CNTF is a polypeptide trophic factor, member of the alpha-helical cytokine superfamily¹. It was initially purified from the chick eye on the basis of its ability to promote survival of E8 chick ciliary ganglion neurons in culture². 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 brain⁴. 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)⁵.

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)^6,7.

CNTF binds to CNTFRα, the latter associates with gp130 which recruits LIFR. This leads to the activation of a signaling cascade involving the JAK/STAT pathway⁷.

CNTFRα 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 CNTF⁸.