Recombinant human CNTF protein (Qk063)

Summary

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Ciliary Neurotrophic Factor (CNTF) is a member of the IL-6 family of cytokines which also includes IL-6, IL-11, leukemia inhibitory factor (LIF), and Neuropoieitin [1-4]. It was initially isolated from chicken embryo ciliary neurons [4,5]. CNTF plays a crucial role in developing and maintaining the nervous and optic nervous systems [3,4,6,7]. It promotes the neurogenesis, differentiation, and survival of various neurons such as neural stem cells, sensory neurons, sympathetic neurons, and motor neurons, as well as oligodendrocytes, microglial cells, liver cells, skeletal muscle cells, and retinal cells [3,4,8–11]. Similarly, to LIF, CNTF is considered an inflammatory stimulation mediator with regenerative and axon growth-stimulating effects [12–14].

CNTF is a homodimer with a molecular weight of approximately 22.8 kDa and forms a four-helix bundle structure through hydrophobic interactions between the helices [2]. Each dimer is composed of 200 amino acids[2]. It is expressed by Schwann cells and astrocytes and binds to specific receptor complexes[2,3,15]. The complexes are composed of either the CNTF R alpha receptor subunit or the IL-6 R alpha receptor subunit with the recruitment of the gp130/LIFRβ receptor subunits[16]. This leads to the activation of various signaling pathways which promote cell survival, differentiation, and regeneration: JAK/STAT3 and PI3K/AKT/mTOR pathways[3,4,13,15].

As CNTF regulates neural development, it is used in vitro to initiate neural induction of human induced pluripotent stem cells (hiPSC) and differentiation of neural progenitor and neural stem cells along with IL-6, LIF, and oncostatin M[6,7,10].  CNTF promotes the self-renewal of neural stem cells with or without EGF, the survival of sensory and motor neurons, and neurite outgrowth[2,17,18]. CNTF also favours a cholinergic phenotype in sympathetic neurons[2,19–22].  Furthermore, CNTF can be used to promote the survival, differentiation, and maturation of glial cells such as astrocytes and Schwann cells. For example, Lin et al. showed that CNTF can activate microglia and dendritic-like microglia similarly to IL-6[23]. Also, Krencik and Zhang describe how to differentiate hiPSC-derived neuroepithelial cells into astrocytes using E8 media supplemented with EGF, FGF-2, and CNTF[24]. Finally, Pan et al. used CNTF with neuregulin 1β and dibutyryl cyclic AMP to obtain Schwann cells[22]. In addition, CNTF has also been reported in the culture of retinal cells and adipocytes[11,25–27].

Due to its protective and regenerative role in the nervous system, research on CNTF has been focused on neurodegenerative diseases (amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease) to slow down the disease progression, as well as retinal diseases (retinitis pigmentosa, and macular degeneration)[4,28–31]. CNTF has also been investigated to treat peripheral nerve injuries and chronic inflammatory diseases (multiple sclerosis) to enhance nerve regeneration and promote neurite growth[29]. The therapeutic potential of CNTF is also extended to treat metabolic diseases to regulate the balance of energy metabolism and induce body weight loss[3,4]. Finally, CNTF has been shown to be involved as a negative modulator of invasion processes of prostate cancer in an in vitro model[32].

Technote: CNTF