K. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03603.x · Cited by 527 · see citing works
Monoclonal antibody PHF‐1 recognizes tau protein phosphorylated at serine residues 396 and 404
Otvos, L., Feiner, L., Lang, E., Szendrei, G. I., Goedert, M., & Lee, V. M. (1994) · Journal of Neuroscience Research · doi:10.1002/jnr.490390607 · Cited by 488 · see citing works
Paxinos, G., WATSON, C. R. R., Pennisi, M., & Topple, A. N. (1985) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(85)90026-3 · Cited by 483 · see citing works
Guzowski, J. F., & McGaugh, J. L. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.6.2693 · Cited by 481 · see citing works
Gong, C.-X., Lidsky, T., Wegiel, J., Zuck, L., Grundke-Iqbal, I., & Iqbal, K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.8.5535 · Cited by 405 · see citing works
Detection of Phosphorylated Ser262 in Fetal Tau, Adult Tau, and Paired Helical Filament Tau
Seubert, P., Mawal-Dewan, M., Barbour, R., Jakes, R., Goedert, M., Johnson, G. V. W., Litersky, J. M., Schenk, D., Lieberburg, I., Trojanowski, J. Q., et al. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.32.18917 · Cited by 345 · see citing works
Molecular Interactions among Protein Phosphatase 2A, Tau, and Microtubules
Sontag, E., Nunbhakdi‐Craig, V., Lee, G. S., Brandt, R., Kamibayashi, C., Kuret, J., White, C. L., Mumby, M. C., & Bloom, G. S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.36.25490 · Cited by 305 · see citing works
Illenberger, S., Zheng‐Fischhöfer, Q., Preuß, U., Stamer, K., Baumann, K., Trinczek, B., Biernat, J., Godemann, R., Mandelkow, E., & Mandelkow�, E. (1998) · Molecular Biology of the Cell · doi:10.1091/mbc.9.6.1495 · Cited by 300 · see citing works
Favre, B., Turowski, P., & Hemmings, B. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.21.13856 · Cited by 300 · see citing works
Microtubule-Associated Protein Tau
Yen, S.-H. C., Nacharaju, P., Ko, L., Kenessey, Á., & Liu, W.-K. (1998) · Elsevier eBooks · doi:10.1016/b978-012734610-6/50012-9 · Cited by 284 · see citing works
PP2A mRNA Expression Is Quantitatively Decreased in Alzheimer's Disease Hippocampus
Vogelsberg-Ragaglia, V., Schuck, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2001) · Experimental Neurology · doi:10.1006/exnr.2001.7630 · Cited by 281 · see citing works
Neurodegenerative disorders with extensive tau pathology: A comparative study and review
Feany, M. Β., & Dickson, D. W. (1996) · Annals of Neurology · doi:10.1002/ana.410400204 · Cited by 279 · see citing works
Wilensky, A. E., Schafe, G. E., & LeDoux, J. E. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-18-07059.2000 · Cited by 265 · see citing works
Kins, S., Crameri, A., Evans, D. R. H., Hemmings, B. A., Nitsch, R. M., & Götz, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102621200 · Cited by 203 · see citing works
Fetal‐Type Phosphorylation of the τ in Paired Helical Filaments
Kanemaru, K., Takio, K., Miura, R., Titani, K., & Ihara, Y. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb10039.x · Cited by 197 · see citing works
Planel, E., Yasutake, K., Fujita, S. C., & Ishiguro, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102780200 · Cited by 197 · see citing works
