The C-Terminus of Tau Protein Plays an Important Role in Its Stability and Toxicity
The C-Terminus of Tau Protein Plays an Important Role in Its Stability and Toxicity
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DOI：
10.1007/s12031-014-0314-7
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发表时间：
2015-01-01
影响因子：
3.1
通讯作者：
Dou, Fei
中科院分区：
文献类型：
--
作者：
Geng, Junhua;Xia, Lu;Dou, Fei
在阿尔茨海默病患者的神经元和神经原纤维缠结中发现蛋白水解产生的tau片段，促进了对截断tau毒性的研究。然而，蛋白水解诱导的tau毒性的详细机制尚不清楚，在某些情况下甚至存在争议。在本研究中，我们以果蝇为模型，在体内评估了一组截短的tau片段的毒性，发现由于c端截短的tau片段的不稳定特性，携带c端截短的tau的果蝇表现出较小的毒性。在培养的果蝇Kc细胞中进行的进一步研究表明，c端截短的tau片段比全长tau或n端截短的片段降解更快。总的来说，我们的数据暗示tau蛋白水解是体内介导tau降解和神经毒性的重要途径。
The identification of tau fragments generated by proteolysis in the neurons of AD patients and in neurofibrillary tangles encourages research on the toxicity of truncated tau. However, the detailed mechanism underlying the proteolysis-induced toxicity of tau is not clear and even controversial in some cases. In the present study, we used Drosophila as a model to evaluate the toxicity of a set of truncated tau fragments in vivo and found that the flies harboring C-terminal-truncated tau exhibited less toxicity due to the unstable characteristic of C-terminal-truncated tau fragments. Further study carried out in cultured Drosophila Kc cells revealed that C-terminal-truncated tau fragments degrade faster than full-length tau or N-terminal-truncated fragments. Collectively, our data implicate proteolysis of tau as an important pathway mediating tau degradation and neurotoxicity in vivo.