GDNF-based therapies, GDNF-producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for parkinson's disease

Frontiers in Neuroanatomy

Volumn 9, Issue FEB, 2015, Pages 1-15

  De Tassigny, Xavier D'anglemont ^a   Pascual, Alberto ^a   Lopez Barneo, Jose ^a,b  

^a UNIVERSITY OF SEVILLE   (Spain)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

Author keywords

Dopaminergic system; GDNF; Mouse models; Neurotrophic factors; Nigrostriatal pathway; Parkinson disease; Parvalbumin interneurons; Striatum

Indexed keywords

ADENOVIRUS VECTOR; ALPHA SYNUCLEIN; AMINO ACID DECARBOXYLASE; ARTEMIN; CASPASE 3; CATALASE; CHOLINE ACETYLTRANSFERASE; DOPAMINE TRANSPORTER; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; GLUTATHIONE PEROXIDASE; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORED PROTEIN; HEME OXYGENASE 1; LACTOFERRIN; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE; NEURTURIN; PARAPROTEIN; PARVALBUMIN; PERSEPHIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEASOME; PROTEIN TYROSINE KINASE; REACTIVE OXYGEN METABOLITE; STRESS ACTIVATED PROTEIN KINASE; SUPEROXIDE DISMUTASE; TRANSFERRIN RECEPTOR; TRIMETHOPRIM; TYROSINE 3 MONOOXYGENASE; UNINDEXED DRUG; VESICULAR MONOAMINE TRANSPORTER;

APOPTOSIS; ARTICLE; BLOOD BRAIN BARRIER; CELL METABOLISM; CELL PROLIFERATION; CORPUS STRIATUM; DOPAMINERGIC NERVE CELL; ENZYME LINKED IMMUNOSORBENT ASSAY; GENE TRANSFER; HERPES SIMPLEX VIRUS; HUMAN; IMMUNE RESPONSE; IN SITU HYBRIDIZATION; INTERNEURON; NEUROPHYSIOLOGY; NEUROPROTECTION; NEUROTOXICITY; NIGRONEOSTRIATAL SYSTEM; NONHUMAN; PARKINSON DISEASE; PHASE 2 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIGNAL TRANSDUCTION;

EID: 84923304686     PISSN: 16625129     EISSN: 16625129     Source Type: Journal    
DOI: 10.3389/fnana.2015.00010     Document Type: Article

References (148)

1. Airaksinen, M. S., and Saarma, M. (2002). The GDNF family: signalling, biological functions and therapeutic value. Nat. Rev. Neurosci. 3, 383-394.doi: 10.1038/nrn812
2. Akerud, P., Canals, J. M., Snyder, E. Y., and Arenas, E. (2001). Neuroprotection through delivery of glial cell line-derived neurotrophic factor by neural stem cells in a mouse model ofParkinson’s disease. J. Neurosci.21, 8108-8118.
3. Anastasia, A., de Erausquin, G. A., Wojnacki, J., and Masco, D. H. (2007). Protection of dopaminergic neurons by electroconvulsive shock in an animal model of Parkinson’s disease. J. Neurochem. 103, 1542-1552.doi: 10.1111/j.1471-4159.2007.04856.x
4. Anastasia, A., Wojnacki, J., de Erausquin, G.A., and Masco, D.H.(2011). Glial cell-line derived neurotrophic factor is essential for electroconvulsive shock-induced neuroprotection in an animal model of Parkinson’s disease. Neuroscience 195, 100-111.doi: 10.1016/j.neuroscience.2011.08.019
5. Bar-Am, O., Weinreb, O., Amit, T., and Youdim, M. B. H. (2005). Regulation of Bcl-2 family proteins, neurotrophic factors and APP processing in the neurorescue activity of propargylamine. FASEBJ. 19,1899-1901.doi: 10.1096/fj.05-3794fje
6. Battaglia, G., Molinaro, G., Riozzi, B., Storto, M., Busceti, C. L., Spinsanti, P., et al. (2009). Activation of mGlu3 receptors stimulates the production of GDNF in striatal neurons. PLoS One 4:e6591.doi: 10.1371/journal.pone.0006591
7. Beck, K.D., Valverde, J., Alexi, T., Poulsen, K., Moffat, B., Vandlen, R. A., et al. (1995). Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain. Nature 373, 339-341.doi: 10.1038/373339a0
8. Bespalov, M.M., and Saarma, M. (2007). GDNF family receptor complexes are emerging drug targets. Trends Pharmacol. Sci.28, 68-74.doi: 10.1016/j.tips.2006.12.005
9. Bizon, J. L., Lauterborn, J. C., and Gall, C. M. (1999). Subpopulations of striatal interneurons can be distinguished on the basis of neurotrophic factor expression. J. Comp. Neurol. 408, 283-298.doi: 10.1002/(sici)1096-9861(19990531)408:2<283::aid-cne9>3.3.co;2-u
10. Boado, R. J., and Pardridge, W. M. (2009). Comparison of blood-brain barrier transport of glial-derived neurotrophic factor (GDNF) and an IgG-GDNF fusion protein in the Rhesus monkey. Drug Metab. Dispos. 37, 2299-2304.doi: 10.1124/dmd.109.028787
11. Boger, H. A., Middaugh, L. D., Huang, P., Zaman, V., Smith, A. C., Hoffer, B. J., et al. (2006). A partial GDNF depletion leads to earlier age-related deterioration of motor function and tyrosine hydroxylase expression in the substantia nigra. Exp. Neurol.202, 336-347.doi: 10.1016/j.expneurol.2006.06.006
