Ciliary neurotrophic factor

Sleeman MW, Anderson KD, Lambert PD et al (2000) The ciliary neurotrophic factor and its receptor, CNTFRa. Pharm Acta Helv 74 265-272... 

Ciliary neurotrophic factor (CNTF) decreases naturally occurring and axotomy-induced cell death and has been evaluated as a treatment for neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS)... 

FIGURE 27-3 Neurotrophic cytokines and their receptors. Neurotrophic cytokines are related to IL6 and bind to cell surface receptor complexes that share a common structural organization. The four ligands interchangeably employ two distinct receptor subunits, leukemia inhibitory factor receptor 3 (LIF-Rpt) andgpl30, and some employ a ligand-specific a subunit. CNTF-R, ciliary neurotrophic factor CT-fR.cardiotrophin 1 receptor IL6-R, interleukin-6 receptor. 

Clatterbuck, R. E., Price, D. L. and Koliatsos, V. E. Further characterization of the effects of brain-derived neurotrophic factor and ciliary neurotrophic factor on axotomized neonatal and adult mammalian motor neurons. /. Comp Neurol. 342 45-56,1994. 

CNTF ciliary neurotrophic factor fCJD familial Creutzfeldt-Jakob disease... 

Haematopoietins Interleukins 2-7, -9, -13 Granulocyte colony stimulating factor Granulocyte-macrophage colony stimulating factor Leukaemia inhibitory factor Erythropoietin Ciliary neurotrophic factor... 

Ciliary neurotrophic factor and glial cell line-derived neurotrophic factor... 

Ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF) represent the most recently discovered members of the neurotrophic factor family. These, however, display no homology to the neurotrophins previously discussed. 

Neurotrophic factors responsible for neuronal survival, dendritic proliferation, and the activation of the different neurotransmission systems are present in the central nervous system [CNS). The most well-known one is the NGF, a peptidergic complex of 140 kd and with a sedimentation coefficient of 7s. NGF has three subunits, a, p, and y. Subunit p is the active part of the molecule. Other neurotrophic factors [F. ffefti 1994) include 1) brain-derived neurotrophic factor [BDNF), 2) neurotrophin 3, 3) neurotrophin 4/5, and 4) ciliary neurotrophic factor. 

The neurotrophins represent a family of survival and differentiation factors that exert profound effects in the central and peripheral nervous systems. The neurotrophins are currently under investigation as therapeutic agents for the treatment of neurodegenerative disorders and nerve injury either individually or in combination with other trophic factors such as ciliary neurotrophic factor (CNTF) or fibroblast growth factor (FGF). 

Selegiline upregulates ciliary neurotrophic factor (CNF) gene expression in astroglial cell culture. 

Cytokine subfamily 2 includes proteins with heterodimeric a—(3 or ct-gpl30 receptors. Thus, granulocyte macrophage colony stimulating factor (GM-GSF), IL-3 and IL-5 act via a—(3 receptors and share (3 receptors. Cardiotrophin-1 (GT-1), ciliary neurotrophic factor (CTNF), IL-6, IL-1, leukaemia inhibitory factor (LIF) and oncostatin M (OSM) act via heterodimeric a-gpl30 receptors with a shared gpl30 receptor subunit. Leucocyte-derived cytokines of this family have immunomodulatory and haematopoietic effects. 

CT-1, cardiotrophin-1 CTNF, ciliary neurotrophic factor CTP, cytidine 5 -triphosphate Cyclic AMP, adenosine 3, 5 -cyclic monophosphate... 

Knepp, V. M., Whatley, J. L., Muchnik, A., and Calderwood,T. S. (1996), Identification of antioxidants for prevention of peroxide-mediated oxidation of recombinant human ciliary neurotrophic factor and recombinant human nerve growth factor, J. Parenteral Sci. Technol., 50,163-171. 

Fig. 3. The gplSO family of cytokines and receptors. Schematic representation of gpl30 and leukemia inhibitory factor receptor (LIFR) oriented in a cell membrane. Of the four-helix bundle gplSO cytokines, structural information currently exists for human interleukin 6 (IL-6) (green) (Somers et al, 1997), human herpes virus interleukin 6 (HlTV-8 IL-6) (purple) (Chow et al, 2001a), ciliary neurotrophic factor (CNTF) (orange) (McDonald et al., 1995), leukemia inhibitory factor (LIF) (blue) (Robinson et al, 1994), and oncostatin-M (OSM) (red) (Deller et al, 2000). Lower panel is a detailed list of gplSO cytokines and the associated receptors incorporated into the final signaling complex. (See Color Insert.)...

Inoue, M., Nakayama, C., Kikuchi, K., Kimura, T., Ishige, Y, Ito, A., Kanaoka, M., and Noguchi, H. (1995). D1 cap region involved in the receptor recognition and neural cell survival activity of human ciliary neurotrophic factor. Proc. Natl. Acad. Sci. USA 92, 8579-8583. 

McDonald, N. Q., Panayotatos, N., and Hendrickson, W. A. (1995). Grystal structure of dimeric human ciliary neurotrophic factor determined by MAD phasing. EMBO I. 14, 2689-2699. 

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