GDNF was first discovered in 1991. This makes it the first member of the GDNF family of ligands to be found. The protein is encoded in humans by the GDNF gene. The protein is quite small and does seem to promote the survival for various types of neurons. It is responsible for signalling a variety of GFRa receptors including GFRa1.
This protein has been explored as a potential treatment option for those who are suffering from Parkinson's disease. Currently, research has not shown effective results for this but Vitamin D does seem to induce GDNF expression.
One study in 2012 at the University of Bristol involved a five-week trial for individuals suffering from Parkinson 's. Through this study, the drug was provided through a port directly into the skull. This was completed so that the protein could immediately interact with damaged cells without interference. During the blind trail, there was no significant difference between those who received the placebo and those who received GDNF. However, the research did highlight evidence of the impact of Parkinson’s on the human brain.
According to studies the Glial cell line-derived neurotrophic factor does interact with the GDNF family receptor alpha 1 as well as GFRA2. The impact is observed through a range of GDNF concentrations that are largely responsible for biological activity. As such, it has been suggested that it may have an important impact on cRET independent signalling. It also demonstrates that high-affinity binding can only be measured when cRET is found to be present.
The genes are responsible for encoding a highly conserved neurotrophic factor. It is responsible for both the survival and differentiation of dopaminergic neurons through the culture. Furthermore, it can also prevent motor neurons from apoptosis that is caused by axotomy. The protein which is encoded is then developed to a mature secreted, form. This does exist as a homodimer. This form is also a ligand for the product of the rearranged during transfection protooncogene.
As well as the transcript encoding GDNF research has found two other transcripts that encode separate, unique proteins. These are referred to as astrocyte derived factors. It is strongly believed that mutations in the gene could also be connected to Hirschsprung's disease.
One of the most significant features of GDNF is the factor that it has the ability to support the survival of both motor neurons and dopaminergic. Through both Parkinsons and ALS or amyotrophic lateral sclerosis, these populations of neurons do gradually die. This is why treatment options have been explored using GDNF as a primary form of medicine. Another function of GDNF is that it does regulate kidney development and can even impact the consumption of alcohol.
One study investigating the structure of GDNF was held under an acidic condition. During this process, the interchain disulfide bond was cleaved selectively. This revealed that Cys1010 was part of the intermolecular disulfide linkage. Furthermore, there were three other disulfides that were also identified as intramolecular linkages. The disulfide structure that was determined is thought to be incredibly homologous similar to that of transforming growth factor b2.