Progressive neurodegeneration in C-elegans model of tauopathy
Progressive neurodegeneration in C-elegans model of tauopathy
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DOI：
10.1016/j.nbd.2005.03.017
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发表时间：
2005-11-01
影响因子：
6.1
通讯作者：
Ihara, Y
中科院分区：
文献类型：
--
作者：
Miyasaka, T;Ding, Z;Ihara, Y
在与17号染色体（FTDP-17）相关的额颞叶痴呆和帕金森综合征家族中发现tau基因的各种突变，表明野生型或突变型tau的毒性功能获得是广泛神经元损失的机制。因此，我们产生了转基因线虫（秀丽隐杆线虫）表达野生型或突变体（P301 L和R406 W）tau的触摸（机械感觉）神经元。表达野生型tau的蠕虫在整个生命周期内触摸反应略有下降，而表达突变型tau的蠕虫则表现出大幅且渐进的下降。当触觉神经元丧失功能时，神经炎性异常突出，后期微管丢失明显。相当一部分退化的神经元在细胞体和神经元突起中形成tau积聚。这种神经元功能障碍与凋亡过程无关，因为在ced-3或ced-4缺陷背景下观察到触摸异常几乎没有恢复。GSK 3的表达导致触摸反应轻微恶化，而HSP 70的表达导致一些改善。(c)2005年爱思唯尔公司All rights reserved.
Discovery of various mutations in the tau gene among frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) families suggests gain-of-toxic function of wild-type or mutant tau as the mechanism for extensive neuronal loss. We thus generated transgenic nematode (Caenorhabditis elegans) expressing wild-type or mutant (P301L and R406W) tau in the touch (mechanosensory) neurons. Whereas the worm expressing wild-type tau showed a small decrease in the touch response across the lifespan, the worm expressing mutant tau displayed a large and progressive decrease. When the touch neurons lost their function, neuritic abnormalities were found prominent, and microtubular loss became remarkable in the later stage. A substantial fraction of degenerating neurons developed tau accumulation in the cell body and neuronal processes. This neuronal dysfunction is not related to the apoptotic process because little recovery from touch abnormality was observed in the ced-3 or ced-4-deficient background. Expression of GSK3 brought about slight deterioration in the touch response, while expression of HSP70 led to some improvement. (c) 2005 Elsevier Inc. All rights reserved.