Bennecib, M., Gong, C.-X., Grundke-Iqbal, I., & Iqbal, K. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)02203-1 · Cited by 184 · see citing works
Wang, J., Grundke, I., & Iqbal, K. (1996) · Molecular Brain Research · doi:10.1016/0169-328x(95)00316-k · Cited by 154 · see citing works
Self-citationProtein Phosphatase 1 Is Targeted to Microtubules by the Microtubule-associated Protein Tau
Liao, H., Li, Y., Brautigan, D. L., & Gundersen, G. G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.34.21901 · Cited by 145 · see citing works
Merrick, S. E., Trojanowski, J. Q., & Lee, V. M.-Y. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-15-05726.1997 · Cited by 143 · see citing works
Arendt, T., Holzer, M., Fruth, R., Brückner, M. K., & Gärtner, U. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00347-l · Cited by 132 · see citing works
Léger, J. G., Kempf, M., Lee, G. S., & Brandt, R. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.13.8441 · Cited by 131 · see citing works
The regulation of phosphorylation of τ in SY5Y neuroblastoma cells: the role of protein phosphatases
Tanaka, T., Zhong, J., Iqbal, K., Trenkner, E., & Grundke, I. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00346-9 · Cited by 113 · see citing works
Hasegawa, M., Watanabe, A., Takio, K., Suzuki, M., Arai, T., Titani, K., & Ihara, Y. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03491.x · Cited by 105 · see citing works
Phosphorylation of Tau, Aβ-Formation, and Apoptosis After In Vivo Inhibition of PP-1 and PP-2A
Arendt, T., Holzer, M., Fruth, R., Brückner, M. K., & Gärtner, U. (1998) · Neurobiology of Aging · doi:10.1016/s0197-4580(98)00003-7 · Cited by 88 · see citing works
Gong, C., Węgiel, J., Lidsky, T. I., Zuck, L., Ávila, J., Wı́sniewski, H. M., Grundke, I., & Iqbal, K. (2000) · Brain Research · doi:10.1016/s0006-8993(99)02294-5 · Cited by 81 · see citing works
Merrick, S. E., Demoise, D. C., & Lee, V. M. ‐. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.10.5589 · Cited by 81 · see citing works
Kim, D., Su, J. H., & Cotman, C. W. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01724-2 · Cited by 70 · see citing works
Liu, W.-K., Moore, W. T., Williams, R., Hall, F. L., & Yen, S. (1993) · Journal of Neuroscience Research · doi:10.1002/jnr.490340315 · Cited by 69 · see citing works
Thiels, E., Kanterewicz, B. I., Knapp, L. T., Barrionuevo, G., & Klann, E. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-19-07199.2000 · Cited by 65 · see citing works
Spared retention of inhibitory avoidance learning after posttraining amygdala lesions.
Parent, M. B., Quirarte, G. L., Cahill, L. F., & McGaugh, J. L. (1995) · Behavioral Neuroscience · doi:10.1037//0735-7044.109.4.803 · Cited by 60 · see citing works
On how passive is inhibitory avoidance
Netto, C. A., & Izquierdo, I. (1985) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(85)91697-8 · Cited by 51 · see citing works
He, J., Yamada, K., Zou, L. B., & Nabeshima, T. (2001) · Journal of Neural Transmission · doi:10.1007/s007020100018 · Cited by 49 · see citing works
Spared retention of inhibitory avoidance learning after posttraining amygdala lesions.