12. Boger, H. A., Middaugh, L. D., Zaman, V., Hoffer, B., and Granholm, A.-C. (2008). Differential effects of the dopamine neurotoxin MPTP in animals with a partial deletion of the GDNF receptor, GFR alpha1, gene. Brain Res. 1241, 18-28.doi: 10.1016/j.brainres.2008.09.011
13. Buytaert-Hoefen, K. A., Alvarez, E., and Freed, C. R. (2004). Generation of tyrosine hydroxylase positive neurons from human embryonic stem cells after coculture with cellular substrates and exposure to GDNF. Stem Cells 22, 669-674.doi: 10.1634/stemcells.22-5-669
14. Campos, F. L., Cristovao, A. C., Rocha, S. M., Fonseca, C. P., and Baltazar, G. (2012). GDNF contributes to oestrogen-mediated protection ofmidbrain dopaminergic neurones. J. Neuroendocrinol.24, 1386-1397.doi: 10.1111/j.1365-2826.2012.02348.x
15. Cao, J.P., Wang, H. J., Yu, J. K., Liu, H. M., and Gao, D. S. (2008). The involvement of NF-kappaB p65/p52 in the effects of GDNF on DA neurons in early PD rats. Brain Res. Bull. 76, 505-511.doi: 10.1016/j.brainresbull.2008.03.007
16. Carnicella, S., He, D.-Y., Yowell, Q. V., Glick, S. D., and Ron, D. (2010). Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration. Addict. Biol. 15, 424-433.doi: 10.1111/j.1369-1600.2010.00251.x
17. Cass, W. A., and Peters, L. E. (2010). Neurturin effects on nigrostriatal dopamine release and content: comparison with GDNF. Neurochem. Res. 35, 727-734.doi: 10.1007/s11064-010-0128-0
18. Chang, H. T., and Kita, H. (1992). Interneurons in the rat striatum: relationships between parvalbumin neurons and cholinergic neurons. Brain Res. 574, 307-311.doi: 10.1016/0006-8993(92)90830-3
19. Chao, C. C., Chiang, C. H., Ma, Y. L., and Lee, E. H. Y. (2006). Molecular mechanism of the neurotrophic effect of GDNF on DA neurons: role of protein kinase CK2. Neurobiol. Aging 27, 105-118.doi: 10.1016/j.neurobiolaging.2005.01.009
20. Chao, C.C., and Lee, E. H. (1999). Neuroprotective mechanism of glial cell line-derived neurotrophic factor on dopamine neurons: role of antioxidation. Neuropharmacology 38, 913-916.doi: 10.1016/s0028-3908(99)00030-1
21. Chauhan, N. B., Siegel, G. J., and Lee, J. M. (2001). Depletion of glial cell line-derived neurotrophic factor in substantia nigra neurons of Parkinson’s disease brain. J. Chem.Neuroanat.21, 277-288.doi: 10.1016/s0891-0618(01)00115-6
22. Chen, P.-S., Peng, G.-S., Li, G., Yang, S., Wu, X., Wang, C.-C., et al. (2006). Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes. Mol. Psychiatry 11, 1116-1125.doi: 10.1038/sj.mp.4001893
23. Choi-Lundberg, D., Lin, Q., Chang, Y., Chiang, Y., Hay, C., Mohajeri, H., et al.(1997). Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 275, 838-841.doi: 10.1126/science.275.5301.838
24. Cohen, A. D., Tillerson, J. L., Smith, A. D., Schallert, T., and Zigmond, M. J. (2003). Neuroprotective effects of prior limb use in 6-hydroxydopamine-treated rats: possible role of GDNF. J. Neurochem. 85, 299-305.doi: 10.1046/j.1471-4159.2003.01657.x
25. Cunningham, L. A., and Su, C. (2002). Astrocyte delivery of glial cell line-derived neurotrophic factor in a mouse model of Parkinson’s disease. Exp. Neurol. 174, 230-242.doi: 10.1006/exnr.2002.7877
26. de Lau, L. M. L., and Breteler, M. M. B. (2006). EpidemiologyofParkinson disease. LancetNeurol. 5, 525-535.doi: 10.1016/S1474-4422(06)70471-9
27. Dezawa, M., Kanno, H., Hoshino, M., Cho, H., Matsumoto, N., Itokazu, Y., et al. (2004). Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J. Clin. Invest. 113, 1701-1710.doi: 10.1172/jci200420935
28. Di Liberto, V., Mudo, G., and Belluardo, N. (2011). mGluR2/3 agonist LY379268, by enhancing the production of GDNF, induces a time-related phosphorylation of RET receptor and intracellular signaling Erk1/2 in mouse striatum. Neuropharmacology 61, 638-645.doi: 10.1016/j.neuropharm.2011.05.006
29. Du, Y., Li, X., Yang, D., Zhang, X., Chen, S., Huang, K., et al. (2008). Multiple molecular pathways are involved in the neuroprotection of GDNF against proteasome inhibitor induced dopamine neuron degeneration in vivo. Exp. Biol. Med. (Maywood) 233, 881-890.doi: 10.3181/0712-rm-329
30. Encinas, M., Tansey, M. G., Tsui-Pierchala, B. A., Comella, J. X., Milbrandt, J., and Johnson, E. M. (2001). c-Src is required for glial cell line-derived neurotrophic factor (GDNF) family ligand-mediated neuronal survival via a phosphatidylinositol-3 kinase (PI-3K)-dependent pathway. J. Neurosci.21, 1464-1472.
