glial cell line derived neurotrophic factor


Summary: The founding member of the glial cell line-derived neurotrophic factor family. It was originally characterized as a NERVE GROWTH FACTOR promoting the survival of MIDBRAIN dopaminergic NEURONS, and it has been studied as a potential treatment for PARKINSON DISEASE.

Top Publications

  1. Lu B, Cebrian C, Chi X, Kuure S, Kuo R, Bates C, et al. Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis. Nat Genet. 2009;41:1295-302 pubmed publisher
    ..Thus, Etv4 and Etv5 are key components of a gene network downstream of Ret that promotes and controls renal branching morphogenesis. ..
  2. Li L, Su Y, Zhao C, Xu Q. Role of Nurr1 and Ret in inducing rat embryonic neural precursors to dopaminergic neurons. Neurol Res. 2009;31:534-40 pubmed publisher
    ..As a cooperator, Ret seems to work together with Nurr1 in the development of DA neurons. ..
  3. Mundt E, Bates M. Genetics of Hirschsprung disease and anorectal malformations. Semin Pediatr Surg. 2010;19:107-17 pubmed publisher
    ..We and others have shown that genetic factors play an important role in the pathogenesis of ARMs, and many mouse genetic models suggest molecular pathways that may be altered in ARMs. ..
  4. Alladi P, Mahadevan A, Shankar S, Raju T, Muthane U. Expression of GDNF receptors GFRalpha1 and RET is preserved in substantia nigra pars compacta of aging Asian Indians. J Chem Neuroanat. 2010;40:43-52 pubmed publisher
    ..The latter possibility explains our earlier observation that the melanized nigral neurons are preserved with age in the Asian Indians. ..
  5. Zhou Q, Boado R, Lu J, Hui E, Pardridge W. Monoclonal antibody-glial-derived neurotrophic factor fusion protein penetrates the blood-brain barrier in the mouse. Drug Metab Dispos. 2010;38:566-72 pubmed publisher
    ..The brain uptake results indicate it is possible to achieve therapeutic elevations of GDNF in mouse brain with intravenous administration of the cTfRMAb-GDNF fusion protein. ..
  6. Zeng F, Watson R, Nash M. Glial cell-derived neurotrophic factor enhances synaptic communication and 5-hydroxytryptamine 3a receptor expression in enteric neurons. Gastroenterology. 2010;138:1491-501 pubmed publisher
    ..It also up-regulates 5-HT(3a)-receptor expression via modulation of Kv channel activity. Up-regulation of Gdnf after gastrointestinal inflammation might play an important role in the pathophysiology of gastrointestinal diseases. ..
  7. Boger H, Granholm A, McGinty J, Middaugh L. A dual-hit animal model for age-related parkinsonism. Prog Neurobiol. 2010;90:217-29 pubmed publisher
    ..The work discussed in this review is consistent with earlier work demonstrating the importance of GDNF for maintenance of DA neurons and also provides a novel model for progressive DA degeneration and motor dysfunction. ..
  8. Ren Z, Zhang Y. Cells therapy for Parkinson's disease--so close and so far away. Sci China C Life Sci. 2009;52:610-4 pubmed publisher
    ..It is likely that future cell replacement will focus on not only ameliorating symptoms of the disease but also trying to slow the progression of the disease by either neuroprotection or restoring the micro-environment in the midbrain. ..
  9. Yang X, Mertens B, Lehtonen E, Vercammen L, Bockstael O, Chtarto A, et al. Reversible neurochemical changes mediated by delayed intrastriatal glial cell line-derived neurotrophic factor gene delivery in a partial Parkinson's disease rat model. J Gene Med. 2009;11:899-912 pubmed publisher
    ..Delayed GDNF gene delivery only transiently improved dopaminergic function. Over the long term, TH was more abundant, but not functional, and the increase was lost when GDNF gene expression was switched off. ..