Parent, M. B., Quirarte, G. L., Cahill, L. F., et al. (1995) · Behavioral Neuroscience · doi:10.1037/0735-7044.109.4.803 · Cited by 49 · see citing works
Yamamoto, H., Hasegawa, M., Ono, T., Tashima, K., Ihara, Y., & Miyamoto, E. (1995) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a125011 · Cited by 42 · see citing works
Molecular cloning of Fyn-associated molecules in the mouse central nervous system
Kai, N., Mishina, M., & Yagi, T. (1997) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19970601)48:5 · Cited by 37 · see citing works
MICROTUBULE ASSOCIATED PROTEIN TAU
Iqbal, K., Grundke‐Iqbal, I., & Smith, A. (1989) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-198905000-00164 · Cited by 35 · see citing works
Gong, C., Lidsky, T. I., Węgiel, J., Grundke, I., & Iqbal, K. (2001) · Brain Research Protocols · doi:10.1016/s1385-299x(00)00046-5 · Cited by 35 · see citing works
Lee, J.-H., Hong, H., Im, J.-O., Byun, H.-S., & Kim, D. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)00863-6 · Cited by 29 · see citing works
Bennett, P. C., Zhao, W., & Ng, K. T. (2001) · Neurobiology of Learning and Memory · doi:10.1006/nlme.1999.3959 · Cited by 26 · see citing works
Mudher, A. K., WOOLLEY, S. T., Perry, V. H., & Greene, J. R. T. (1999) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(99)00006-0 · Cited by 8 · see citing works
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Ramsden, M., Kotilinek, L., Forster, C., Paulson, J., McGowan, E., SantaCruz, K., Guimaraes, A., Yue, M., Lewis, J., Carlson, G., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3279-05.2005 · Cited by 702 · see citing works
Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration
Wang, J., Grundke, I., & Iqbal, K. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05226.x · Cited by 553 · see citing works
Self-citationWang, J., Xia, Y., Grundke, I., & Iqbal, K. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-129031 · Cited by 532 · see citing works
Self-citationThe role of tau in neurodegeneration
Gendron, T. F., & Petrucelli, L. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-13 · Cited by 478 · see citing works
Microtubule-associated protein tau in development, degeneration and protection of neurons
Wang, J., & Liu, F. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.03.002 · Cited by 395 · see citing works
Self-citationProtein phosphatase 2A dysfunction in Alzheimer’s disease
Sontag, J.-M., & Sontag, E. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00016 · Cited by 304 · see citing works
Ferrer, I., Gómez‐Isla, T., Puig, B., Freixes, M., Ribé, E. M., Dalfó, E., & Ávila, J. (2005) · Current Alzheimer Research · doi:10.2174/1567205052772713 · Cited by 302 · see citing works
Tau-Targeted Multifunctional Nanocomposite for Combinational Therapy of Alzheimer’s Disease
Chen, Q., Du, Y., Zhang, K., Liang, Z., Li, J., Yu, H., Ren, R., Feng, J., Jin, Z., Li, F., et al. (2018) · ACS Nano · doi:10.1021/acsnano.7b07625 · Cited by 280 · see citing works
Dickey, C. A., Yue, M., Lin, W.-L., Dickson, D. W., Dunmore, J. H., Lee, W. C., Zehr, C., West, G., Cao, S., Clark, A. M. K., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0746-06.2006 · Cited by 248 · see citing works
Tau protein phosphatases in Alzheimer's disease: The leading role of PP2A
Martin, L., Latypova, X., Wilson, C. M., Magnaudeix, A., Perrin, M.-L., & Terro, F. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.06.008 · Cited by 249 · see citing works
The links between axin and carcinogenesis
Salahshor, S., & Woodgett, J. R. (2005) · Journal of Clinical Pathology · doi:10.1136/jcp.2003.009506 · Cited by 250 · see citing works
Gupta, S., Franklin, A. V., DeRamus, T. P., Wheelock, M. D., Davis, R. L., McMahon, L. L., & Lubin, F. D. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0147-12.2012 · Cited by 224 · see citing works
Up-regulation of inhibitors of protein phosphatase-2A in Alzheimer’s disease
Tanimukai, H., Grundke-Iqbal, I., & Iqbal, K. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)62486-8 · Cited by 220 · see citing works
