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Canadian Association of Neurosciences Review: Regulation of Myelination by Trophic Factors and Neuron-Glial Signaling

Published online by Cambridge University Press:  02 December 2014

Giorgia Melli
Affiliation:
The Neuromuscular Diseases Unit, IRCSS Foundation Neurological Institute Carlo Besta, via Celoria, 11 20133 - Milan, Italy
Ahmet Höke
Affiliation:
Department of Neurology and Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD, USA
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Abstract

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Myelination in the nervous system is a tightly regulated process that is mediated by both soluble and non-soluble factors acting on axons and glial cells. This process is bi-directional and involves a variety of neurotrophic and gliotrophic factors acting in paracrine and autocrine manners. Neuron-derived trophic factors play an important role in the control of early proliferation and differentiation of myelinating glial cells. At later stages of development, same molecules may play a different role and act as inducers of myelination rather than cell survival signals for myelinating glial cells. In return, myelinating glial cells provide trophic support for axons and protect them from injury. Chronic demyelination leads to secondary axonal degeneration that is responsible for long-term disability in primary demyelinating diseases such as multiple sclerosis and inherited demyelinating peripheral neuropathies. A better understanding of the molecular mechanisms controlling myelination may yield novel therapeutic targets for demyelinating nervous system disorders.

Résumé:

RÉSUMÉ:

Régulation de la myélinisation par des facteurs trophiques et par la signalisation de la névroglie. La myélinisation du système nerveux est un processus étroitement régulé, qui est médié par des facteurs solubles et non solubles agissant sur les axones et les cellules gliales. Ce processus est bidirectionnel et implique des facteurs neurotrophes et gliotrophes variés agissant de façon paracrine et autocrine. Des facteurs trophiques dérivés des neurones jouent un rôle important dans le contrôle de la prolifération et de la différenciation précoce des cellules gliales myélinisantes. Àdes étapes ultérieures du développement, les mêmes acteurs peuvent jouer un rôle différent et agir comme inducteurs de la myélinisation plutôt que dans la signalisation de la survie cellulaire des cellules gliales myélinisantes. En retour, les cellules gliales myélinisantes fournissent un support trophique aux axones et les protègent de lésions. Une démyélinisation chronique entraî une dégénérescence axonale secondaire qui est responsable de l'invalidité à long terme observée dans les maladies démyélinisantes primaires comme la sclérose en plaques et les neuropathies périphériques démyélinisantes héréditaires. Une meilleure compréhension des mécanismes moléculaires contrôlant la myélinisation pourrait identifier des cibles thérapeutiques nouvelles pour le traitement des maladies démyélinisantes du système nerveux.

Type
Original Articles
Copyright
Copyright © The Canadian Journal of Neurological 2007

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