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Glycogen synthase kinase-3β phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice

(2000) JOURNAL OF BIOLOGICAL CHEMISTRY. 275(52). p.41340-41349
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Abstract
Protein tau filaments in brain of patients suffering from Alzheimer's disease, frontotemporal dementia, and other tauopathies consist of protein tau that is hyperphosphorylated.,The responsible kinases operating in vivo in neurons still need to be identified. Here we demonstrate that glycogen synthase kinase-3 beta (GSK-3 beta) is an effective kinase for protein tau in cerebral neurons in vivo in adult GSK-3 beta and GSK-3 beta x human tau40 transgenic mice; Phosphorylated protein tau migrates slower during electrophoretic separation and is revealed by phosphorylation-dependent anti-tau antibodies in Western blot analysis. In addition, its capacity to bind to re-assembled paclitaxel (Taxol(R))-stabilized microtubules is reduced, compared with protein tau isolated from mice not overexpressing GSK-3 beta. Co-expression of GSK-3 beta reduces the number of axonal dilations and alleviates the motoric impairment that was typical for single htau40 transgenic animals (Spittaels, K., Van den Haute, C., Van Dorpe, J., Bruynseels, K., Vandezande, K., Laenen, I., Geerts, H., Mercken, M., Sciot, R., Van Lommel, A., Loos, R., and Van Leuven, F. (1999) Am. J. Pathol. 155, 2153-2165). Although more hyperphosphorylated protein tau is available, neither an increase in insoluble protein tau aggregates nor the presence of paired helical filaments or tangles was observed. These findings could have therapeutic implications in the field of neurodegeneration, as discussed.
Keywords
AMYLOID PRECURSOR PROTEIN, PAIRED HELICAL FILAMENTS, DISEASE-LIKE PHOSPHORYLATION, ALZHEIMER-LIKE STATE, HUMAN BRAIN TAU, INTACT-CELLS, KINASE-I, MICROTUBULE-BINDING, NEUROFIBRILLARY TANGLES, MONOCLONAL-ANTIBODIES

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Citation

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Chicago
Spittaels, Kurt, Chris Van den Haute, Jo Van Dorpe, Hugo Geerts, Marc Mercken, Koen Bruynseels, Reena Lasrado, et al. 2000. “Glycogen Synthase Kinase-3β Phosphorylates Protein Tau and Rescues the Axonopathy in the Central Nervous System of Human Four-repeat Tau Transgenic Mice.” Journal of Biological Chemistry 275 (52): 41340–41349.
APA
Spittaels, Kurt, Van den Haute, C., Van Dorpe, J., Geerts, H., Mercken, M., Bruynseels, K., Lasrado, R., et al. (2000). Glycogen synthase kinase-3β phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice. JOURNAL OF BIOLOGICAL CHEMISTRY, 275(52), 41340–41349.
Vancouver
1.
Spittaels K, Van den Haute C, Van Dorpe J, Geerts H, Mercken M, Bruynseels K, et al. Glycogen synthase kinase-3β phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice. JOURNAL OF BIOLOGICAL CHEMISTRY. 2000;275(52):41340–9.
MLA
Spittaels, Kurt, Chris Van den Haute, Jo Van Dorpe, et al. “Glycogen Synthase Kinase-3β Phosphorylates Protein Tau and Rescues the Axonopathy in the Central Nervous System of Human Four-repeat Tau Transgenic Mice.” JOURNAL OF BIOLOGICAL CHEMISTRY 275.52 (2000): 41340–41349. Print.
@article{5940728,
  abstract     = {Protein tau filaments in brain of patients suffering from Alzheimer's disease, frontotemporal dementia, and other tauopathies consist of protein tau that is hyperphosphorylated.,The responsible kinases operating in vivo in neurons still need to be identified. Here we demonstrate that glycogen synthase kinase-3 beta (GSK-3 beta) is an effective kinase for protein tau in cerebral neurons in vivo in adult GSK-3 beta and GSK-3 beta x human tau40 transgenic mice; Phosphorylated protein tau migrates slower during electrophoretic separation and is revealed by phosphorylation-dependent anti-tau antibodies in Western blot analysis. In addition, its capacity to bind to re-assembled paclitaxel (Taxol(R))-stabilized microtubules is reduced, compared with protein tau isolated from mice not overexpressing GSK-3 beta. Co-expression of GSK-3 beta reduces the number of axonal dilations and alleviates the motoric impairment that was typical for single htau40 transgenic animals (Spittaels, K., Van den Haute, C., Van Dorpe, J., Bruynseels, K., Vandezande, K., Laenen, I., Geerts, H., Mercken, M., Sciot, R., Van Lommel, A., Loos, R., and Van Leuven, F. (1999) Am. J. Pathol. 155, 2153-2165). Although more hyperphosphorylated protein tau is available, neither an increase in insoluble protein tau aggregates nor the presence of paired helical filaments or tangles was observed. These findings could have therapeutic implications in the field of neurodegeneration, as discussed.},
  author       = {Spittaels, Kurt and Van den Haute, Chris and Van Dorpe, Jo and Geerts, Hugo and Mercken, Marc and Bruynseels, Koen and Lasrado, Reena and Vandezande, Kris and Laenen, Isabelle and Boon, Tim and Van Lint, Jo and Vandenheede, Jacky and Moechars, Dieter and Loos, Ruth and Van Leuven, Fred},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  keyword      = {AMYLOID PRECURSOR PROTEIN,PAIRED HELICAL FILAMENTS,DISEASE-LIKE PHOSPHORYLATION,ALZHEIMER-LIKE STATE,HUMAN BRAIN TAU,INTACT-CELLS,KINASE-I,MICROTUBULE-BINDING,NEUROFIBRILLARY TANGLES,MONOCLONAL-ANTIBODIES},
  language     = {eng},
  number       = {52},
  pages        = {41340--41349},
  title        = {Glycogen synthase kinase-3\ensuremath{\beta} phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice},
  url          = {http://dx.doi.org/10.1074/jbc.M006219200},
  volume       = {275},
  year         = {2000},
}

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