Shimura, H., Miura-Shimura, Y., & Kosik, K. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400351200 · Cited by 194 · see citing works
Dickey, C. A., Dunmore, J., Lu, B., Wang, J., Lee, W. C., Kamal, A., Burrows, F., Eckman, C., Hutton, M., & Petrucelli, L. (2006) · The FASEB Journal · doi:10.1096/fj.05-5343fje · Cited by 160 · see citing works
Self-citationHomocysteine induces tau phosphorylation by inactivating protein phosphatase 2A in rat hippocampus
Zhang, C.-E., Tian, Q., Wei, W., Peng, J.-H., Liu, G., Zhou, X., Wang, Q., Wang, D. W., & Wang, J. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.04.015 · Cited by 159 · see citing works
Self-citationProtein serine/threonine phosphatases in neuronal plasticity and disorders of learning and memory
Mansuy, I. M., & Shenolikar, S. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.10.004 · Cited by 151 · see citing works
Betaine attenuates Alzheimer‐like pathological changes and memory deficits induced by homocysteine
Chai, G., Jiang, X., Ni, Z.-F., Ma, Z., Xie, A., Cheng, X., Wang, Q., Wang, J., & Liu, G. (2012) · Journal of Neurochemistry · doi:10.1111/jnc.12094 · Cited by 144 · see citing works
Self-citationTau-Based Treatment Strategies in Neurodegenerative Diseases
Schneider, A., & Mandelkow�, E. (2008) · Neurotherapeutics · doi:10.1016/j.nurt.2008.05.006 · Cited by 142 · see citing works
Derry, P. J., Hegde, M. L., Jackson, G. R., Kayed, R., Tour, J. M., Tsai, A.-L., & Kent, T. A. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101716 · Cited by 142 · see citing works
Strategies for the Inhibition of Protein Aggregation in Human Diseases
Bartolini, M., & Andrisano, V. (2010) · ChemBioChem · doi:10.1002/cbic.200900666 · Cited by 136 · see citing works
Moderate noise induced cognition impairment of mice and its underlying mechanisms
Cheng, L., Wang, S., Chen, Q.-C., & Liao, X. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.06.018 · Cited by 135 · see citing works
Cross talk between PI3K-AKT-GSK-3β and PP2A pathways determines tau hyperphosphorylation
Wang, Y., Yang, R., Gu, J., Yin, X., Jin, N., Xie, S., Wang, Y., Chang, H., Qian, W., Shi, J., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.07.035 · Cited by 134 · see citing works
Phosphorylated tau and the neurodegenerative foldopathies
Kosik, K. S., & Shimura, H. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.10.011 · Cited by 123 · see citing works
Phosphoprotein Phosphatase 2A: A Novel Druggable Target for Alzheimer’s Disease
Voronkov, M. V., Braithwaite, S. P., & Stock, J. B. (2011) · Future Medicinal Chemistry · doi:10.4155/fmc.11.47 · Cited by 121 · see citing works
Involvement of in the abnormal hyperphosphorylation of tau and its reversal by Memantine
Chohan, M. O., Khatoon, S., Iqbal, I.-G., & Iqbal, K. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.06.021 · Cited by 120 · see citing works
Kamat, P. K., Rai, S., Swarnkar, S., Shukla, R., & Nath, C. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8699-4 · Cited by 112 · see citing works
Song, X., Hu, J.-F., Chu, S., Zhang, Z., Xu, S., Yuan, Y., Han, N., Liu, Y., Niu, F., He, X., et al. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.03.051 · Cited by 107 · see citing works
Siddiqi, K. S., Husen, A., Sohrab, S. S., & Yassin, M. O. (2018) · Nanoscale Research Letters · doi:10.1186/s11671-018-2638-7 · Cited by 103 · see citing works
The role of protein phosphatase-1 in the modulation of synaptic and structural plasticity
Munton, R. P., Vizi, S., & Mansuy, I. M. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.03.121 · Cited by 96 · see citing works
CIP2A Causes Tau/APP Phosphorylation, Synaptopathy, and Memory Deficits in Alzheimer’s Disease
Shentu, Y.-P., Huo, Y., Feng, X.-L., Gilbert, J., Zhang, Q., Liuyang, Z.-Y., Wang, X.-L., Wang, G., Zhou, H., Wang, X.-C., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.009 · Cited by 90 · see citing works
“Inhibition of PP2A in cultured brain slices and rat brains induced tau hyperphosphorylation at multiple sites known to be related to AD (Gong et al., 2000; Sun et al., 2003).”
