Glial cell line-derived neurotrophic factor

2V5E, 3FUB, 4UX8266814573ENSG00000168621ENSMUSG00000022144P39905P48540NM_199234NM_010275NM_001301332NM_001301333NM_001301357NP_000505NP_001177397NP_001177398NP_001265027NP_954701NP_001288261NP_001288262NP_001288286NP_034405Glial cell-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the GDNF gene. GDNF is a small protein that potently promotes the survival of many types of neurons. It signals through GFRα receptors, particularly GFRα1.1agq: GLIAL CELL-DERIVED NEUROTROPHIC FACTOR FROM RAT Glial cell-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the GDNF gene. GDNF is a small protein that potently promotes the survival of many types of neurons. It signals through GFRα receptors, particularly GFRα1. This gene encodes a highly conserved neurotrophic factor. The recombinant form of this protein was shown to promote the survival and differentiation of dopaminergic neurons in culture, and was able to prevent apoptosis of motor neurons induced by axotomy. The encoded protein is processed to a mature secreted form that exists as a homodimer. The mature form of the protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. In addition to the transcript encoding GDNF, two additional alternative transcripts encoding distinct proteins, referred to as astrocyte-derived trophic factors, have also been described. Mutations in this gene may be associated with Hirschsprung's disease. The most prominent feature of GDNF is its ability to support the survival of dopaminergic and motorneurons. These neuronal populations die in the course of Parkinson's disease and amyotrophic lateral sclerosis (ALS). GDNF also regulates kidney development and spermatogenesis, and it affects alcohol consumption. GDNF was discovered in 1991, and is the first member of the GDNF family of ligands (GFL) found. Glial cell line-derived neurotrophic factor has been shown to interact with GFRA2 and GDNF family receptor alpha 1. GDNF has been investigated as a treatment for Parkinson's disease, though early research has not shown a significant effect. Vitamin D potently induces GDNF expression. In 2012, the University of Bristol began a five-year clinical trial on Parkinson's sufferers, in which surgeons introduced a port into the skull of each of the 41 participants through which the drug could be delivered, in order to enable it to reach the damaged cells directly. The results of the double-blind trial, where half the participants were randomly assigned to receive regular infusions of GDNF and the other half placebo infusions, did not show a statistically significant difference between the active treatment group and those who received placebo, but did confirm the effects on damaged brain cells. The trial was funded by Parkinson's UK with support from The Cure Parkinson's Trust, whose founder, Tom Isaacs, was one of the participants.