31. Espejo, E. F., Montoro, R. J., Armengol, J. A., and Lopez-Barneo, J. (1998). Cellular and functional recovery of parkinsonian rats after intrastriatal transplantation of carotid body cell aggregates. Neuron 20, 197-206.doi: 10.1016/s0896-6273(00)80449-3
32. Francardo, V., Bez, F., Wieloch, T., Nissbrandt, H., Ruscher, K., and Cenci, M. A.. Pharmacological stimulation ofsigma-1 receptors has neurorestorative effects in experimental parkinsonism. Brain 137, 1998-2014.doi: 10.1093/brain/awu107
33. Fu, A., Zhou, Q.-H., Hui, E. K.-W., Lu, J. Z., Boado, R. J., and Pardridge, W. M.. Intravenous treatment of experimental Parkinson’s disease in the mouse with an IgG-GDNF fusion protein that penetrates the blood-brain barrier. Brain Res. 1352,208-213.doi: 10.1016/j.brainres.2010.06.059
34. Fukuda, T. (2009). Network architecture of gap junction-coupled neuronal linkage in the striatum. J. Neurosci.29, 1235-1243.doi: 10.1523/jneurosci.4418-08.2009
35. Garbayo, E., Montero-Menei, C. N., Ansorena, E., Lanciego, J. L., Aymerich, M. S., and Blanco-Prieto, M. J. (2009). Effective GDNF brain delivery using microspheres—a promising strategy for Parkinson’s disease. J. Control. Release 135, 119-126.doi: 10.1016/j.jconrel.2008.12.010
36. Gash, D. M., Zhang, Z., Ovadia, A., Cass, W. A., Yi, A., Simmerman, L., et al. (1996). Functional recovery in parkinsonian monkeys treated with GDNF. Nature 380, 252-255.doi: 10.1038/380252a0
37. Georgievska, B., Jakobsson, J., Persson, E., Ericson, C., Kirik, D., and Lundberg, C. (2004). Regulated delivery of glial cell line-derived neurotrophic factor into rat striatum, using a tetracycline-dependent lentiviral vector. Hum. Gene Ther. 10, 934-944.doi: 10.1089/hum.2004.15.934
38. Gill, S. S., Patel, N. K., Hotton, G. R., O’Sullivan, K., McCarter, R., Bunnage, M., et al. (2003). Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat. Med. 9, 589-595.doi: 10.1038/nm850
39. Golden, J. P., DeMaro, J. A., Osborne, P. A., Milbrandt, J., and Johnson, E. M.. Expression of neurturin, GDNF and GDNF family-receptor mRNA in the developing and mature mouse. Exp. Neurol. 158, 504-528.doi: 10.1006/exnr. 1999.7127
40. Gomes, C. A. R. V., Simoes, P. F., Canas, P. M., Quiroz, C., Sebastiao, A. M., Ferre, S., et al. (2009). GDNF control of the glutamatergic cortico-striatal pathway requires tonic activation of adenosine A receptors. J. Neurochem. 108, 1208-1219.doi: 10.1111/j.1471-4159.2009.05876.x
41. Gomes, C. A. R. V., Vaz, S. H., Ribeiro, J. A., and Sebastiao, A. M. (2006). Glial cell line-derived neurotrophic factor (GDNF) enhances dopamine release from striatal nerve endings in an adenosine A2A receptor-dependent manner. Brain Res. 1113, 129-136.doi: 10.1016/j.brainres.2006.07.025
42. Gonzalez-Barrios, J. A., Lindahl, M., Bannon, M. J., Anaya-Martinez, V., Flores, Navarro-Quiroga, I., et al. (2006). Neurotensin polyplex as an efficient carrier for delivering the human GDNF gene into nigral dopamine neurons of hemiparkinsonian rats. Mol. Ther. 14, 857-865.doi: 10.1016/j.ymthe.2006. 09.001
43. Gonzalez-Reyes, L. E., Verbitsky, M., Blesa, J., Jackson-Lewis, V., Paredes, D., Tillack, K., et al. (2012). Sonic hedgehog maintains cellular and neurochemical homeostasis in the adult nigrostriatal circuit. Neuron 75, 306-319.doi: 10.1016/j.neuron.2012.05.018
44. Granholm, A.-C., Zaman, V., Godbee, J., Smith, M., Ramadan, R., Umphlet, C., et al. (2011). Prenatal LPS increases inflammation in the substantia nigra of Gdnf heterozygous mice. Brain Pathol.21, 330-348.doi: 10.1111/j.1750-3639.2010.00457.x
45. Harrison, I. F., and Dexter, D. T. (2013). Epigenetic targeting ofhistone deacetylase: therapeutic potential in Parkinson’s disease? Pharmacol. Ther. 140, 34-52.doi: 10.1016/j.pharmthera.2013.05.010
46. He, D.-Y., McGough, N. N. H., Ravindranathan, A., Jeanblanc, J., Logrip, M. L., Phamluong, K., et al. (2005). Glial cell line-derived neurotrophic factor mediates the desirable actions of the anti-addiction drug ibogaine against alcohol consumption. J. Neurosci.25, 619-628.doi: 10.1523/jneurosci.3959-04.2005
47. Hebert, M., Van Horne, C., Hoffer, B., and Gerhardt, G. (1996). Functional effects of GDNF in normal rat striatum: presynaptic studies using in vivo electrochemistry and microdialysis. J. Pharmacol. Exp. Ther.279, 1181-1190.
