...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular biology of the cell >Mitotic defects lead to neuronal aneuploidy and apoptosis in frontotemporal lobar degeneration caused by MAPT mutations
【24h】

Mitotic defects lead to neuronal aneuploidy and apoptosis in frontotemporal lobar degeneration caused by MAPT mutations

机译：有丝分裂缺陷导致由MAPT突变引起的额发射叶片变性的神经元非倍性和细胞凋亡

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Mutant Tau (MAPT) can lead to frontotemporal lobar degeneration (FTLD). Previous studies associated MAPT mutations and altered function with aneuploidy and chromosome instability in human lymphocytes and in Drosophila development. Here we examine whether FTLD-causing mutations in human MAPT induce aneuploidy and apoptosis in the mammalian brain. First, aneuploidy was found in brain cells from MAPT mutant transgenic mice expressing FTLD mutant human MAPT. Then brain neurons from mice homozygous or heterozygous for the Tau (Mapt) null allele were found to exhibit increasing levels of aneuploidy with decreasing Tau gene dosage. To determine whether aneuploidy leads to neurodegeneration in FTLD, we measured aneuploidy and apoptosis in brain cells from patients with MAPT mutations and identified both increased aneuploidy and apoptosis in the same brain neurons and glia. To determine whether there is a direct relationship between MAPT-induced aneuploidy and apoptosis, we expressed FTLD-causing mutant forms of MAPT in karyotypically normal human cells and found that they cause aneuploidy and mitotic spindle defects that then result in apoptosis. Collectively, our findings reveal a neurodegenerative pathway in FTLD-MAPT in which neurons and glia exhibit mitotic spindle abnormalities, chromosome mis-segregation, and aneuploidy, which then lead to apoptosis.
机译：突变体Tau（Mapt）可以导致额定颞叶片退化（FTLD）。以前的研究相关的Mapt突变和在人淋巴细胞和果蝇发育中的交氮细胞和染色体不稳定性改变功能。在这里，我们检查人类mapt中的FTLD导致突变是否在哺乳动物脑中诱导非洲倍性和细胞凋亡。首先，在表达FTLD突变体MAPT的MAPT突变转基因小鼠中，在脑细胞中发现短倍性。然后发现来自纯合或杂合的小鼠的脑神经元（MAPT）无效等位基因，表现出随着TAU基因剂量降低的增加的非整倍性水平。为了确定非倍性是否导致FTLD中的神经变性，我们从MAPT突变患者中测量了脑细胞中的一种非血浆和凋亡，并确定了同一脑神经元和胶质胶中的增加的非整倍性和细胞凋亡。为了确定MAPT诱导的非洲倍性和凋亡之间是否存在直接关系，我们表达了核型正常人体细胞中MAPT的FTLD突变形式，发现它们导致动脉倍性和有丝分裂的主轴缺陷，然后导致细胞凋亡。统称，我们的研究结果揭示了FTLD-MAPT中的神经变性途径，其中神经元和胶质胶质表现出有丝分子主轴异常，染色体的误解和非整倍性，然后导致细胞凋亡。

著录项

相似文献

  • 外文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号