BackgroundSelf-citationA Proteomic Analysis of MCLR-induced Neurotoxicity: Implications for Alzheimer's Disease
Li, G., Cai, F., Yan, W., Li, C., & Wang, J. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs114 · Cited by 90 · see citing works
Self-citationRifaai, R., Mokhemer, S., Saber, E., El-Aleem, S. A., & El-Tahawy, N. (2020) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2020.101795 · Cited by 80 · see citing works
Zhao, J., Yin, F., Ji, L., Wang, C., Shi, C., Liu, X., Yang, H., Wang, X., & Kong, L. (2020) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.0c11064 · Cited by 87 · see citing works
Self-citationDickey, C. A., Kraft, C., Jinwal, U. K., Koren, J., Johnson, A. G., Anderson, L. C., Lebson, L. A., Lee, D. C., Dickson, D. W., de Silva, R., et al. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2009.080764 · Cited by 85 · see citing works
Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?
Munday, R. (2013) · Toxins · doi:10.3390/toxins5020267 · Cited by 85 · see citing works
Coenzyme Q10 Reduces β-Amyloid Plaque in an APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease
Yang, X., Dai, G., Li, G., & Yang, E. S. (2009) · Journal of Molecular Neuroscience · doi:10.1007/s12031-009-9297-1 · Cited by 83 · see citing works
Wang, X., Blanchard, J., Kohlbrenner, E., Clement, N., Linden, R. M., Radu, A., Grundke, I., & Iqbal, K. (2010) · The FASEB Journal · doi:10.1096/fj.10-158477 · Cited by 81 · see citing works
Self-citationAn okadaic acid-induced model of tauopathy and cognitive deficiency
Zhang, Z., & Simpkins, J. W. (2010) · Brain Research · doi:10.1016/j.brainres.2010.08.077 · Cited by 81 · see citing works
Protein Phosphatase 2A Facilitates Axonogenesis by Dephosphorylating CRMP2
Zhu, L., Zheng, H., Peng, C., Liu, D., Li, H., Wang, Q., & Wang, J. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5174-09.2010 · Cited by 80 · see citing works
Self-citationRı́os, C. D. L., Egea, J., Marco, J. L., Leon, R. M., Samadi, A., Iriepa, I., Moraleda, I., Galvez‐Ruano, E., Garcı́a, A. G., López, M. G., et al. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm901902w · Cited by 79 · see citing works
Hashimoto, M., Shahdat, H. M., Yamashita, S., Katakura, M., Tanabe, Y., Fujiwara, H., Gamoh, S., Miyazawa, T., Arai, H., Shimada, T., et al. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05731.x · Cited by 80 · see citing works
Protective effects of chondroitin sulphate nano-selenium on a mouse model of Alzheimer's disease
Ji, D., Wu, X., Li, D., Liu, P., Zhang, S., Gao, D., Gao, F., Zhang, M., & Xiao, Y. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.03.079 · Cited by 75 · see citing works
Zhu, L., Wang, S. H., Ling, Z.-Q., Wang, D. L., & Wang, J. (2004) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2004.00136.x · Cited by 74 · see citing works
Self-citationWang, J., Wang, Z.-H., & Tian, Q. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1415-y · Cited by 74 · see citing works
Self-citationKang, E., & Cho, J.-Y. (2015) · Physical Activity and Nutrition · doi:10.5717/jenb.2015.15090806 · Cited by 75 · see citing works
Falluel‐Morel, A., Vaudry, D., Aubert, N., Galas, L., Bénard, M., Basille, M., Fontaine, M., Fournier, A., Vaudry, H., & Gonzalez, B. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409681102 · Cited by 72 · see citing works
Hypoxia-Induced Tau Phosphorylation and Memory Deficit in Rats
Zhang, C.-E., Yang, X., Li, L., Sui, X., Tian, Q., Wei, W., Wang, J., & Liu, G. (2014) · Neurodegenerative Diseases · doi:10.1159/000362239 · Cited by 70 · see citing works
