Ectopic localization of phosphorylated histone H3 in Alzheimer's disease: a mitotic catastrophe?
Ectopic localization of phosphorylated histone H3 in Alzheimer's disease: a mitotic catastrophe?
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DOI：
10.1007/s00401-003-0684-3
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发表时间：
2003-05-01
影响因子：
12.7
通讯作者：
Smith, MA
中科院分区：
文献类型：
--
作者：
Ogawa, O;Zhu, XW;Smith, MA
尽管他们的终末分化状态，脆弱的神经元在阿尔茨海默病（AD）显示细胞周期激活的证据，表明有丝分裂功能障碍可能是重要的疾病的发病机制。为了进一步阐明有丝分裂过程在疾病发病机制中的作用，我们研究了磷酸化组蛋白H3，这是细胞分裂过程中染色体致密化的关键组分。与有丝分裂机制的激活一致，我们发现AD中海马神经元中磷酸化的历史H3增加。然而，而不是在细胞核内的活跃分裂的细胞，激活磷酸化组蛋白H3在AD中被限制到神经元细胞质，尽管有丝分裂机制的激活。因此，磷酸化组蛋白H3的异常细胞质定位表明有丝分裂灾难导致AD中神经元功能障碍和神经退行性变。
Despite their terminally differentiated status, vulnerable neurons in Alzheimer's disease (AD) display evidence of cell cycle activation, suggesting that mitotic dysfunction may be important in disease pathogenesis. To further delineate the role of mitotic processes in disease pathogenesis, we investigated phosphorylated histone H3, a key component involved in chromosome compaction during cell division. Consistent with an activation of the mitotic machinery, we found an increase in phosphorylated historic H3 in hippocampal neurons in AD. However, rather than within the nucleus as in actively dividing cells, activated phosphorylated histone H3 in AD is restricted to the neuronal cytoplasm despite activation of the mitotic machinery. Therefore, the aberrant cytoplasmic localization of phosphorylated histone H3 indicates a mitotic catastrophe that leads to neuronal dysfunction and neurodegeneration in AD.