CNTF is a polypeptide trophic factor, member of the alpha-helical cytokine superfamily. It was initially purified from the chick eye on the basis of its ability to promote survival of E8 chick ciliary ganglion neurons in culture. CNTF is synthesized by glia both in the CNS and PNS3 and it has been demonstrated that CNTF is ubiquitously distributed in neurons and glia throughout the rodent brain. CNTF effects are mediated by a tripartite receptor complex consisting of two signal-transducing subunits (leukemia inhibitory factor receptor, gp130) and a CNTF-specific ligand-binding-subunit (CNTFRα).n CNTFRα is anchored to the membrane by a glycosyl-phosphatidylinositol (GPI) linkage and lacks the intracellular signaling moiety. It can be cleaved from the GPI anchor to yield a soluble form of the receptor (sCNTFRα).nCNTF binds to CNTFRα, the latter associates with gp130 which recruits LIFR. This leads to the activation of a signaling cascade involving the JAK/STAT pathway.nCNTFRα knockout mice die within 24 hours after birth as opposed to CNTF knock animals which are viable. This strongly suggest that CNTFRα has other ligands besides CNTF. Indeed, CLC/CLF complex (cardiotrophin like cytokine/cytokine-like factor-1) binds CNTFRα and activates a similar signaling pathway to that of CNTF.