More Information


  1. Straten G, Eschweiler G, Maetzler W, Laske C, Leyhe T. Glial cell-line derived neurotrophic factor (GDNF) concentrations in cerebrospinal fluid and serum of patients with early Alzheimer's disease and normal controls. J Alzheimers Dis. 2009;18:331-7 pubmed publisher
    ..Decreased serum concentration of GDNF might be related to altered function of the blood brain barrier thus disturbing clearance or facilitating passover of potentially harmful metabolites. ..
  2. Wu H, Tzeng N, Qian L, Wei S, Hu X, Chen S, et al. Novel neuroprotective mechanisms of memantine: increase in neurotrophic factor release from astroglia and anti-inflammation by preventing microglial activation. Neuropsychopharmacology. 2009;34:2344-57 pubmed publisher
  3. Burke R. Intracellular signalling pathways in dopamine cell death and axonal degeneration. Prog Brain Res. 2010;183:79-97 pubmed publisher
    ..These new points of view offer new opportunities for molecular targeting. ..
  4. Tyagi G, Carnes K, Morrow C, Kostereva N, Ekman G, Meling D, et al. Loss of Etv5 decreases proliferation and RET levels in neonatal mouse testicular germ cells and causes an abnormal first wave of spermatogenesis. Biol Reprod. 2009;81:258-66 pubmed publisher
    ..In addition, ETV5 has critical effects on neonatal spermatogonial proliferation, which may involve impaired signaling through the RET receptor. ..
  5. Yoong L, Wan G, Too H. GDNF-induced cell signaling and neurite outgrowths are differentially mediated by GFRalpha1 isoforms. Mol Cell Neurosci. 2009;41:464-73 pubmed publisher
    ..This study demonstrates the hitherto unrecognized roles of GFRalpha1 isoforms in the activation of distinct signaling pathways and in neurite outgrowths. ..
  6. Ebert A, Barber A, Heins B, Svendsen C. Ex vivo delivery of GDNF maintains motor function and prevents neuronal loss in a transgenic mouse model of Huntington's disease. Exp Neurol. 2010;224:155-62 pubmed publisher
    ..Our data show that mNPCs(GDNF) can survive transplantation, secrete GDNF for several weeks and are able to maintain motor function in this model of HD. ..
  7. Garbayo E, Montero Menei C, Ansorena E, Lanciego J, Aymerich M, Blanco Prieto M. Effective GDNF brain delivery using microspheres--a promising strategy for Parkinson's disease. J Control Release. 2009;135:119-26 pubmed publisher
    ..Furthermore, none of the animals developed antibodies against GDNF demonstrating the safety of glycosylated GDNF use. ..
  8. Liu S, Bohl D, Blanchard S, Bacci J, Said G, Heard J. Combination of microsurgery and gene therapy for spinal dorsal root injury repair. Mol Ther. 2009;17:992-1002 pubmed publisher
    ..This combination treatment provides means to reduce disability due to somatosensory defects after brachial plexus injury. ..
  9. Eberling J, Kells A, Pivirotto P, Beyer J, Bringas J, Federoff H, et al. Functional effects of AAV2-GDNF on the dopaminergic nigrostriatal pathway in parkinsonian rhesus monkeys. Hum Gene Ther. 2009;20:511-8 pubmed publisher
    ..Clinical improvement and evidence of functional recovery in the nigrostriatal pathway, and the absence of adverse effects, support the safety of this approach for the delivery of GDNF over a 6-month period. ..
  10. Huang R, Ke W, Liu Y, Wu D, Feng L, Jiang C, et al. Gene therapy using lactoferrin-modified nanoparticles in a rotenone-induced chronic Parkinson model. J Neurol Sci. 2010;290:123-30 pubmed publisher
    ..The findings may have implications for long-term non-invasive gene therapy for neurodegenerative diseases in general. ..
  11. Adler J, Nico L, VandeVord P, Skoff A. Modulation of neuropathic pain by a glial-derived factor. Pain Med. 2009;10:1229-36 pubmed publisher
    ..Our observations suggest new approaches for treating nerve injury that may prove useful in preventing delayed complications that contribute to long-term debility. ..
