Glial cell line-derived neurotrophic factor

GDNF
Gene ontology
Molecular function	protein homodimerization activity protein binding growth factor activity signaling receptor binding chemoattractant activity involved in axon guidance
Cellular component	extracellular region intracellular anatomical structure extracellular space
Biological process	peristalsis ureteric bud development regulation of dopamine uptake involved in synaptic transmission peripheral nervous system development sympathetic nervous system development organ induction adult locomotory behavior positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis regulation of stem cell differentiation regulation of morphogenesis of a branching structure mesenchymal to epithelial transition involved in metanephros morphogenesis negative regulation of apoptotic process nervous system development positive regulation of monooxygenase activity enteric nervous system development mRNA stabilization branching involved in ureteric bud morphogenesis postganglionic parasympathetic fiber development positive regulation of dopamine secretion neural crest cell migration postsynaptic membrane organization positive regulation of cell population proliferation positive regulation of cell differentiation positive regulation of ureteric bud formation ureteric bud formation regulation of gene expression negative regulation of extrinsic apoptotic signaling pathway in absence of ligand metanephros development neuron projection development signal transduction positive regulation of transcription by RNA polymerase II MAPK cascade axon guidance negative regulation of neuron apoptotic process positive regulation of branching involved in ureteric bud morphogenesis regulation of signaling receptor activity dorsal spinal cord development embryonic organ development chemoattraction of axon commissural neuron axon guidance regulation of semaphorin-plexin signaling pathway
Sources:Amigo / QuickGO

Ensembl				ENSG00000168621	ENSMUSG00000022144
UniProt	P39905	P48540
RefSeq (mRNA)	NM_000514 NM_001190468 NM_001190469 NM_001278098 NM_199231 NM_199234	NM_010275 NM_001301332 NM_001301333 NM_001301357
RefSeq (protein)	NP_000505 NP_001177397 NP_001177398 NP_001265027 NP_954701	NP_001288261 NP_001288262 NP_001288286 NP_034405
Location (UCSC)	Chr 5: 37.81 – 37.84 Mb	Chr 15: 7.84 – 7.87 Mb
PubMed search	[3]	[4]

Wikidata

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Glial cell line-derived neurotrophic factor (GDNF) is a

. It is also responsible for the determination of spermatogonia into primary spermatocytes, i.e. it is received by RET proto-oncogene (RET) and by forming gradient with SCF it divides the spermatogonia into two cells. As the result there is retention of spermatogonia and formation of spermatocyte.^{[7][full citation needed]}

GDNF family of ligands (GFL)

GDNF was discovered in 1991,^[8] and is the first member of the GDNF family of ligands (GFL) found.

Function

GDNF is highly distributed throughout both the peripheral and central nervous system. It can be secreted by

The GDNF gene encodes a highly conserved

GDNF has the ability to activate the ERK-1 and ERK-2 isoforms of MAP kinase in sympathetic neurons as well as P13K/AKT pathways via activation of its

The most prominent feature of GDNF is its ability to support the survival of dopaminergic

These neuronal populations die in the course of

Structure

GDNF has a structure that is similar to

Interactions

Glial cell line-derived neurotrophic factor has been shown to

Potential as therapeutics

GDNF has been investigated as a treatment for Parkinson's disease, though early research has not shown a significant effect.[8]^[19] Vitamin D potently induces GDNF expression.^[20]

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.^[21] 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.^[22] 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.^[23]

Neuropsychopharmacology

Administration of the African hallucinogen ibogaine potently increases GDNF expression in the ventral tegmental area, which is the mechanism behind the alkaloid's anti-addictive effect.^[24] Rodent models for a non-psychedelic analogue of this compound show promise in promoting GDNF expression without the hallucinogenic or cardiotoxic effects well documented for ibogaine.^[25]

