GDNF family receptor complexes are emerging drug targets
- PMID: 17218019
- DOI: 10.1016/j.tips.2006.12.005
GDNF family receptor complexes are emerging drug targets
Abstract
Glial-cell-line-derived neurotrophic factor (GDNF) family ligands (GFLs), which consist of GDNF, neurturin, artemin and persephin, regulate the development and maintenance of the nervous system. GDNF protects and repairs dopamine-containing neurons, which degenerate in Parkinson's disease, and motoneurons, which die in amyotrophic lateral sclerosis. GDNF and neurturin have shown promise in clinical trials of Parkinson's disease, and artemin is currently undergoing clinical trials for chronic pain treatment. However, the delivery of GFLs into the brain through invasive approaches such as neurosurgery, viral vectors or by the use of encapsulated cells is associated with multiple obstacles. The development of small molecules that specifically activate GFL receptors and that can be applied systemically would overcome most of these problems. The unique nature of the GFL receptors, recent progress in elucidation of the 3D structures of GFLs and GFL-receptor complexes and the use of high-throughput screening have resulted in the development of the first small molecules that mimic the effects of the different GFLs.
Similar articles
-
Small Molecules and Peptides Targeting Glial Cell Line-Derived Neurotrophic Factor Receptors for the Treatment of Neurodegeneration.Int J Mol Sci. 2020 Sep 8;21(18):6575. doi: 10.3390/ijms21186575. Int J Mol Sci. 2020. PMID: 32911810 Free PMC article. Review.
-
Functional mapping of receptor specificity domains of glial cell line-derived neurotrophic factor (GDNF) family ligands and production of GFRalpha1 RET-specific agonists.J Biol Chem. 2000 Feb 4;275(5):3412-20. doi: 10.1074/jbc.275.5.3412. J Biol Chem. 2000. PMID: 10652334
-
Glial cell line-derived neurotrophic factors (GFLs) and small molecules targeting RET receptor for the treatment of pain and Parkinson's disease.Cell Tissue Res. 2020 Oct;382(1):147-160. doi: 10.1007/s00441-020-03227-4. Epub 2020 Jun 17. Cell Tissue Res. 2020. PMID: 32556722 Free PMC article. Review.
-
[Glial cell line-derived neurotrophic factor family ligands and their therapeutic potential].Mol Biol (Mosk). 2016 Jul-Aug;50(4):589-598. doi: 10.7868/S0026898416040108. Mol Biol (Mosk). 2016. PMID: 27668599 Russian.
-
Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain.Expert Opin Ther Targets. 2016;20(2):193-208. doi: 10.1517/14728222.2016.1085972. Epub 2015 Sep 7. Expert Opin Ther Targets. 2016. PMID: 26863504 Review.
Cited by
-
Small Molecules and Peptides Targeting Glial Cell Line-Derived Neurotrophic Factor Receptors for the Treatment of Neurodegeneration.Int J Mol Sci. 2020 Sep 8;21(18):6575. doi: 10.3390/ijms21186575. Int J Mol Sci. 2020. PMID: 32911810 Free PMC article. Review.
-
Small-Molecule Ligands as Potential GDNF Family Receptor Agonists.ACS Omega. 2018 Jan 31;3(1):1022-1030. doi: 10.1021/acsomega.7b01932. Epub 2018 Jan 25. ACS Omega. 2018. PMID: 30023796 Free PMC article.
-
Death receptors and caspases but not mitochondria are activated in the GDNF- or BDNF-deprived dopaminergic neurons.J Neurosci. 2008 Jul 23;28(30):7467-75. doi: 10.1523/JNEUROSCI.1877-08.2008. J Neurosci. 2008. PMID: 18650325 Free PMC article.
-
Nigrostriatal rAAV-mediated GDNF overexpression induces robust weight loss in a rat model of age-related obesity.Mol Ther. 2009 Jun;17(6):980-91. doi: 10.1038/mt.2009.45. Epub 2009 Mar 10. Mol Ther. 2009. PMID: 19277011 Free PMC article.
-
Tissue injury and related mediators of pain exacerbation.Curr Neuropharmacol. 2013 Dec;11(6):592-7. doi: 10.2174/1570159X11311060003. Curr Neuropharmacol. 2013. PMID: 24396335 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
