Molecular analysis of axonal-intrinsic and glial-associated co-regulation of axon degeneration.

Molecular analysis of axonal-intrinsic and glial-associated co-regulation of axon degeneration.
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轴突内部和胶质相关的轴突变性共同调节的分子分析。

DOI:
10.1038/cddis.2017.489
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发表时间:
2017-11-09
影响因子:
9
通讯作者:
Court FA
Court FA
中科院分区:
生物学1区
文献类型:
--
作者:
Catenaccio A;Llavero Hurtado M;Diaz P;Lamont DJ;Wishart TM;Court FA

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Wallerian变性是一种与轴突变性密切相关的主动程序,是神经损伤后轴突再生和功能恢复所必需的。在这里,我们提供了一个功能性的分子基础,我们的理解复杂的非细胞自主神经胶质细胞的轴突变性的调节作用。为了阐明轴突变性的分子机制的复杂性,我们采用了多模型,无偏的,在体内的方法相结合的形态学评估和定量蛋白质组学与基于计算机的高阶功能聚类的内在和外在的过程中遗传解耦华勒变性。强调了神经胶质细胞在早期阶段通过类轴突分裂过程和与线粒体功能障碍相关的轴突解体的细胞自主阶段使轴突碎片化的关键作用。
Wallerian degeneration is an active program tightly associated with axonal degeneration, required for axonal regeneration and functional recovery after nerve damage. Here we provide a functional molecular foundation for our undertstanding of the complex non-cell autonomous role of glial cells in the regulation of axonal degeneration. To shed light on the complexity of the molecular machinery governing axonal degeneration we employ a multi-model, unbiased, in vivo approach combining morphological assesment and quantitative proteomics with in silico-based higher order functional clustering to genetically uncouple the intrinsic and extrinsic processes governing Wallerian degeneration. Highlighting a pivotal role for glial cells in the early stages fragmenting the axon by a cytokinesis-like process and a cell autonomous stage of axonal disintegration associated to mitochondrial dysfunction.
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发表时间: 2011-11-15
影响因子: 3.5
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