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.
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FTDP-17 小鼠神经变性早期阶段的 Wnt 通路激活。
DOI：
10.1016/j.neurobiolaging.2007.05.015
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发表时间：
2009
影响因子：
4.2
通讯作者：
Geschwind,DanielH
中科院分区：
文献类型：
--
作者：
Wiedau-Pazos,Martina;Wong,Eugene;Solomon,Esther;Alarcon,Maricela;Geschwind,DanielH
糖原合成酶激酶-3β (GSK-3β)是Wnt信号通路的关键组成部分，已被认为是一种重要的tau激酶，在痴呆中具有潜在的致病作用。我们之前已经证明gsk -3β诱导的tau过度磷酸化和wnt激活增强了果蝇tau诱导的变性。在这里，我们证明在JNPL3额颞叶痴呆（FTD）小鼠模型中，wnt激活发生在3个月大之前。我们观察到GSK-3β与不溶性tau蛋白相关，并伴随着下游wnt通路成分β-连环蛋白的增加。我们证明，这通过激活与β-catenin相关的核转录因子诱导下游Wnt信号传导，表明Wnt通路激活是神经退行性过程的早期特征。
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.