48. Herran, E., Ruiz-Ortega, J. A., Aristieta, A., Igartua, M., Requejo, C., Lafuente, J. V., et al. (2013). In vivo administration of VEGF-and GDNF-releasing biodegradable polymeric microspheres in a severe lesion model ofParkinson’s disease. Eur. J. Pharm. Biopharm. 85, 1183-1190.doi: 10.1016/j.ejpb.2013. 03.034
49. Hidalgo-Figueroa, M., Bonilla, S., Gutierrez, F., Pascual, A., and Lopez-Barneo, J. (2012). GDNF is predominantly expressed in the PV+ neostriatal interneuronal ensemble in normal mouse and after injury of the nigrostriatal pathway. J. Neurosci. 32, 864-872.doi: 10.1523/jneurosci.2693-11.2012
50. Hisaoka, K., Nishida, A., Koda, T., Miyata, M., Zensho, H., Morinobu, S., et al. (2001). Antidepressant drug treatments induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells. J. Neurochem. 79, 25-34.doi: 10.1046/j.1471-4159.2001. 00531.x
51. Hisaoka, K., Nishida, A., Takebayashi, M., Koda, T., Yamawaki, S., and Nakata, Y. (2004). Serotonin increases glial cell line-derived neurotrophic factor release in rat C6 glioblastoma cells. Brain Res. 1002, 167-170.doi: 10.1016/j.brainres.2004. 01.009
52. Hoffer, B.J., Hoffman, A., Bowenkamp, K., Huettl, P., Hudson, J., Martin, D., et al. (1994). Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo. Neurosci. Lett. 182,107-111.doi: 10.1016/0304-3940(94)90218-6
53. Hong, Z., Liu, J., Xia, L., Pan, J., Xiao, Q., Lu, G., et al. (2009). Identification of glial-cell-line-derived neurotrophic factor-regulated proteins of striatum in mouse model ofParkinson disease. Proteomics. Clin. Appl. 3, 1072-1083.doi: 10.1002/prca.200800234
54. Howe, C.L., and Mobley, W. C. (2005). Long-distance retrograde neurotrophic signaling. Curr. Opin. Neurobiol. 15, 40-48.doi: 10.1016/j.conb.2005. 01.010
55. Huang, R., Han, L., Li, J., Ren, F., Ke, W., Jiang, C., et al. (2009). Neuroprotection in a 6-hydroxydopamine-lesioned Parkinson model using lactoferrin-modified nanoparticles. J. GeneMed. 11, 754-763.doi: 10.1002/jgm.1361
56. Ibanez, C. F. (2007). Message in a bottle: long-range retrograde signaling in the nervous system. Trends Cell Biol. 17, 519-528.doi: 10.1016/j.tcb.2007. 09.003
57. Jollivet, C., Aubert-Pouessel, A., Clavreul, A., Venier-Julienne, M.-C., Montero-Menei, C. N., Benoit, J.-P., et al. (2004b). Long-term effect of intra-striatal glial cell line-derived neurotrophic factor-releasing microspheres in a partial rat model ofParkinson’s disease. Neurosci. Lett. 356, 207-210.doi: 10.1016/j.neulet.2003.11.051
58. Jollivet, C., Aubert-Pouessel, A., Clavreul, A., Venier-Julienne, M., Remy, S., Montero-Menei, C., et al. (2004a). Striatal implantation of GDNF releasing biodegradable microspheres promotes recovery of motor function in a partial model of Parkinson’s disease. Biomaterials 25, 933-942.doi: 10.1016/s0142-9612(03)00601-x
59. Jung, U. J., Leem, E., andKim, S. R. (2014). Naringin: aprotector ofthe nigrostriatal dopaminergic projection. Exp. Neurobiol.23, 124-129.doi: 10.5607/en.2014.23.2.124
60. Kauhausen, J., Thompson, L. H., and Parish, C. L. (2013). Cell intrinsic and extrinsic factors contribute to enhance neural circuit reconstruction following transplantation in Parkinsonian mice. J. Physiol. 591, 77-91.doi: 10.1113/jphysiol.2012.243063
61. Kirik, D., Georgievska, B., and Bjorklund, A. (2004). Localized striatal delivery of GDNF as a treatment for Parkinson disease. Nat. Neurosci. 7, 105-110.doi: 10.1038/nn1175
62. Kirik, D., Rosenblad, C., Bjo, A., and Mandel, R. J. (2000). Long-Term rAAV-mediated gene transfer of GDNF in the rat Parkinson’s model: intrastriatal but not intranigral transduction promotes functional regeneration in the lesioned nigrostriatal system. J. Neurosci.20, 4686-4700.
63. Kordower, J. H., and Bjorklund, A. (2013). Trophic factor gene therapy for Parkinson’s disease. Mov. Disord.28, 96-109.doi: 10.1002/mds.25344
64. Kramer, E. R., Aron, L., Ramakers, G. M. J., Seitz, S., Zhuang, X., Beyer, K., et al. (2007). Absence of Ret signaling in mice causes progressive and late degeneration of the nigrostriatal system. PLoS Biol. 5:e39.doi: 10.1371/journal. pbio.0050039
65. Laganiere, J., Kells, A. P., Lai, J. T., Guschin, D., Paschon, D. E., Meng, X., et al.An engineered zinc finger protein activator of the endogenous glial cell line-derived neurotrophic factor gene provides functional neuroprotection in a rat model of Parkinson’s disease. J. Neurosci. 30, 16469-16474.doi: 10.1523/jneurosci.2440-10.2010
66. Lang, A. E., Gill, S., Patel, N. K., Lozano, A., Nutt, J. G., Penn, R., et al.. Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease. Ann. Neurol. 59, 459-466.doi: 10.1002/ana.20737
67. Lau, Y.-S., Patki, G., Das-Panja, K., Le, W.-D., and Ahmad, S. O. (2011). Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson’s disease with moderate neurodegeneration. Eur. J. Neurosci. 33, 1264-1274.doi: 10.1111/j.1460-9568.2011.07626.x
