Glial cell line-derived neurotrophic factor

Glial cell-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the GDNF gene.[5] GDNF is a small protein that potently promotes the survival of many types of neurons.[6] It signals through GFRα receptors, particularly GFRα1. It is also responsible for the determination of spermatogonia into primary spermatocytes i.e. It is received by 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. [Scott F. Gilbert]

GDNF
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGDNF, ATF1, ATF2, HFB1-HSCR3, glial cell derived neurotrophic factor, ATF
External IDsOMIM: 600837 MGI: 107430 HomoloGene: 433 GeneCards: GDNF
Gene location (Human)
Chr.Chromosome 5 (human)[1]
Band5p13.2Start37,812,677 bp[1]
End37,840,041 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

2668

14573

Ensembl

ENSG00000168621

ENSMUSG00000022144

UniProt

P39905

P48540

RefSeq (mRNA)

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 MbChr 15: 7.81 – 7.84 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[6]

The most prominent feature of GDNF is its ability to support the survival of dopaminergic[7] 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 has a powerful and rapid negative (ameliorating) effect on alcohol consumption.[8]

GDNF also promotes hair follicle formation and cutaneous wound healing by targeting resident hair follicle stem cells (BSCs) in the bulge compartment. [9]

GDNF family of ligands (GFL)

GDNF was discovered in 1991,[10] 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[11][12] and GDNF family receptor alpha 1.[11][12]

Potential as therapeutics

GDNF has been investigated as a treatment for Parkinson's disease, though early research has not shown a significant effect.[10][13][14] Vitamin D potently induces GDNF expression.[15]

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.[16] 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.[17] 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.[18]

gollark: If your factory is told to make 100K units of winter clothing of any kind they will probably just go for the simplest/easiest one, even if it isn't very useful to have 100K winter coats (extra small) (plain white). Now, you could say "but in capitalism they'll just make the cheapest one", but companies are directly subservient to what consumers actually want and can't get away with that.
gollark: That is why we have the "legal system"./
gollark: With a government.
gollark: Sure they can. Just apply penalties/taxes if you pollute stuff.
gollark: > Tell factories to produce 100K units of winter clothing and give them free choice of a variety of different accepted models.But then you don't know how much stuff each factory will need.

References
  1. GRCh38: Ensembl release 89: ENSG00000168621 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000022144 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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. doi:10.1126/science.8493557. PMID 8493557.
  6. "Entrez Gene: GDNF glial cell derived neurotrophic factor".
  7. Oo TF, Kholodilov N, Burke RE (Jun 2003). "Regulation of natural cell death in dopaminergic neurons of the substantia nigra by striatal glial cell line-derived neurotrophic factor in vivo". Journal of Neuroscience. 23 (12): 5141–8. doi:10.1523/JNEUROSCI.23-12-05141.2003. PMID 12832538.
  8. Carnicella S, Kharazia V, Jeanblanc J, Janak PH, Ron D (Jun 2008). "GDNF is a fast-acting potent inhibitor of alcohol consumption and relapse". Proceedings of the National Academy of Sciences of the United States of America. 105 (23): 8114–9. doi:10.1073/pnas.0711755105. PMC 2423415. PMID 18541917.
  9. Lisse TS, Sharma M, Vishlaghi N, Pullagura SR, Braun RE (Jun 2020). "GDNF Promotes Hair Formation and Cutaneous Wound Healing by Targeting Bulge Stem Cells". NPJ Regenerative Medicine. 5 (13). doi:10.1038/s41536-020-0098-z. PMC 7293257. PMID 32566252.
  10. Vastag B (Aug 2010). "Biotechnology: Crossing the barrier". Nature. 466 (7309): 916–8. doi:10.1038/466916a. PMID 20725015.
  11. Jing S, Yu Y, Fang M, Hu Z, Holst PL, Boone T, Delaney J, Schultz H, Zhou R, Fox GM (Dec 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. doi:10.1074/jbc.272.52.33111. PMID 9407096.
  12. Cik M, Masure S, Lesage AS, Van Der Linden I, Van Gompel P, Pangalos MN, Gordon RD, Leysen JE (Sep 2000). "Binding of GDNF and neurturin to human GDNF family receptor alpha 1 and 2. Influence of cRET and cooperative interactions". The Journal of Biological Chemistry. 275 (36): 27505–12. doi:10.1074/jbc.M000306200. PMID 10829012.
  13. "Intermittent Bilateral Intraputamenal Treatment with GDNF". The Michael J. Fox Foundation for Parkinson's Research | Parkinson's Disease.
  14. Brian Vastag. "Biotechnology: Crossing the barrier". Nature. Springer Nature. Retrieved 2019-03-27.
  15. Eserian JK (July 2013). "Vitamin D as an effective treatment approach for drug abuse and addiction". Journal of Medical Hypotheses and Ideas. 7 (2): 35–39. doi:10.1016/j.jmhi.2013.02.001. Vitamin D is a potent inducer of endogenous GDNF. The most prominent feature of GDNF is its ability to support the survival of dopaminergic neurons.
  16. "The radical drug trial hoping for a miracle Parkinson's cure". BBC News. Retrieved 10 March 2019.
  17. "GDNF clinical trial offers hope of restoring brain cells damaged in Parkinson's". Parkinsons UK. 27 February 2019. Retrieved 10 March 2019.
  18. "Pioneering trial offers hope for restoring brain cells damaged in Parkinson's". University of Bristol. 2019-02-19.

Further reading
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