Self-citationBalmik, A. A., & Chinnathambi, S. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170900 · Cited by 69 · see citing works
Domenico, F. D., Tramutola, A., Barone, E., Lanzillotta, C., Defever, O., Arena, A., Zuliani, I., Foppoli, C., Iavarone, F., Vincenzoni, F., et al. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101162 · Cited by 69 · see citing works
Effect of melatonin on calyculin A-induced tau hyperphosphorylation
Li, X., Wang, X., Zhang, J., Wang, Q., & Wang, J. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.01.023 · Cited by 68 · see citing works
Self-citationKhalil, A. T., Ayaz, M., Ovais, M., Wadood, A., Ali, M., Shinwari, Z. K., & Mâaza, M. (2018) · Inorganic and Nano-Metal Chemistry · doi:10.1080/24701556.2019.1569686 · Cited by 66 · see citing works
Neurotherapeutic applications of nanomedicine for treating Alzheimer's disease
Wilson, B., & Geetha, K. M. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.05.044 · Cited by 65 · see citing works
Nanoparticle-mediated growth factor delivery systems: A new way to treat Alzheimer's disease
Lauzon, M.-A., Daviau, A., Marcos, B., & Faucheux, N. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.03.024 · Cited by 65 · see citing works
Qu, L., Li, S., Ji, L., Luo, S., Ding, M., Yin, F., Wang, C., Luo, H., Lu, D., Liu, X., et al. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113889 · Cited by 61 · see citing works
Self-citationBiomaterials for the Treatment of Alzheimer’s Disease
Hadavi, D., & Poot, A. A. (2016) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2016.00049 · Cited by 61 · see citing works
Ling, Z.-Q., Tian, Q., Wang, L., Fu, Z., Wang, X., Wang, Q., & Wang, J. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-0949 · Cited by 60 · see citing works
Self-citationYang, X., Yang, Y., Fu, Z., Li, Y., Feng, J. B., Luo, J., Zhang, Q., Wang, Q., & Tian, Q. (2010) · Journal of Psychopharmacology · doi:10.1177/0269881110367723 · Cited by 58 · see citing works
Self-citationTian, Q., Lin, Z.-Q., Wang, X., Chen, J., Wang, Q., Gong, C., & Wang, J. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.03.037 · Cited by 57 · see citing works
Self-citationMechanisms for Cognitive Impairment in Epilepsy: Moving Beyond Seizures
Khalife, M. R., Scott, R. C., & Hernan, A. E. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.878991 · Cited by 56 · see citing works
Effects of tau phosphorylation on proteasome activity
Ren, Q., Liao, X., Chen, X., Liu, G., & Wang, J. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.02.065 · Cited by 54 · see citing works
Self-citationBusceti, C. L., Biagioni, F., Riozzi, B., Battaglia, G., Storto, M., Cinque, C., Molinaro, G., Gradini, R., Caricasole, A., Canudas, A. M., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0159-08.2008 · Cited by 51 · see citing works
Protein phosphatase 2A in Alzheimer's disease
Liu, R., & Wang, J. (2009) · Pathophysiology · doi:10.1016/j.pathophys.2009.02.008 · Cited by 50 · see citing works
Self-citationRole of protein phosphatases and mitochondria in the neuroprotective effects of estrogens
Simpkins, J. W., Yi, K. D., & Yang, S. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.04.013 · Cited by 48 · see citing works
Sun, W., Ban, J., Zhang, N., Zu, Y., & Sun, W. (2012) · Environmental Toxicology · doi:10.1002/tox.21785 · Cited by 46 · see citing works
Nanomedicines in the Management of Alzheimer’s Disease: Current View and Future Prospects