  12. Saifudeen Z, Dipp S, Stefkova J, Yao X, Lookabaugh S, El Dahr S. p53 regulates metanephric development. J Am Soc Nephrol. 2009;20:2328-37 pubmed publisher
    ..In summary, our data lend support for a restrictive role for p53 activity in UB outgrowth from the WD. ..
  13. Voutilainen M, Bäck S, Pörsti E, Toppinen L, Lindgren L, Lindholm P, et al. Mesencephalic astrocyte-derived neurotrophic factor is neurorestorative in rat model of Parkinson's disease. J Neurosci. 2009;29:9651-9 pubmed publisher
    ..Our results suggest that MANF is readily distributed throughout the striatum and has significant therapeutic potential for the treatment of PD...
  14. Gonzalez Aparicio R, Flores J, Fernandez Espejo E. Antiparkinsonian trophic action of glial cell line-derived neurotrophic factor and transforming growth factor ?1 is enhanced after co-infusion in rats. Exp Neurol. 2010;226:136-47 pubmed publisher
    ..Functional recovery and improvement of TH signal in the nigrostriatal system were long-lasting and sustained, remaining after cessation of trophic infusion...
  15. Garcia N, Santafe M, Tomas M, Lanuza M, Besalduch N, Priego M, et al. The glial cell line-derived neurotrophic factor (GDNF) does not acutely change acetylcholine release in developing and adult neuromuscular junction. Neurosci Lett. 2010;480:127-31 pubmed publisher
    ..Our findings indicate that GDNF (unlike neurotrophins) does not acutely modulate transmitter release during the developmental process of synapse elimination nor as the NMJ matures. ..
  16. Hobbs R, Seandel M, Falciatori I, Rafii S, Pandolfi P. Plzf regulates germline progenitor self-renewal by opposing mTORC1. Cell. 2010;142:468-79 pubmed publisher
  17. Ohishi M, Harada F, Rahman F, Saito I, Kawano Y, Nozawa Inoue K, et al. GDNF expression in terminal schwann cells associated with the periodontal ruffini endings of the rat incisors during nerve regeneration. Anat Rec (Hoboken). 2009;292:1185-91 pubmed publisher
    ..Taken together with our previous and current studies, it appears that the regeneration of the periodontal RE is controlled by multiple neurotrophins in a stage-specific manner. ..
  18. Liu G, Shi J, Lai C, Hong Y, Shin S, Huang H, et al. Peripheral gene transfer of glial cell-derived neurotrophic factor ameliorates neuropathic deficits in diabetic rats. Hum Gene Ther. 2009;20:715-27 pubmed publisher
    ..In summary, peripheral GDNF gene delivery ameliorates the diabetes-induced downregulation of the GDNF signaling complex in the peripheral nervous system and holds promises for treatment of diabetic neuropathy. ..
  19. Pardridge W, Boado R. Pharmacokinetics and safety in rhesus monkeys of a monoclonal antibody-GDNF fusion protein for targeted blood-brain barrier delivery. Pharm Res. 2009;26:2227-36 pubmed publisher
    ..The fusion protein targeting the insulin receptor has a PK profile similar to a classical small molecule. ..
  20. Hantman A, Jessell T. Clarke's column neurons as the focus of a corticospinal corollary circuit. Nat Neurosci. 2010;13:1233-9 pubmed publisher
    ..Together, our genetic, anatomical and physiological results indicate that Clarke's column spinocerebellar neurons nucleate local spinal corollary circuits that are relevant to motor planning and evaluation. ..
  21. Ohta K, Kuno S, Inoue S, Ikeda E, Fujinami A, Ohta M. The effect of dopamine agonists: the expression of GDNF, NGF, and BDNF in cultured mouse astrocytes. J Neurol Sci. 2010;291:12-6 pubmed publisher
    ..Of the dopamine agonists examined, ropinirole produced and secreted more GDNF than a 1.8-fold greater amount of apomorphine, a lesser amount of bromocriptine, or a 2.8-fold greater amount of SKF-38393, which served as the control group. ..