There is evidence, that Gdnf is an alcohol-responsive

References

Further reading

• Hofstra RM, Osinga J, Buys CH (1998). "Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype". European Journal of Human Genetics. 5 (4): 180–5.
  PMID 9359036
  .
• Martucciello G, Ceccherini I, Lerone M, Jasonni V (July 2000). "Pathogenesis of Hirschsprung's disease". Journal of Pediatric Surgery. 35 (7): 1017–25.
  PMID 10917288
  .
• Schindelhauer D, Schuffenhauer S, Gasser T, Steinkasserer A, Meitinger T (August 1995). "The gene coding for glial cell line derived neurotrophic factor (GDNF) maps to chromosome 5p12-p13.1". Genomics. 28 (3): 605–7.
  PMID 7490108
  .
• Tomac A, Lindqvist E, Lin LF, Ogren SO, Young D, Hoffer BJ, Olson L (January 1995). "Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo". Nature. 373 (6512): 335–9.
  S2CID 4340992
  .
• Oppenheim RW, Houenou LJ, Johnson JE, Lin LF, Li L, Lo AC, et al. (January 1995). "Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF". Nature. 373 (6512): 344–6.
  S2CID 2863274
  .
• Schaar DG, Sieber BA, Sherwood AC, Dean D, Mendoza G, Ramakrishnan L, et al. (December 1994). "Multiple astrocyte transcripts encode nigral trophic factors in rat and human". Experimental Neurology. 130 (2): 387–93.
  S2CID 37574956
  .
• Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F (May 1993). "GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons". Science. 260 (5111): 1130–2.
  PMID 8493557
  .
• Bermingham N, Hillermann R, Gilmour F, Martin JE, Fisher EM (December 1995). "Human glial cell line-derived neurotrophic factor (GDNF) maps to chromosome 5". Human Genetics. 96 (6): 671–3.
  S2CID 30960307
  .
• Gash DM, Zhang Z, Ovadia A, Cass WA, Yi A, Simmerman L, et al. (March 1996). "Functional recovery in parkinsonian monkeys treated with GDNF". Nature. 380 (6571): 252–5.
  S2CID 4313985
  .
• Jing S, Wen D, Yu Y, Holst PL, Luo Y, Fang M, et al. (June 1996). "GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF". Cell. 85 (7): 1113–24.
  S2CID 1724567
  .
• Angrist M, Bolk S, Halushka M, Lapchak PA, Chakravarti A (November 1996). "Germline mutations in glial cell line-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient". Nature Genetics. 14 (3): 341–4.
  S2CID 24350470
  .
• Salomon R, Attié T, Pelet A, Bidaud C, Eng C, Amiel J, et al. (November 1996). "Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease". Nature Genetics. 14 (3): 345–7.
  S2CID 22375940
  .
• Ivanchuk SM, Myers SM, Eng C, Mulligan LM (December 1996). "De novo mutation of GDNF, ligand for the RET/GDNFR-alpha receptor complex, in Hirschsprung disease". Human Molecular Genetics. 5 (12): 2023–6.
  PMID 8968758
  .
• Haniu M, Hui J, Young Y, Le J, Katta V, Lee R, et al. (December 1996). "Glial cell line-derived neurotrophic factor: selective reduction of the intermolecular disulfide linkage and characterization of its disulfide structure". Biochemistry. 35 (51): 16799–805.
  PMID 8988018
  .
• Bär KJ, Facer P, Williams NS, Tam PK, Anand P (April 1997). "Glial-derived neurotrophic factor in human adult and fetal intestine and in Hirschsprung's disease". Gastroenterology. 112 (4): 1381–5.
  PMID 9098026
  .
• Jing S, Yu Y, Fang M, Hu Z, Holst PL, Boone T, et al. (December 1997). "GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family". The Journal of Biological Chemistry. 272 (52): 33111–7.
  PMID 9407096
  .
• Eng C, Myers SM, Kogon MD, Sanicola M, Hession C, Cate RL, Mulligan LM (February 1998). "Genomic structure and chromosomal localization of the human GDNFR-alpha gene". Oncogene. 16 (5): 597–601.
  PMID 9482105
  .
• Amiel J, Salomon R, Attié T, Pelet A, Trang H, Mokhtari M, et al. (March 1998). "Mutations of the RET-GDNF signaling pathway in Ondine's curse". American Journal of Human Genetics. 62 (3): 715–7.
  PMID 9497256
  .
• Yamaguchi Y, Wada T, Suzuki F, Takagi T, Hasegawa J, Handa H (August 1998). "Casein kinase II interacts with the bZIP domains of several transcription factors". Nucleic Acids Research. 26 (16): 3854–61.
  PMID 9685505
  .
• Oo TF, Kholodilov N, Burke RE (June 2003). "Regulation of natural cell death in dopaminergic neurons of the substantia nigra by striatal glial cell line-derived neurotrophic factor in vivo". The Journal of Neuroscience. 23 (12): 5141–8.
  PMID 12832538
  .

External links

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