68. Lee, J. Y., Kim, S. H., Ko, A.-R., Lee, J. S., Yu, J. H., Seo, J. H., et al. (2013). Therapeutic effects of repetitive transcranial magnetic stimulation in an animal model ofParkinson’s disease. Brain Res. 1537, 290-302.doi: 10.1016/j.brainres.2013.08.051
69. Leem, E., Nam, J. H., Jeon, M.-T., Shin, W.-H., Won, S.-Y., Park, S.-J., et al. (2014). Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson’s disease. J. Nutr. Biochem.25, 801-806.doi: 10.1016/j.jnutbio.2014.03.006
70. Lei, Z., Jiang, Y., Li, T., Zhu, J., and Zeng, S. (2011). Signaling of glial cell line-derived neurotrophic factor and its receptor GFRa1 induce Nurr1 and Pitx3 to promote survival of grafted midbrain-derived neural stem cells in a rat model of Parkinson disease. J. Neuropathol. Exp. Neurol. 70, 736-747.doi: 10.1097/nen. 0b013e31822830e5
71. Li, X., Peng, C., Li, L., Ming, M., Yang, D., and Le, W. (2007). Glial cell-derived neurotrophic factor protects against proteasome inhibition-induced dopamine neuron degeneration by suppression of endoplasmic reticulum stress and caspase-3 activation. J. Gerontol. A Biol. Sci. Med. Sci. 62, 943-950.doi: 10.1093/gerona/62.9.943
72. Lin, H. F., Doherty, D. H., Lile, J. D., Bektesh, S., and Collins, F. (1993). GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260, 1130-1132.doi: 10.1126/science.8493557
73. Lindvall, O., and Wahlberg, L. U. (2008). Encapsulated cell biodelivery of GDNF: a novel clinical strategy for neuroprotection and neuroregeneration in Parkinson’s disease? Exp. Neurol.209, 82-88.doi: 10.1016/j.expneurol.2007. 08.019
74. Lo Bianco, C., Deglon, N., Pralong, W., and Aebischer, P. (2004). Lentiviral nigral delivery of GDNF does not prevent neurodegeneration in a genetic rat model of Parkinson’s disease. Neurobiol. Dis. 17, 283-289.doi: 10.1016/j.nbd.2004. 06.008
75. Lo Bianco, C., Ridet, J. L., Schneider, B. L., Deglon, N., and Aebischer, P. (2002). Alpha-Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson’s disease. Proc. Natl. Acad. Sci. USA 99, 10813-10818.doi: 10.1073/pnas.152339799
76. Lonka-Nevalaita, L., Lume, M., Leppanen, S., Jokitalo, E., Peranen, J., and Saarma, M. (2010). Characterization of the intracellular localization, processing and secretion of two glial cell line-derived neurotrophic factor splice isoforms. J. Neurosci. 30, 11403-11413.doi: 10.1523/jneurosci.5888-09.2010
77. Lopez-Barneo, J., Pardal, R., Montoro, R. J., Smani, T., Garcia-Hirschfeld, J., and Urena, J. (1999). K+ and Ca 2+ channel activity and cytosolic [Ca 2+] in oxygen-sensing tissues. Respir. Physiol. 115, 215-227.doi: 10.1016/s0034-5687(99)00016-x
78. Love, S., Plaha, P., Patel, N., Hotton, G., Brooks, D., and Gill, S. (2005). Glial cell line-derived neurotrophic factor induces neuronal sprouting in human brain. Nat. Med. 11, 703-704.doi: 10.1038/nm0705-703
79. Marco, S., Saura, J., Perez-Navarro, E., Jose Marti, M., Tolosa, E., and Alberch, J.. Regulation of c-Ret, GFRalpha1 and GFRalpha2 in the substantia nigra pars compacta in a rat model of Parkinson’s disease. J. Neurobiol. 52, 343-351.doi: 10.1002/neu.10082
80. Maruyama, W., Nitta, A., Shamoto-Nagai, M., Hirata, Y., Akao, Y., Yodim, M., et al. (2004). N-Propargyl-1 (R)-aminoindan, rasagiline, increases glial cell line-derived neurotrophic factor (GDNF) in neuroblastoma SH-SY5Y cells through activation of NF-kB transcription factor. Neurochem. Int. 44, 393-400.doi: 10.1016/j.neuint.2003.08.005
81. Maswood, N., Young, J., Tilmont, E., Zhang, Z., Gash, D. M., Gerhardt, G. A., et al. (2004). Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson’s disease. Proc. Natl. Acad. Sci. USA 101, 18171-18176.doi: 10.1073/pnas.0405 831102
82. Mendez, I., Dagher, A., Hong, M., Hebb, A., Gaudet, P., Law, A., et al. (2000). Enhancement of survival of stored dopaminergic cells and promotion of graft survival by exposure of human fetal nigral tissue to glial cell line—derived neurotrophic factor in patients with Parkinson’s disease report of two cases and technical considerations. J. Neurosurg. 92, 863-869.doi: 10.3171/jns.2000.92.5. 0863
83. Migliore, M. M., Ortiz, R., Dye, S., Campbell, R. B., Amiji, M. M., and Waszczak, L. (2014). Neurotrophic and neuroprotective efficacy of intranasal GDNF in a rat model of Parkinson’s disease. Neuroscience 274, 11-23.doi: 10.1016/j.neuroscience.2014.05.019
84. Minguez-Castellanos, A., Escamilla-Sevilla, F., Hotton, G. R., Toledo-Aral, J. J., Ortega-Moreno, A., Mendez-Ferrer, S., et al. (2007). Carotid body autotransplantation in Parkinson disease: a clinical and positron emission tomography study. J. Neurol. Neurosurg. Psychiatry 78, 825-831.doi: 10.1136/jnnp.2006.106021
85. Mizuta, I., Ohta, M., Ohta, K., Nishimura, M., Mizuta, E., Hayashi, K., et al. (2000). Selegiline and desmethylselegiline stimulate NGF, BDNF and GDNF synthesis in cultured mouse astrocytes. Biochem. Biophys. Res. Commun.279, 751-755.doi: 10.1006/bbrc.2000.4037
86. Mogi, M., Togari, A., Kondo, T., Mizuno, Y., Kogure, O., Kuno, S., et al. (2001). Glial cell line-derived neurotrophic factor in the substantia nigra from control and parkinsonian brains. Neurosci. Lett. 300, 179-181.doi: 10.1016/s0304-3940(01)01577-4