  22. Gil Z, Cavel O, Kelly K, Brader P, Rein A, Gao S, et al. Paracrine regulation of pancreatic cancer cell invasion by peripheral nerves. J Natl Cancer Inst. 2010;102:107-18 pubmed publisher
    ..These data provide evidence for paracrine regulation of pancreatic cancer invasion by nerves, which may have important implications for potential therapy directed against nerve invasion by cancer. ..
  23. Antus B, Barta I, Czebe K, Horvath I, Csiszer E. Analysis of cytokine pattern in exhaled breath condensate of lung transplant recipients with bronchiolitis obliterans syndrome. Inflamm Res. 2010;59:83-6 pubmed
    ..We conclude that inflammatory cytokines are present in EBC of lung transplant recipients, however the potential benefit of detecting the EBC proteome warrants further studies. ..
  24. Frieboes L, Palispis W, Gupta R. Nerve compression activates selective nociceptive pathways and upregulates peripheral sodium channel expression in Schwann cells. J Orthop Res. 2010;28:753-61 pubmed publisher
    ..CNC injury appears to be a unique model of noninflammatory neuropathic pain. Further investigation of the underlying molecular basis could yield promising targets for early diagnosis and treatment. ..
  25. Madhavan L, Daley B, Paumier K, Collier T. Transplantation of subventricular zone neural precursors induces an endogenous precursor cell response in a rat model of Parkinson's disease. J Comp Neurol. 2009;515:102-15 pubmed publisher
  26. Magill C, Moore A, Yan Y, Tong A, MacEwan M, Yee A, et al. The differential effects of pathway- versus target-derived glial cell line-derived neurotrophic factor on peripheral nerve regeneration. J Neurosurg. 2010;113:102-9 pubmed publisher
    ..Treatment with neurotrophic factors such as GDNF may offer new possibilities for the treatment of peripheral nerve injury. ..
  27. Little M, Georgas K, Pennisi D, Wilkinson L. Kidney development: two tales of tubulogenesis. Curr Top Dev Biol. 2010;90:193-229 pubmed publisher
    ..Here we review both what is known and remains to be understood in kidney tubulogenesis. ..
  28. Zhang X, Zhang Z, Sha W, Xie C, Xi G, Zhou H, et al. Electroconvulsive therapy increases glial cell-line derived neurotrophic factor (GDNF) serum levels in patients with drug-resistant depression. Psychiatry Res. 2009;170:273-5 pubmed publisher
    ..No significant increase was seen in non-responders. These results suggest that successful ECT may be associated with elevated serum GDNF levels. ..
  29. Torres E, Monville C, Lowenstein P, Castro M, Dunnett S. Delivery of sonic hedgehog or glial derived neurotrophic factor to dopamine-rich grafts in a rat model of Parkinson's disease using adenoviral vectors Increased yield of dopamine cells is dependent on embryonic donor age. Brain Res Bull. 2005;68:31-41 pubmed
  30. Abe K. [Gene-stem Cell therapy for ischemic stroke]. Brain Nerve. 2009;61:1043-9 pubmed
  31. Nielsen J, Gotfryd K, Li S, Kulahin N, Soroka V, Rasmussen K, et al. Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion molecule (NCAM) interactions in induction of neurite outgrowth and identification of a binding site for NCAM in the heel region of GDNF. J Neurosci. 2009;29:11360-76 pubmed publisher
  32. Wan G, Too H. A specific isoform of glial cell line-derived neurotrophic factor family receptor alpha 1 regulates RhoA expression and glioma cell migration. J Neurochem. 2010;115:759-70 pubmed publisher
    ..Taken together, these unanticipated results indicate that GFR?1b is involved in glioma migration through glial cell line-derived neurotrophic factor -GFR?1b-NCAM signaling complex and modulation of RhoA expression. ..
  33. Ko J, Lee H, Park C, Koh H, Lee Y, Lee S. Conditions for tumor-free and dopamine neuron-enriched grafts after transplanting human ES cell-derived neural precursor cells. Mol Ther. 2009;17:1761-70 pubmed publisher
    ..These findings indicate that hES-NP cell expansion in conjunction with Bcl-XL+SHH transgene expression may provide a renewable and safe source of DA neurons for transplantation in PD. ..
