Ciliary neurotrophic factor (CNTF) enhances myelin formation: a novel role for CNTF and CNTF-related molecules.
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.
Stankoff
Bruno
B
Biologie des Interactions Neurones-Glie, Institut National de la Santé et de la Recherche Médicale Unité 495, Paris cedex 13, France.
Aigrot
Marie-Stéphane
MS
Noël
Frédéric
F
Wattilliaux
Aurélie
A
Zalc
Bernard
B
Lubetzki
Catherine
C
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism; D001923:Brain Chemistry; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D018920:Coculture Techniques; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D006133:Growth Substances; C494200:Il6st protein, mouse; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D011993:Recombinant Fusion Proteins; D050822:Cytokine Receptor gp130; D001616:beta-Galactosidase