87. Monville, C., Torres, E., Thomas, E., Scarpini, C. G., Muhith, J., Lewis, J., et al.. HSV vector-delivery of GDNF in a rat model of PD: partial efficacy obscured by vector toxicity. Brain Res. 1024, 1-15.doi: 10.1016/j.brainres.2004. 06.082
88. Moore, M., Klein, R., Farinas, I., Sauer, H., Armanini, M., Phillips, H., et al. (1996). Renal and neuronal abnormalities in mice lacking GDNF. Nature 382, 76-79.doi: 10.1038/382076a0
89. Munoz-Manchado, A. B., Villadiego, J., Suarez-Luna, N., Bermejo-Navas, A., Garrido-Gil, P., Labandeira-Garcia, J. L., et al. (2013). Neuroprotective and reparative effects of carotid body grafts in a chronic MPTP model of Parkinson’s disease. Neurobiol. Aging 34, 902-915.doi: 10.1016/j.neurobiolaging.2012. 06.001
90. Nakagawa, T., and Schwartz, J. P. (2004). Gene expression profiles of reactive astrocytes in dopamine-depleted striatum. Brain Pathol. 14, 275-280.doi: 10.1111/j.1750-3639.2004.tb00064.x
91. Nakajima, K., Hida, H., Shimano, Y., Fujimoto, I., Hashitani, T., Kumazaki, M., et al. (2001). GDNF is a major component of trophic activity in DA-depleted striatum for survival and neurite extension of DAergic neurons. Brain Res. 916, 76-84.doi: 10.1016/s0006-8993(01)02866-9
92. Newburn, E. N., Duchemin, A.-M., Neff, N. H., and Hadjiconstantinou, M. (2014). GM1 ganglioside enhances Ret signaling in striatum. J. Neurochem. 130, 541-554.doi: 10.1111/jnc.12760
93. Nosrat, C. A., Tomac, A., Lindqvist, E., Lindskog, S., Humpel, C., Stromberg, I., et al. (1996). Cellular expression of GDNF mRNA suggests multiple functions inside and outside the nervous system. Cell Tissue Res.286, 191-207.doi: 10.1007/s004410050688
94. Nutt, J. G., Burchiel, K. J., Comella, C. L., Jankovic, J., Lang, A. E., Laws, E. R. Jr., et al. (2003). Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology 60, 69-73.doi: 10.1212/wnl.60.1.69
95. Ohshima-Hosoyama, S., Simmons, H. A., Goecks, N., Joers, V., Swanson, C. R., Bondarenko, V., et al. (2012). A monoclonal antibody-GDNF fusion protein is not neuroprotective and is associated with proliferative pancreatic lesions in parkinsonian monkeys. PLoS One 7:e39036.doi: 10.1371/journal.pone. 0039036
96. Onyango, I. G., Tuttle, J. B., and Bennett, J. P. Jr. (2005). Brain-derived growth factor and glial cell line-derived growth factor use distinct intracellular signaling pathways to protect PD cybrids from H2O2-induced neuronal death. Neurobiol. Dis.20, 141-154.doi: 10.1016/j.nbd.2005.02.009
97. Oppenheim, R. W., Houenou, L. J., Johnson, J. E., Lin, L. F., Li, L., Lo, A. C., et al. (1995). Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF. Nature 373, 344-346.doi: 10.1038/37 3344a0
98. Palfi, S., Leventhal, L., Chu, Y., Ma, S. Y., Emborg, M., Bakay, R., et al. (2002). Lentivirally delivered glial cell line-derived neurotrophic factor increases the number of striatal dopaminergic neurons in primate models of nigrostriatal degeneration. J. Neurosci.22, 4942-4954.
99. Pallini, R., Consales, A., Lauretti, L., and Fernandez, E. (1997). Experiments in a Parkinson’s rat model. Science 277, 389-390.doi: 10.1126/science.277. 5324.389
100. Paratcha, G., Ledda, F., and Ibanez, C. F. (2003). The neural cell adhesion molecule NCAM is an alternative signaling receptor for GDNF family ligands. Cell 113, 867-879.doi: 10.1016/s0092-8674(03)00435-5
101. Pardal, R., Ortega-Saenz, P., Duran, R., and Lopez-Barneo, J. (2007). Glia-like stem cells sustain physiologic neurogenesis in the adult mammalian carotid body. Cell 131, 364-377.doi: 10.1016/j.cell.2007.07.043
102. Pascual, A., Hidalgo-Figueroa, M., Gomez-Diaz, R., and Lopez-Barneo, J. (2011). GDNF and protection of adult central catecholaminergic neurons. J. Mol. Endocrinol. 46, R83-R92.doi: 10.1530/jme-10-0125
103. Pascual, A., Hidalgo-Figueroa, M., Piruat, J. I., Pintado, C. O., Gomez-Diaz, R., and Lopez-Barneo, J. (2008). Absolute requirement of GDNF for adult catecholaminergic neuron survival. Nat. Neurosci. 11, 755-761.doi: 10.1038/nn.2136
104. Patel, N. K., Bunnage, M., Plaha, P., Svendsen, C. N., Heywood, P., and Gill, S. S.. Intraputamenal infusion of glial cell line-derived neurotrophic factor in PD: a two-year outcome study. Ann. Neurol. 57, 298-302.doi: 10.1002/ana.20374
105. Pichel, J., Shen, L., Sheng, H. Z., Granholm, A. C., Drago, J., Grinberg, A., et al. Defects in enteric innervation and kidney development in mice lacking GDNF. Nature 382, 73-76.doi: 10.1038/382073a0
106. Platero Luengo A., Gonzalez-Granero S., Duran, R., Diaz-Castro, B., Piruat, J. I., Garcia-Verdugo, J. M., et al. (2014). An O2-sensitive glomus cell-stem cell synapse induces carotid body growth in chronic hypoxia. Cell 156, 291-303.doi: 10.1016/j.cell.2013.12.013
107. Pothos, E. N., Davila, V., and Sulzer, D. (1998). Presynaptic recording of quanta from midbrain dopamine neurons and modulation of the quantal size. J. Neurosci. 18,4106-4118.