  34. Tee J, Choi Y, Shah M, Dnyanmote A, Sweeney D, Gallegos T, et al. Protein kinase A regulates GDNF/RET-dependent but not GDNF/Ret-independent ureteric bud outgrowth from the Wolffian duct. Dev Biol. 2010;347:337-47 pubmed publisher
  35. Kells A, Eberling J, Su X, Pivirotto P, Bringas J, Hadaczek P, et al. Regeneration of the MPTP-lesioned dopaminergic system after convection-enhanced delivery of AAV2-GDNF. J Neurosci. 2010;30:9567-77 pubmed publisher
    ..Overall, these data demonstrate nonclinical neurorestoration after putaminal infusion of AAV2-GDNF and suggest that clinical investigation in PD patients is warranted. ..
  36. Larkin E, Patel S, Goodloe R, Li Y, Zhu X, Gray McGuire C, et al. A candidate gene study of obstructive sleep apnea in European Americans and African Americans. Am J Respir Crit Care Med. 2010;182:947-53 pubmed publisher
    ..This candidate gene analysis identified the potential role of genes operating through intermediate disease pathways to influence sleep apnea phenotypes, providing a framework for focusing future replication studies. ..
  37. Li J, Chian R, Ay I, Kashi B, Celia S, Tamrazian E, et al. Insect GDNF:TTC fusion protein improves delivery of GDNF to mouse CNS. Biochem Biophys Res Commun. 2009;390:947-51 pubmed publisher
    ..These studies indicate that insect cell-derived GDNF:TTC retains its bi-functional activity in mammalian CNS in vivo and improves delivery of GDNF to spinal cord following intramuscular- or intrathecal administration. ..
  38. Shang J, Deguchi K, Yamashita T, Ohta Y, Zhang H, Morimoto N, et al. Antiapoptotic and antiautophagic effects of glial cell line-derived neurotrophic factor and hepatocyte growth factor after transient middle cerebral artery occlusion in rats. J Neurosci Res. 2010;88:2197-206 pubmed publisher
  39. Hadaczek P, Johnston L, Forsayeth J, Bankiewicz K. Pharmacokinetics and bioactivity of glial cell line-derived factor (GDNF) and neurturin (NTN) infused into the rat brain. Neuropharmacology. 2010;58:1114-21 pubmed publisher
    ..Our data suggest that daily or continuous dosing may not be necessary for delivering growth factors into the CNS. ..
  40. Manfredsson F, Burger C, Rising A, Zuobi Hasona K, Sullivan L, Lewin A, et al. Tight Long-term dynamic doxycycline responsive nigrostriatal GDNF using a single rAAV vector. Mol Ther. 2009;17:1857-67 pubmed publisher
    ..Therefore, this single rAAV vector system meets most of the requirements for an experimental reagent for treatment of PD. ..
  41. Harris W, Sachana M, Flaskos J, Hargreaves A. Neuroprotection from diazinon-induced toxicity in differentiating murine N2a neuroblastoma cells. Neurotoxicology. 2009;30:958-64 pubmed publisher
    ..In conclusion, these data demonstrate that C6 conditioned medium protects N2a cells from the neurite inhibitory effects of diazinon by blocking molecular events leading to axon damage and that GDNF is implicated in these effects. ..
  42. Pedersen L, Jacobsen L, Mollerup S, Gjerstad J. Spinal cord long-term potentiation (LTP) is associated with increased dorsal horn gene expression of IL-1beta, GDNF and iNOS. Eur J Pain. 2010;14:255-60 pubmed publisher
    ..05, HFS vs. control). For the first time we show that spinal cord LTP is associated with an increased dorsal horn expression of the genes for IL-1beta, GDNF and iNOS. ..
  43. Narita N, Tanemura A, Murali R, Scolyer R, Huang S, Arigami T, et al. Functional RET G691S polymorphism in cutaneous malignant melanoma. Oncogene. 2009;28:3058-68 pubmed publisher
    ..The study demonstrates that RETp is frequently found in cutaneous melanoma, particularly desmoplastic subtypes, and responds to GDNF inducing events favorable for tumor progression. ..