Chopra, H., Bibi, S., Singh, I., Kamal, M. A., Islam, F., Alhumaydhi, F. A., Emran, T. B., & Cavalu, S. D. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.879114 · Cited by 47 · see citing works
Liang, Z., Liu, F., Iqbal, K., Grundke, I., Węgiel, J., & Gong, C. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-13307 · Cited by 43 · see citing works
Zhou, P., Chen, Z., Zhao, N., Liu, D., Guo, Z., Tan, L., Hu, J., Wang, Q., Wang, J., & Zhu, L. (2011) · Rejuvenation Research · doi:10.1089/rej.2011.1195 · Cited by 42 · see citing works
Self-citationZhang, Y., Tian, Q., Zhang, Q., Zhou, X., Liu, S., & Wang, J. (2009) · Pathophysiology · doi:10.1016/j.pathophys.2009.02.003 · Cited by 42 · see citing works
Self-citationOkadaic acid increases autophagosomes in rat neurons: Implications for Alzheimer's disease
Yoon, S. Y., Choi, J. E., Kweon, H., Choe, H., Kim, S. W., Hwang, O., Lee, H., Lee, J., & Kim, D. H. (2008) · Journal of Neuroscience Research · doi:10.1002/jnr.21760 · Cited by 40 · see citing works
Shen, X., Luo, T., Li, S., Ting, O., He, F., Xu, J., & Wang, H. (2017) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2017.3281 · Cited by 40 · see citing works
Yoon, S. Y., Choi, J. E., Yoon, J. H., Huh, J., & Kim, D. H. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.12.013 · Cited by 39 · see citing works
Falluel‐Morel, A., Chafaï, M., Vaudry, D., Basille, M., Cazillis, M., Aubert, N., Louiset, E., DeJouffrey, S., Bigot, J., Fournier, A., et al. (2007) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01537.x · Cited by 39 · see citing works
Cho, M.-H., Kim, D., Choi, J., Chang, E., & Seung-YongYoon (2012) · Brain Research · doi:10.1016/j.brainres.2012.03.010 · Cited by 38 · see citing works
Impairment of spatial learning and memory in ELKL Motif Kinase1 (EMK1/MARK2) knockout mice
Ségu, L., Pascaud, A., Costet, P., Darmon, M. Y., & Buhot, M.-C. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.10.014 · Cited by 39 · see citing works
Inhibition of protein phosphatases induces transport deficits and axonopathy
Yang, Y., Yang, X., Wang, Y., Tian, Q., Wang, X., Li, H., Wang, Q., & Wang, J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04603.x · Cited by 37 · see citing works
Self-citationDeng, J., Shen, C., Wang, Y., Zhang, M., Li, J., Xu, Z., Gao, C., Fang, C., & Zhou, H. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.03.029 · Cited by 36 · see citing works
Liu, G., Wei, W., Zhou, X., Shi, H.-R., Liu, X.-H., Chai, G., Yao, X., Zhang, J. Y., Peng, C., Hu, J., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2013.189 · Cited by 35 · see citing works
Self-citationChao, C.-C., Ma, Y., & Lee, E. H. Y. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1531-07.2007 · Cited by 35 · see citing works
Berberine Attenuates Axonal Transport Impairment and Axonopathy Induced by Calyculin A in N2a Cells
Liu, X., Zhou, J., Abid, M. D. N., Yan, H., Huang, H., Wan, L., Feng, Z., & Chen, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093974 · Cited by 34 · see citing works
The role of post‐translational modifications for learning and memory formation
Sunyer, B., Diao, W., & Lübec, G. (2008) · Electrophoresis · doi:10.1002/elps.200700791 · Cited by 34 · see citing works
Orejana, L., Barros-Miñones, L., Aguirre, N., & Puerta, E. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.03.001 · Cited by 32 · see citing works
Casein Kinase 1 and Human Disease: Insights From the Circadian Phosphoswitch
