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

Alejandra Catenaccio; Maica Llavero Hurtado; Paula Diaz; Douglas J. Lamont; Thomas M. Wishart; Felipe A. Court

doi:10.1038/cddis.2017.489

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

Alejandra Catenaccio
, Maica Llavero Hurtado
, Paula Diaz
, Douglas J. Lamont
, Thomas M. Wishart
, Felipe A. Court (Lead / Corresponding author)

Centre for Advanced Scientific Technologies

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

246 Downloads (Pure)

Abstract

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.

Original language	English
Article number	e3166
Pages (from-to)	1-14
Number of pages	14
Journal	Cell Death and Disease
Volume	8
Issue number	11
DOIs	https://doi.org/10.1038/cddis.2017.489
Publication status	Published - 9 Nov 2017

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Journal article

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10.1038/cddis.2017.489Licence: CC BY

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title = "Molecular analysis of axonal-intrinsic and glial-associated co-regulation of axon degeneration",

abstract = "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.",

keywords = "Journal article",

author = "Alejandra Catenaccio and \{Llavero Hurtado\}, Maica and Paula Diaz and Lamont, \{Douglas J.\} and Wishart, \{Thomas M.\} and Court, \{Felipe A.\}",

note = "This work was supported by grants from Geroscience Center for Brain Health and Metabolism (FONDAP-15150012), Fondo Nacional de Desarrollo Cient{\'i}fico y Tecnol{\'o}gico (FONDECYT, No. 1070377), Millennium Nucleus RC120003 and Ring Initiative ACT1109. MLH is supported by a Darwin Trust Studentship and TMW is funded by the BBSRC (Roslin Institute strategic program grant – BB/J004332/1) and the MRC (MR/M010341/1).",

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doi = "10.1038/cddis.2017.489",

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AU - Catenaccio, Alejandra

AU - Llavero Hurtado, Maica

AU - Diaz, Paula

AU - Lamont, Douglas J.

AU - Wishart, Thomas M.

AU - Court, Felipe A.

N1 - This work was supported by grants from Geroscience Center for Brain Health and Metabolism (FONDAP-15150012), Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT, No. 1070377), Millennium Nucleus RC120003 and Ring Initiative ACT1109. MLH is supported by a Darwin Trust Studentship and TMW is funded by the BBSRC (Roslin Institute strategic program grant – BB/J004332/1) and the MRC (MR/M010341/1).

PY - 2017/11/9

Y1 - 2017/11/9

N2 - 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.

AB - 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.

KW - Journal article

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DO - 10.1038/cddis.2017.489

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JO - Cell Death and Disease

JF - Cell Death and Disease

IS - 11

M1 - e3166

ER -

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

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