Global axonal transport rates are unaltered in htau mice in vivo.
Global axonal transport rates are unaltered in htau mice in vivo.
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DOI：
10.3233/jad-130671
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Nixon RA
中科院分区：
文献类型：
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作者：
Yuan A;Kumar A;Sasaki T;Duff K;Nixon RA
基于微管的轴突运输被认为在阿尔茨海默病中被全面破坏，部分原因是tau表达或磷酸化的改变。我们之前的研究表明，沿视网膜神经节轴突的轴突运输速率不受正常小鼠tau蛋白缺失或野生型人类tau蛋白过表达的影响。在这里，我们报告了在缺乏小鼠tau蛋白的情况下，htau小鼠表达的人类tau蛋白水平高出3倍，尽管在一些神经元中存在异常过度磷酸化的tau蛋白，但htau小鼠也表现出正常的快慢运输动力学。此外，慢转运标志物（神经丝光亚基）和快转运标志物（snap25）沿视轴突呈正态分布。这些研究表明，即使与有限程度的tau病理相关，人类tau过表达也不一定会损害体内的一般轴突运输功能。本研究发表在《阿尔茨海默病杂志》上，以纪念英格·格伦克·伊克巴尔，并庆祝她对阿尔茨海默病研究的贡献。
Microtubule-based axonal transport is believed to become globally disrupted in Alzheimer’s disease in part due to alterations of tau expression or phosphorylation. We previously showed that axonal transport rates along retinal ganglion axons are unaffected by deletion of normal mouse tau or by overexpression of wild-type human tau. Here, we report that htau mice expressing 3-fold higher levels of human tau in the absence of mouse tau also display normal fast and slow transport kinetics despite the presence of abnormally hyperphosphorylated tau in some neurons. In addition, markers of slow transport (neurofilament light subunit) and fast transport (snap25) exhibit normal distributions along optic axons of these mice. These studies demonstrate that human tau overexpression, even when associated with a limited degree of tau pathology, does not necessarily impair general axonal transport function in vivo. This investigation is contributed for the issue of Journal of Alzheimer’s Disease dedicated to the memory of Inge Grunke-Iqbal and to the celebration of her contributions to Alzheimer’s disease research.