Huntington's disease is a four-repeat tauopathy with tau nuclear rods
Huntington's disease is a four-repeat tauopathy with tau nuclear rods
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DOI：
10.1038/nm.3617
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发表时间：
2014-08-01
期刊：
影响因子：
82.9
通讯作者：
Lucas, Jose J.
中科院分区：
文献类型：
--
作者：
Fernandez-Nogales, Marta;Cabrera, Jorge R.;Lucas, Jose J.
在MAPT基因内含子突变的家庭中，含有3或4个微管结合重复序列的tau亚型不平衡导致17号染色体相关的帕金森病额颞叶痴呆（FTDP-17）。在这里，我们报告了亨廷顿病（HD）患者大脑中mRNA和蛋白质水平的同等失衡，以及总tau水平的增加，以及沿神经元核的杆状tau沉积。这些tau核棒显示出有序的丝状超微结构，可以在先前报道的HD大脑中发现填充神经元核凹痕。最后，富含丝氨酸/精氨酸的剪接因子-6的改变与tau错误剪接一致，tau基因敲除背景下突变体HTT转基因小鼠运动异常的减弱证明了tau在HD发病中的作用。
An imbalance of tau isoforms containing either three or four microtubule-binding repeats causes frontotemporal dementia with parkinsonism linked to-chromosome 17 (FTDP-17) in families with intronic mutations in the MAPT gene. Here we report equivalent imbalances at the mRNA and protein levels and increased total tau levels in the brains of subjects with Huntington's disease (HD) together with rod-like tau deposits along neuronal nuclei. These tau nuclear rods show an ordered filamentous ultrastructure and can be found filling the neuronal nuclear indentations previously reported in HD brains. Finally, alterations in serine/arginine-rich splicing factor-6 coincide with tau missplicing, and a role of tau in HD pathogenesis is evidenced by the attenuation of motor abnormalities of mutant HTT transgenic mice in tau knockout backgrounds.