Glial cell-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the GDNFgene. 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.
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.
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.
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