  44. Madduri S, Papaloïzos M, Gander B. Synergistic effect of GDNF and NGF on axonal branching and elongation in vitro. Neurosci Res. 2009;65:88-97 pubmed publisher
    ..This information should be relevant for the development of implants containing NTFs and on drug therapy of damaged peripheral nerves. ..
  45. Lee S, Jang M, Kim O, Lee O, Kim N, Yoo K, et al. Activation of the GDNF-inducible transcription factor (GIF) gene promoter by glucocorticoid and progesterone. J Steroid Biochem Mol Biol. 2009;115:30-5 pubmed publisher
    ..These observations demonstrate a molecular basis for glucocorticoid and progesterone-induced up-regulation of GIF gene transcription and provide a mechanism for the modulation of dopamine-mediated behaviors by these hormones. ..
  46. Wang C, Lee W, Ghanta V, Wang W, Cheng S, Hsueh C. Molecules involve in the self-protection of neurons against glucose-oxygen-serum deprivation (GOSD)-induced cell damage. Brain Res Bull. 2009;79:169-76 pubmed publisher
    ..The study provided a useful platform for screening of potential anti-ischemic drugs and also explained why GOSD neuron derived conditioned medium (NCM) only exerted a time-restricted neuroprotection. ..
  47. Carnicella S, Ahmadiantehrani S, Janak P, Ron D. GDNF is an endogenous negative regulator of ethanol-mediated reward and of ethanol consumption after a period of abstinence. Alcohol Clin Exp Res. 2009;33:1012-24 pubmed publisher
    ..Our results suggest that endogenous GDNF negatively regulates the rewarding effect of ethanol and ethanol-drinking behaviors after a period of abstinence. ..
  48. Barras F, Kuntzer T, Zurn A, Pasche P. Local delivery of glial cell line-derived neurotrophic factor improves facial nerve regeneration after late repair. Laryngoscope. 2009;119:846-55 pubmed publisher
    ..GDNF is a potent neurotrophic factor to improve facial nerve regeneration in grafts performed several months after the nerve lesion. However, GDNF should not be used for immediate repair, as it possibly inhibits the nerve regeneration. ..
  49. Fu M, Sato Y, Lyons Warren A, Zhang B, KANE M, Napoli J, et al. Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation. Development. 2010;137:631-40 pubmed publisher
  50. Otoshi K, Kikuchi S, Konno S, Sekiguchi M. The reactions of glial cells and endoneurial macrophages in the dorsal root ganglion and their contribution to pain-related behavior after application of nucleus pulposus onto the nerve root in rats. Spine (Phila Pa 1976). 2010;35:264-71 pubmed publisher
    ..In the recovery phase, persistent expression of GDNF from activated satellite glial cells might play an important role to restore the function of damaged neurons and recover from neuropathic pain. ..
  51. Zhang D, He F, Li T, Pang X, Cui D, Xie Q, et al. Glial-derived neurotrophic factor regulates intestinal epithelial barrier function and inflammation and is therapeutic for murine colitis. J Pathol. 2010;222:213-22 pubmed publisher
    ..GDNF is namely an important mediator of the cross-talk between EGCs and mucosal epithelial cells. GDNF may be a useful therapeutic approach to the treatment of inflammatory bowel disease. ..
  52. Ledda F. Ligand-induced cell adhesion as a new mechanism to promote synapse formation. Cell Adh Migr. 2007;1:137-9 pubmed
    ..In this overview, I summarize the current concepts of synapse formation in the limelight of this new mechanism of ligand-induced cell adhesion. ..
  53. Wang J, Carnicella S, Ahmadiantehrani S, He D, Barak S, Kharazia V, et al. Nucleus accumbens-derived glial cell line-derived neurotrophic factor is a retrograde enhancer of dopaminergic tone in the mesocorticolimbic system. J Neurosci. 2010;30:14502-12 pubmed publisher
    ..Together, these results demonstrate that NAc-produced GDNF serves as a retrograde enhancer that upregulates the activity of the mesocorticolimbic DA system. ..