Ciliary Neurotrophic Factor (CNTF) Enhances Myelin Formation: a Novel Role for CNTF and CNTF-related Molecules

Overview

Journal J Neurosci

Specialty Neurology

Date 2002 Nov 6

PMID 12417647

Citations 106

Authors

Bruno Stankoff

Marie-Stephane Aigrot

Frederic Noel

Aurelie Wattilliaux

Bernard Zalc

Catherine Lubetzki

Affiliations

Soon will be listed here.

Abstract

In multiple sclerosis, myelin repair is generally insufficient despite the relative survival of oligodendrocytes within the plaques and the recruitment of oligodendrocyte precursors. Promoting remyelination appears to be a crucial therapeutic challenge. Using a newly developed enzymatic index of myelination, we screened different neurotrophic factors for their ability to enhance myelination. Neurotrophins [NGF, neurotrophin-3 (NT-3), NT-4/5, BDNF], glial cell line-derived neurotrophic factor (GDNF)-related factors (GDNF, neurturin), and growth factors such as PDGF-AA, FGF-2, and insulin did not increase myelinogenesis. In contrast, among factors belonging to the CNTF family, CNTF, leukemia inhibitory factor, cardiotrophin-1, and oncostatin M induced a strong promyelinating effect. We provide evidence that CNTF acts on oligodendrocytes by favoring their final maturation, and that this effect is mediated through the 130 kDa glycoprotein receptor common to the CNTF family and transduced through the Janus kinase pathway. Our results demonstrate a novel role for neurotrophic factors of the CNTF family and raise the possibility that these factors might be of therapeutic interest to promote remyelination in multiple sclerosis.

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