Francisco, J. C., & Virshup, D. M. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.911764 · Cited by 29 · see citing works
Liu, R., Pei, J.-J., Wang, X., Zhou, X., Tian, Q., Winblad, B. G., & Wang, J. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03270.x · Cited by 31 · see citing works
Self-citationLajarín-Cuesta, R., Nanclares, C., Arranz-Tagarro, J.-A., González‐Lafuente, L., Arribas, R. L., de Brito, M. A., Gandı́a, L., & Rı́os, C. D. L. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00478 · Cited by 30 · see citing works
Growth factor treatment to overcome Alzheimer's dysfunctional signaling
Lauzon, M.-A., Daviau, A., Marcos, B., & Faucheux, N. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.02.018 · Cited by 30 · see citing works
Amyloid-β as a biomarker for Alzheimer’s disease: quantification methods in body fluids
Galozzi, S., Marcus, K., & Barkovits, K. (2015) · Expert Review of Proteomics · doi:10.1586/14789450.2015.1065183 · Cited by 30 · see citing works
Liu, B., Sun, L.-H., Huang, Y.-F., Guo, L.-J., & Luo, L.-S. (2018) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2017.12.015 · Cited by 29 · see citing works
Self-citationBusceti, C. L., Pietro, P. D., Riozzi, B., Traficante, A., Biagioni, F., Nisticò, R., Fornai, F., Battaglia, G., Nicoletti, F., & Bruno, V. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.06.017 · Cited by 29 · see citing works
Salissou, M. T. M., Mahaman, Y. A. R., Zhu, F., Huang, F., Wang, Y., Xu, Z., Ke, D., Wang, Q., Liu, R., Wang, J., et al. (2018) · Aging · doi:10.18632/aging.101627 · Cited by 29 · see citing works
Self-citationZüchner, T., Schliebs, R., & Perez-Polo, J. R. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03335.x · Cited by 29 · see citing works
Asam, K. R., Staniszewski, A., Zhang, H., Melideo, S. L., Mazzeo, A., Voronkov, M. V., Huber, K. L., Pérez, E., Stock, M. B., Stock, J. B., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0189413 · Cited by 28 · see citing works
Modulation of hippocampal calcium signalling and plasticity by serine/threonine protein phosphatases
Koss, D. J., Hindley, K. P., Riedel, G., & Platt, B. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04579.x · Cited by 28 · see citing works
Martínez‐Cué, C., & Rueda, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186906 · Cited by 26 · see citing works
Zhang, Y., Li, H.-L., Wang, D.-L., Liu, S.-J., & Wang, J. (2006) · Journal of Neural Transmission · doi:10.1007/s00702-005-0421-2 · Cited by 27 · see citing works
Self-citationCho, K., Yoon, S. Y., Choi, J. E., Kang, H. J., Jang, H. Y., & Kim, D. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.05.056 · Cited by 27 · see citing works
Saul, N., Chakrabarti, S., Stürzenbaum, S. R., Menzel, R., & Steinberg, C. E. W. (2014) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2014.09.007 · Cited by 26 · see citing works
Activation of eukaryotic initiation factor-2α-kinases in okadaic acid-treated neurons
Kim, S. M., Yoon, S., Choi, J. E., Park, J. S., Choi, J. M., Nguyen, T. T., & Kim, D. H. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.06.016 · Cited by 26 · see citing works
Mallozzi, C., Franceschi, L. D., Brugnara, C., & Stasi, A. M. M. D. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.02.021 · Cited by 24 · see citing works
Stein, T. D., & Johnson, J. A. (2003) · Reviews in the Neurosciences · doi:10.1515/revneuro.2003.14.4.317 · Cited by 24 · see citing works
- 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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