Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago 8580745, Chile.
FONDAP Center for Geroscience, Brain Health and Metabolism, Santiago, Chile.
Cell Death Dis. 2017 Nov 9;8(11):e3166. doi: 10.1038/cddis.2017.489.
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.
华勒氏变性是一个与轴突变性紧密相关的主动过程，对于神经损伤后的轴突再生和功能恢复是必需的。在这里，我们为理解神经胶质细胞在调控轴突变性中的复杂非细胞自主作用提供了一个功能分子基础。为了阐明调控轴突变性的分子机制的复杂性，我们采用了一种多模型、无偏倚的体内方法，结合形态评估和定量蛋白质组学以及基于计算的高阶功能聚类，从遗传上分离出调控华勒氏变性的内在和外在过程。研究结果突出了神经胶质细胞在早期阶段的关键作用，通过类似于细胞分裂的过程使轴突碎片化，并与线粒体功能障碍相关的轴突解体的自主阶段。
