Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms
Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms
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DOI：
10.1523/jneurosci.4637-04.2005
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发表时间：
2005-06-01
影响因子：
5.3
通讯作者：
Davies, P
中科院分区：
文献类型：
--
作者：
Andorfer, C;Acker, CM;Davies, P
微管相关蛋白tau基因的突变与几种称为tau蛋白病的神经退行性疾病中的神经元缠结（NFT）形成有关;然而，阿尔茨海默病中没有tau突变，尽管这种疾病也以NFT形成和细胞死亡为特征。重要的是，tau蛋白介导的神经元死亡的机制仍然难以捉摸。在不存在小鼠tau的情况下表达非突变型人tau的老年小鼠（htau小鼠）发生NFT和广泛的细胞死亡。在htau小鼠中研究了神经元死亡的机制，令人惊讶的是，tau细丝的存在与单个细胞内的死亡没有直接相关性，这表明细胞死亡可以独立于NFT形成而发生。我们的观察结果表明，神经退行性变的机制涉及细胞周期蛋白和DNA合成的重新表达，表明非突变的tau蛋白病理学和神经退行性变可能通过异常，不完整的细胞周期折返。
Mutations in the microtubule-associated protein tau gene have been linked to neurofibrillary tangle (NFT) formation in several neuro-degenerative diseases known as tauopathies; however, no tau mutations occur in Alzheimer's disease, although this disease is also characterized by NFT formation and cell death. Importantly, the mechanism of tau-mediated neuronal death remains elusive. Aged mice expressing nonmutant human tau in the absence of mouse tau (htau mice) developed NFTs and extensive cell death. The mechanism of neuron death was investigated in htau mice, and surprisingly, the presence of tau filaments did not correlate directly with death within individual cells, suggesting that cell death can occur independently of NFT formation. Our observations show that the mechanism of neurodegeneration involved reexpression of cell-cycle proteins and DNA synthesis, indicating that nonmutant tau pathology and neurodegeneration may be linked via abnormal, incomplete cell-cycle reentry.