108. Proschel, C., Stripay, J. L., Shih, C.-H., Munger, J. C., and Noble, M. D. (2014). Delayed transplantation of precursor cell-derived astrocytes provides multiple benefits in a rat model of Parkinsons. EMBO Mol. Med. 6, 504-518.doi: 10.1002/emmm.201302878
109. Quintino, L., Manfre, G., Wettergren, E. E., Namislo, A., Isaksson, C., and Lundberg, C. (2013). Functional neuroprotection and efficient regulation of GDNF using destabilizing domains in a rodent model of Parkinson’s disease. Mol. Ther.21, 2169-2180.doi: 10.1038/mt.20 13.169
110. Rodriguez-Pallares, J., Joglar, B., Munoz-Manchado, A. B., Villadiego, J., Toledo-Aral, J. J., and Labandeira-Garcia, J. L. (2012). Cografting of carotid body cells improves the long-term survival, fiber outgrowth and functional effects of grafted dopaminergic neurons. Regen. Med. 7, 309-322.doi: 10.2217/rme. 12.22
111. Saavedra, A., Baltazar, G., Carvalho, C. M., and Duarte, E. P. (2005). GDNF modulates HO-1 expression in substantia nigra postnatal cell cultures. Free Radic. Biol. Med. 39, 1611-1619.doi: 10.1016/j.freeradbiomed.2005. 08.005
112. Sanchez, M.P., Silos-Santiago, I., Frisen, J., He, B., Lira, S. A., and Barbacid, M. (1996). Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature382, 70-73.doi: 10.1038/382070a0
113. Sawada, H., Ibi, M., Kihara, T., Urushitani, M., Nakanishi, M., Akaike, A., et al. (2000). Neuroprotective mechanism of glial cell line-derived neurotrophic factor in mesencephalic neurons. J. Neurochem. 74, 1175-1184.doi: 10.1046/j.1471-4159.2000.741175.x
114. Schaar, D. G., Sieber, B. A., Dreyfus, C. F., and Black, I. B. (1993). Regional and cell-specific expression of GDNF in rat brain. Exp. Neurol. 124, 368-371.doi: 10.1006/exnr.1993.1207
115. Shao, Z., Dyck, L. E., Wang, H., and Li, X. M. (2006).Antipsychotic drugs cause glial cell line derived neurotrophic factor secretion from C6 glioma cells. J. Psychiatry Neurosci. 31, 32-37.
116. Slevin, J. T., Gerhardt, G. A., Smith, C. D., Gash, D. M., Kryscio, R., and Young, (2005). Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor. J. Neurosurg. 102, 216-222.doi: 10.3171/jns.2005.102.2.0216
117. Smith, M.P., and Cass, W. A. (2007). GDNF reduces oxidative stress in a 6-hydroxydopamine model of Parkinson’s disease. Neurosci. Lett. 412, 259-263.doi: 10.1016/j.neulet.2006.11.017
118. Smith, M. P., Fletcher-Turner, A., Yurek, D. M., and Cass, W. A. (2006). Calcitriol protection against dopamine loss induced by intracerebroventricular administration of 6-hydroxydopamine. Neurochem. Res. 31, 533-539.doi: 10.1007/s11064-006-9048-4
119. Sredni, B., Geffen-Aricha, R., Duan, W., Albeck, M., Shalit, F., Lander, H. M., et al.. Multifunctional tellurium molecule protects and restores dopaminergic neurons in Parkinson’s disease models. FASEB J.21, 1870-1883.doi: 10.1096/fj.06-7500com
120. Su, T.-P., Wu, X. Z., Cone, E. J., Shukla, K., Gund, T. M., Dodge, A. L., et al. (1991). Sigma compounds derived from phencyclidine: identification of PRE-084, a new, selective sigma ligand. J. Pharmacol. Exp. Ther.259, 543-550.
121. Subramaniam, S.R., and Chesselet, M.-F. (2013). Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog. Neurobiol. 106-107, 17-32.doi: 10.1016/j.pneurobio.2013.04.004
122. Tai, K., Quintino, L., Isaksson, C., Gussing, F., and Lundberg, C. (2012). Destabilizing domains mediate reversible transgene expression in the brain. PLoS One 7:e46269.doi: 10.1371/journal.pone.0046269
123. Tajiri, N., Yasuhara, T., Shingo, T., Kondo, A., Yuan, W., Kadota, T., et al. (2010). Exercise exerts neuroprotective effects on Parkinson’s disease model of rats. Brain Res. 1310, 200-207.doi: 10.1016/j.brainres.2009. 10.075
124. Tang, Y.P., Ma, Y. L., Chao, C. C., Chen, K. Y., and Lee, E. H. Y. (1998). Enhanced glial cell line-derived neurotrophic factor mRNA expression upon (-)-deprenyl and melatonin treatments. J. Neurosci. Res. 53, 593-604.doi: 10.1002/(sici)1097-4547(19980901)53:5<593::aid-jnr9>3.3.co;2-7
125. Tarazi, F. I., Sahli, Z. T., Wolny, M., and Mousa, S. A. (2014). Emerging therapies for Parkinson’s disease: from bench to bedside. Pharmacol. Ther. 144, 123-133.doi: 10.1016/j.pharmthera.2014.05.010
126. Tatarewicz, S. M., Wei, X., Gupta, S., Masterman, D., Swanson, S. J., and Moxness, M. S. (2007). Development of a maturing T-cell-mediated immune response in patients with idiopathic Parkinson’s disease receiving r-metHuGDNF via continuous intraputaminal infusion. J. Clin. Immunol.27, 620-627.doi: 10.1007/s10875-007-9117-8
127. Tereshchenko, J., Maddalena, A., Bahr, M., and Kugler, S. (2014). Pharmacologically controlled, discontinuous GDNF gene therapy restores motor function in a rat model of Parkinson’s disease. Neurobiol. Dis. 65, 35-42.doi: 10.1016/j.nbd.2014.01.009
128. Tomac, A., Lindqvist, E., Lin, L. F., Ogren, S. O., Young, D., Hoffer, B. J., et al. (1995a). Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 373, 335-339.doi: 10.1038/373335a0
129. Tomac, A., Widenfalk, J., Lin, L. F., Kohno, T., Ebendal, T., Hoffer, B. J., et al. (1995b). Retrograde axonal transport of glial cell line-derived neurotrophic factor in the adult nigrostriatal system suggests a trophic role in the adult. Proc. Natl. Acad. Sci. USA 92, 8274-8278.doi: 10.1073/pnas.92.18. 8274
130. Tornqvist, N., Bjorklund, L., Almqvist, P., Wahlberg, L., and Stromberg, I. Implantation of bioactive growth factor-secreting rods enhances fetal dopaminergic graft survival, outgrowth density and functional recovery in a rat model ofParkinson’s disease. Exp. Neurol. 164,130-138.doi: 10.1006/exnr.2000. 7411
131. Trupp, M., Belluardo, N., Funakoshi, H., and Ibanez, C. F. (1997). Complementary and overlapping expression of glial cell line-derived neurotrophic factor (GDNF), c-ret proto-oncogene and GDNF receptor-alpha indicates multiple mechanisms of trophic actions in the adult rat CNS. J. Neurosci. 17, 3554-3567.
