Species Human Entrez 2668 | Human Mouse Ensembl ENSG00000168621 | |
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Aliases GDNF, ATF1, ATF2, HFB1-HSCR3, glial cell derived neurotrophic factor External IDs OMIM: 600837 MGI: 107430 HomoloGene: 433 GeneCards: GDNF | ||
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.
Contents
Function
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 family of ligands (GFL)
GDNF was discovered in 1991, and is the first member of the GDNF family of ligands (GFL) found.
Interactions
Glial cell line-derived neurotrophic factor has been shown to interact with GFRA2 and GDNF family receptor alpha 1.
Potential as therapeutics
GDNF has regenerative properties for brain cells and showed potential as treatment for Parkinson's disease - monkeys with an induced form of Parkinson's disease showed less trembling when treated with the drug, and neuronal fibres grew in part of the human brain exposed to the drug. However progress to a treatment is hampered by the problem of delivering the drug to brain cells through the blood-brain barrier in human.
Vitamin D potently induces GDNF expression.
Exposure of dopaminergic-like cell line to Ibogaine HCl results in an increase in GDNF mRNA, leading to protein expression and to the corresponding activation of the GDNF signaling pathway. This, in turn, leads to a further increase in the mRNA level of the growth factor through a feed-back loop. It was also found that ibogaine metabolite, noribogaine, also possess the ability to increase GDNF levels.