Ciliary neurotrophic factor

Abstract

Ciliary neurotrophic factor (CNTF) was first identified and partially purified from embryonic chick eye tissues. Subsequently, it was shown that CNTF is also present in large amounts in sciatic nerves of adult rats and rabbits, which led to its final purification and cloning. CNTF is not secreted by the classical secretory pathway involving the endoplasmatic reticulum and Golgi complex, but can be detected in high quantities within the cytoplasm of myelinating Schwann cells and astrocytes using immunohistochemistry. CNTF supports survival and / or differentiation of a variety of neuronal cell types including sensory, sympathetic and motoneurons. Also, nonneuroanl cells, such as oligodendrocytes, microglial cells, liver cells, and skeletal muscle cells, respond to exogenously administered CNTF, both in vitro and in vivo. During development, expression of CNTF is very low, if indeed it is expressed at all, and the phenotype of mice lacking endogenous CNTF, suggesting that CNTF after inactivation of the CNTF gene by homologous recombination suggests that CNTF does not play a crucial role for responsive cells during embryonic development. However, motoneurons are lost postnatally in mice lacking endogenous CNTF, suggesting that CNTF acts physiologically on the maintenance of these cells. The ability of exogenous CNTF to protect against motoneuron loss following lesion or in other animal models indicates that CNTF might be useful in the treatment of human motoneuron disorders, provided appropriate means of administration can be found. 1994 John Wiley & Sons, Inc.

Pericytes, mesenchymal stem cells and their contributions to tissue repair

“…Another cytokine that has been identified to mediate pericyte recruitment in the lung (Liu et al, 2010), retina (Pi et al, 2011) and kidney (Ren et al, 2013) in response to injury is ciliary neurotrophic factor (CNTF). CNTF is a neurotrophic factor which primarily functions in the differentiation, survival and regeneration of neurons (Sendtner et al, 1994). In a study investigating kidney fibrosis, CNTF produced at the site of injury activated a migratory phenotype and recruited pericytes via LRP-6/WNT ligand and JNK-dependent signalling (Ren et al, 2013).…”

Ciliary Neurotrophic Factor Activates Astrocytes, Redistributes Their Glutamate Transporters GLAST and GLT-1 to Raft Microdomains, and Improves Glutamate HandlingIn Vivo

“…Finally, astrocyte response to injury is altered in CNTF-knock out mice, despite compensation by other cytokines (Martin et al, 2003). Therefore, in addition to its well known neuroprotective function (Sendtner et al, 1994;Sleeman et al, 2000), CNTF appears as a potent endogenous activator of astrocytes.…”

Ciliary neurotrophic factor (CNTF) genotype and body composition

“…However, whether endogenous CNTF plays a physiologic role in weight control is questionable, as most studies show that both mice and humans lacking CNTF are not obese. 10,11 While CNTF is present in Schwann cells and astrocytes, 5,6 it is not released into the peripheral circulation under normal conditions 7,8 and, since the predicted human CNTF protein contains no signal peptide, it raises the question of how CNTF would be released. It is possible that CNTF is only released locally under pathological conditions, such as during nerve injury to promote neuronal regeneration.…”

“…For example, Dittrich et al 23 observed uptake of exogenous CNTF into the liver, and other non-neuronal cells are responsive to CNTF. 7 O'Dell et al 12 hypothesized and found that the absence of endogenous CNTF as a result of homozygosity for the CNTF null allele results in a diminished initiation of anorectic pathways, with a consequent increase in body mass in those with the A/A genotype. O'Dell et al 12 reported 10 kg higher weight and 3 kg/m 2 higher BMI in nine older Caucasian men with the A/A genotype compared to those with the G/G genotype (n ¼ 407).…”

“…4 However, it remains unclear if endogenous CNTF has a similar influence on body weight and composition. The expression of endogenous CNTF is restricted to schwann cells and astrocytes, 5,6 and CNTF is not secreted by the classical pathway involving the endoplasmic reticulum and the golgi complex, 7 and consequently does not circulate in the peripheral circulation. 7,8 Takahashi et al 9 described a G-to-A substitution at position À6 of the second exon of the CNTF gene, which leads to a frameshift mutation and a truncated, biologically inactive protein.…”