132. Tseng, J. L., Baetge, E. E., Zurn, A. D., and Aebischer, P. (1997). GDNF reduces drug-induced rotational behavior after medial forebrain bundle transection by a mechanism not involving striatal dopamine. J. Neurosci. 17, 325-333.
133. Ugarte, S. D., Lin, E., Klann, E., Zigmond, M. J., and Perez, R. G. (2003). Effects of GDNF on 6-OHDA-induced death in a dopaminergic cell line: modulation by inhibitors ofPI3 kinase andMEK. J. Neurosci. Res. 73, 105-112.doi: 10.1002/jnr. 10632
134. Villadiego, J., Mendez-Ferrer, S., Valdes-Sanchez, T., Silos-Santiago, I., Farinas, Lopez-Barneo, J., et al. (2005). Selective glial cell line-derived neurotrophic factor production in adult dopaminergic carotid body cells in situ and after intrastriatal transplantation. J. Neurosci.25, 4091-4098.doi: 10.1523/jneurosci. 4312-04.2005
135. Wang, C. Y., Yang, F., He, X., Chow, A., Du, J., Russell, J. T., et al. (2001). Ca2+ binding protein frequenin mediates GDNF-induced potentiation of Ca2+ channels and transmitter release. Neuron 32, 99-112.doi: 10.1016/s0896-6273(01)00434-2
136. Wartiovaara, K., Hytonen, M., Vuori, M., Paulin, L., Rinne, J., and Sariola, H.. Mutation analysis of the glial cell line-derived neurotrophic factor gene in Parkinson’s disease. Exp. Neurol. 152, 307-309.doi: 10.1006/exnr.1998. 6857
137. Winkler, C., Sauer, H., Lee, C. S., and Bjorklund, A. (1996). Short-term GDNF treatment provides long-term rescue of lesioned nigral dopaminergic neurons in a rat model of Parkinson’s disease. J. Neurosci. 16, 7206-7215.
138. Wu, X., Chen, P. S., Dallas, S., Wilson, B., Block, M. L., Wang, C.-C., et al. (2008). Histone deacetylase inhibitors up-regulate astrocyte GDNF and BDNF gene transcription and protect dopaminergic neurons. Int. J. Neuropsychopharmacol. 1123-1134.doi: 10.1017/s1461145708009024
139. Xia, C.-F., Boado, R. J., Zhang, Y., Chu, C., and Pardridge, W. M. (2008). Intravenous glial-derived neurotrophic factor gene therapy of experimental Parkinson’s disease with Trojan horse liposomes and a tyrosine hydroxylase promoter. J. Gene Med. 10, 306-315.doi: 10.1002/jgm.1152
140. Xu, K., and Dluzen, D. E. (2000). The effect of GDNF on nigrostriatal dopaminergic function in response to atwo-pulseK(+) stimulation. Exp. Neurol. 166,450-457.doi: 10.1006/exnr.2000.7515
141. Yamagata, K., Tagami, M., Ikeda, K., Tsumagari, S., Yamori, Y., and Nara, Y. (2002). Differential regulation of glial cell line-derived neurotrophic factor (GDNF) mRNA expression during hypoxia and reoxygenation in astrocytes isolated from stroke-prone spontaneously hypertensive rats. Glia 37, 1-7.doi: 10.1002/glia. 10003
142. Yan, Q., Matheson, C., and Lopez, O. T. (1995). In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neurons. Nature 373, 341-344.doi: 10.1038/373341a0
143. Yurek, D. M., Flectcher, A. M., Kowalczyk, T. H., Padegimas, L., and Cooper, M. J. (2009). Compacted DNA nanoparticle gene transfer of GDNF to the rat striatum enhances the survival of grafted fetal dopamine neurons. Cell Transplant. 18, 1183-1196.doi: 10.3727/096368909x12483162196881
144. Zhang, Y., and Pardridge, W. M. (2009). Near complete rescue of experimental Parkinson’s disease with intravenous, non-viral GDNF gene therapy. Pharm. Res. 1059-1063.doi: 10.1007/s11095-008-9815-9
145. Zhao, Q., Gao, J., Li, W., and Cai, D. (2010). Neurotrophic and neurorescue effects of Echinacoside in the subacute MPTP mouse model of Parkinson’s disease. BrainRes. 1346,224-236.doi: 10.1016/j.brainres.2010.05.018
146. Zhu, G., Wang, X., Chen, Y., Yang, S., Cheng, H., Wang, N., et al. (2010). Puerarin protects dopaminergic neurons against 6-hydroxydopamine neurotoxicity via inhibiting apoptosis and upregulating glial cell line-derived neurotrophic factor in a rat model ofParkinson’s disease. Planta Med. 76,1820-1826.doi: 10.1055/s-0030-1249976
147. Zhu, G., Wang, X., Wu, S., Li, X., and Li, Q. (2014). Neuroprotective effects of puerarin on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced Parkinson’s disease model in mice. Phytother. Res.28, 179-186.doi: 10.1002/ptr.4975
148. Zigmond, M. J., Cameron, J. L., Leak, R. K., Mirnics, K., Russell, V. A., Smeyne, R. J., et al. (2009). Triggering endogenous neuroprotective processes through exercise in models of dopamine deficiency. ParkinsonismRelat. Disord. 15(Suppl. 3), S42-S45.doi: 10.1016/s1353-8020(09)70778-3