کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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329543 | 1433667 | 2006 | 11 صفحه PDF | دانلود رایگان |

Here we have tested whether tau modification either by point mutation or by hyperphosphorylation can exert maximal pathogenic effects or if, on the contrary, both types of tau modifications can act synergistically to induce neuropathology. For this, we have combined transgenic mice overexpressing the enzyme GSK-3β (Tet/GSK-3β mice), with transgenic mice expressing Tau with a triple FTDP-17 mutation which develop prefibrillar tau-aggregates (VLW mice). Tet/GSK-3β/VLW transgenic mice show tau hyperphosphorylation in hippocampal neurons. This is accompanied by thioflavin-S staining, and formation of filaments similar in width to those found in tauophaties. Finally, the atrophy of the hippocampal dentate gyrus observed in Tet/GSK-3β mice develops much faster in Tet/GSK-3β/VLW mice. All these morphological and biochemical data demonstrate that there is a synergistic contribution of both types of tau modifications and that the potential of GSK-3 inhibitors for AD therapeutics also extends to tauopathies caused by point mutations in tau gene.
Journal: Neurobiology of Aging - Volume 27, Issue 9, September 2006, Pages 1258–1268