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About CNTF:
CNTF or Ciliary Neurotrophic factor is found in humans and is encoded by the CNTF gene.
CNTF Mechanism
The actions of the gene have largely been explored through the activity in the nervous system. It is here that it does promote neurotransmitter synthesis as well as neurite outgrowth. This is apparent in particular neural populations including astrocytes. As well as this, it is considered to be a hypothalamic neuropeptide crucial to the survival of oligodendrocytes and neurons.
Due to this, it is believed that it could be crucial in reducing tissue destruction that is present during inflammatory attacks. When the gene is mutated, it also causes neurotrophic factor deficiency.
CNTF Interactions
The Human ciliary neurotrophic factor has been shown, through research to interact with the Interleukin 6 receptor.
CNTF Function
Various studies have found that CNTF could have therapeutic benefits. For instance, in 2001, a study explored the use of CNTF to treat motor neuron disease. The study found that CNTF actually caused high levels of weight loss in subjects. This discovery suggested that CNTF could reduce food intake, while not having the side effects of hunger or stress. As such, it was proposed as a potential treatment option for those who were leptin-resistant. This is due to the fact that it has been suggested that CNTF operates in a similar way to leptin.
There is also a recombinant version of CNTF humans known as Axokine. This is a modified version with a significantly different structure. The altered version is far more potent in vivo and vitro assays. It is believed that both CNTF and Axokine will stimulate nerve cells for survival.
In 1990, it was used to test for the treatment of amyotrophic lateral sclerosis. The research concluded that muscle control was not significantly improved. However, the participants did experience a reduction in appetite.
As such, the drug was put forward as a potential option for the treatment of obesity. That said, this was never commercialised due to the fact that 70% of the subjects experienced a delayed impact and only produced antibodies after three months. It was also suggested that individuals producing antibodies against CNTF would ultimately develop severe side effects.
Another product being developed is NT-501. This is made from human cells that have been modified to secrete CNTF. Studies have found that this product helps reduce photoreceptor degradation, typically found in patients suffering from retinitis pigmentosa.
CNTF Structure
The crystal structure of the human CNTF was determined in research at 2.4 A resolution. This was completed using multi-wavelength anomalous diffraction which was phased from a single Yb3 + ions. Through the structure, we know that CNTF is dimeric. It has a novel anti-parallel arrangement of subunits. This has not typically been found for other cytokines.
The subunit has a double crossover four-helix bundle fold. Here two helices are found to contribute towards the dimer interface. At the same time, two different helices show more pronounced kinks. According to further analysis, the electrostatic surface of CNTF through the kinked helices could contact the CNTF receptor-alpha.