Johansson Sara, Jämsä Anne, Vasänge Mervi, Winblad Bengt, Luthman Johan, Cowburn Richard F
Local Discovery Research Area CNS & Pain Control, AstraZeneca, Södertälje, Sweden.
Neuroreport. 2006 Jun 26;17(9):907-11. doi: 10.1097/01.wnr.0000221844.35502.29.
The hallmarks of Alzheimer's disease include extracellular plaques primarily consisting of amyloid-beta peptide and intracellular neurofibrillary tangles composed of highly phosphorylated tau protein. We report that exposure of organotypic hippocampal cultures to synthetic amyloid-beta peptide(25-35) (50 microM, 96 h) causes neurodegeneration concomitant with a significant increase in tau phosphorylation at the Ser epitope (+60%). Furthermore, the level of active glycogen synthase kinase-3beta (GSK-3beta [pTyr]) was increased (+55%) after amyloid-beta peptide(25-35) exposure. These findings support the role of amyloid-beta peptide as a mediator of tau phosphorylation and demonstrate the usefulness of organotypic cultures for investigating the link between amyloid-beta peptide-induced neurotoxicity and tau phosphorylation. Our results also confirm that amyloid-beta peptide induces activation of glycogen synthase kinase-3beta.
阿尔茨海默病的标志包括主要由β-淀粉样肽组成的细胞外斑块和由高度磷酸化的tau蛋白构成的细胞内神经原纤维缠结。我们报告，将器官型海马培养物暴露于合成的β-淀粉样肽（25-35）（50微摩尔，96小时）会导致神经退行性变，同时丝氨酸表位处的tau磷酸化显著增加（+60%）。此外，暴露于β-淀粉样肽（25-35）后，活性糖原合酶激酶-3β（GSK-3β [pTyr]）水平升高（+55%）。这些发现支持β-淀粉样肽作为tau磷酸化介质的作用，并证明了器官型培养物在研究β-淀粉样肽诱导的神经毒性与tau磷酸化之间联系方面的有用性。我们的结果还证实，β-淀粉样肽可诱导糖原合酶激酶-3β的激活。
