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

作者:Catenaccio Alejandra; Hurtado Maica Llavero; Diaz Paula; Lamont Douglas J; Wishart Thomas M; Court Felipe A*
来源:Cell Death & Disease, 2017, 8(11): e3166.
DOI:10.1038/cddis.2017.489

摘要

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.

  • 出版日期2017-11