Glial cell line-derived neurotrophic factor

Glial cell derived neurotrophic factor
GDNF structure
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2V5E, 3FUB, 4UX8
Identifiers
Symbols	GDNF ; ATF1; ATF2; HFB1-GDNF; HSCR3
External IDs	OMIM: 600837 MGI: 107430 HomoloGene: 433 GeneCards: GDNF Gene
Gene ontology Molecular function • receptor binding • protein binding • growth factor activity • protein homodimerization activity Cellular component • extracellular region Biological process • metanephros development • branching involved in ureteric bud morphogenesis • neural crest cell migration • organ induction • postsynaptic membrane organization • mesenchymal to epithelial transition involved in metanephros morphogenesis • signal transduction • nervous system development • axon guidance • positive regulation of cell proliferation • adult locomotory behavior • regulation of gene expression • postganglionic parasympathetic fiber development • peristalsis • neuron projection development • positive regulation of monooxygenase activity • positive regulation of dopamine secretion • negative regulation of apoptotic process • negative regulation of neuron apoptotic process • positive regulation of cell differentiation • positive regulation of transcription from RNA polymerase II promoter • mRNA stabilization • enteric nervous system development • sympathetic nervous system development • regulation of dopamine uptake involved in synaptic transmission • ureteric bud formation • regulation of morphogenesis of a branching structure • positive regulation of ureteric bud formation • positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis • positive regulation of branching involved in ureteric bud morphogenesis • regulation of stem cell differentiation • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2668	14573
Ensembl	ENSG00000168621	ENSMUSG00000022144
UniProt	P39905	P48540
RefSeq (mRNA)	NM_000514	NM_001301332
RefSeq (protein)	NP_000505	NP_001288261
Location (UCSC)	Chr 5: 37.81 – 37.84 Mb	Chr 15: 7.81 – 7.84 Mb
PubMed search	[1]	[2]

Glial cell-derived neurotrophic factor, also known as 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.

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.

Ibogaine HCl It was shown that an initial 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 posses the ability to increase GDNF levels. This mechanism may explain ibogaine's success in successfully treating a parkinson's patient of his debilitating symptoms of his facial muscles feeling frozen and having difficulty finding his balance, talking or using his hands.

External links

• Glial Cell Line-Derived Neurotrophic Factor at the US National Library of Medicine Medical Subject Headings (MeSH)