کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
330319 | 1433638 | 2009 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Wnt-pathway activation during the early stage of neurodegeneration in FTDP-17 mice Wnt-pathway activation during the early stage of neurodegeneration in FTDP-17 mice](/preview/png/330319.png)
Glycogen synthase kinase-3beta (GSK-3β), a key component of the Wnt signaling pathway, has been recognized as an important tau kinase with a potential pathogenic role in dementia. We have previously shown that GSK-3β-induced tau-hyperphosphorylation and Wnt-activation enhance tau-induced degeneration in Drosophila. Here, we demonstrate that Wnt-activation occurs prior to 3 months of age in the JNPL3 mouse model of frontotemporal dementia (FTD). We observed that GSK-3β becomes associated with insoluble tau, concomitant with the increase in the downstream Wnt-pathway component β-catenin. We demonstrate that this induces downstream Wnt signaling via the activation of nuclear transcription factors associated with β-catenin, suggesting that Wnt-pathway activation is an early feature of the neurodegenerative process.
Journal: Neurobiology of Aging - Volume 30, Issue 1, January 2009, Pages 14–21