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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Neuroregeneration in Parkinson’s Disease: From Proteins to Small Molecules

Author(s): Yulia A. Sidorova*, Konstantin P. Volcho* and Nariman F. Salakhutdinov

Volume 17, Issue 3, 2019

Page: [268 - 287] Pages: 20

DOI: 10.2174/1570159X16666180905094123

Price: $65

Abstract

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide, the lifetime risk of developing this disease is 1.5%. Motor diagnostic symptoms of PD are caused by degeneration of nigrostriatal dopamine neurons. There is no cure for PD and current therapy is limited to supportive care that partially alleviates disease signs and symptoms. As diagnostic symptoms of PD result from progressive degeneration of dopamine neurons, drugs restoring these neurons may significantly improve treatment of PD.

Method: A literature search was performed using the PubMed, Web of Science and Scopus databases to discuss the progress achieved in the development of neuroregenerative agents for PD. Papers published before early 2018 were taken into account.

Results: Here, we review several groups of potential agents capable of protecting and restoring dopamine neurons in cultures or animal models of PD including neurotrophic factors and small molecular weight compounds.

Conclusion: Despite the promising results of in vitro and in vivo experiments, none of the found agents have yet shown conclusive neurorestorative properties in PD patients. Meanwhile, a few promising biologicals and small molecules have been identified. Their further clinical development can eventually give rise to disease-modifying drugs for PD. Thus, intensive research in the field is justified.

Keywords: Neurorestoration, neuroprotection, Parkinson's disease, neurotrophic factors, GDNF, dopamine neurons, RET agonists, Trk agonists, BDNF, GDNF mimetics, BDNF mimetics.

Graphical Abstract

[1]
Nasrolahi A, Mahmoudi J, Akbarzadeh A, et al. Neurotrophic Factors Hold Promise for the Future of Parkinson’s Disease Treatment: Is There a Light at the End of the Tunnel? Rev Neurosci 2018; 29(5): 475-90.
[PMID: [https://doi.org/10.1515/revneuro-2017-0040]
[2]
Cheng HC, Ulane CM, Burke RE. Clinical progression in Parkinson disease and the neurobiology of axons. Ann Neurol 2010; 67(6): 715-25.
[http://dx.doi.org/10.1002/ana.21995] [PMID: 20517933]
[3]
Blesa J, Przedborski S. Parkinson’s disease: animal models and dopaminergic cell vulnerability. Front Neuroanat 2014; 8: 155.
[http://dx.doi.org/10.3389/fnana.2014.00155] [PMID: 25565980]
[4]
Dawson TM, Ko HS, Dawson VL. Genetic animal models of Parkinson’s disease. Neuron 2010; 66(5): 646-61.
[http://dx.doi.org/dx. doi.org/10.1016/j.neuron.2010.04.034] [PMID: 20547124]
[5]
Ramonet D, Daher JPL, Lin BM, et al. Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2. PLoS One 2011; 6(4): e18568.
[http://dx.doi.org/10.1371/journal.pone.0018568] [PMID: 21494637]
[6]
Chen CY, Weng YH, Chien KY, et al. (G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD. Cell Death Differ 2012; 19(10): 1623-33.
[http://dx.doi.org/10.1038/cdd.2012.42] [PMID: 22539006]
[7]
Stolp HB. Neuropoietic cytokines in normal brain development and neurodevelopmental disorders. Mol Cell Neurosci 2013; 53: 63-8.
[http://dx.doi.org/10.1016/j.mcn.2012.08.009] [PMID: 22926235]
[8]
Nathanson NM. Regulation of neurokine receptor signaling and trafficking. Neurochem Int 2012; 61(6): 874-8.
[http://dx.doi.org/dx.doi. org/10.1016/j.neuint.2012.01.018] [PMID: 22306348]
[9]
Bauer S, Kerr BJ, Patterson PH. The neuropoietic cytokine family in development, plasticity, disease and injury. Nat Rev Neurosci 2007; 8(3): 221-32.
[http://dx.doi.org/10.1038/nrn2054] [PMID: 17311007]
[10]
Razavi S, Nazem G, Mardani M, Esfandiari E, Salehi H, Esfahani SHZ. Neurotrophic factors and their effects in the treatment of multiple sclerosis. Adv Biomed Res 2015; 4: 53.
[http://dx.doi.org/10.4103/2277-9175.151570] [PMID: 25802822]
[11]
Loy B, Apostolova G, Dorn R, McGuire V. a; Arthur, J. S. C.; Dechant, G. P38A and P38B Mitogen-Activated Protein Kinases Determine Cholinergic Transdifferentiation of Sympathetic Neurons. J Neurosci 2011; 31(34): 12059-67.
[http://dx.doi.org/ 10.1523/JNEUROSCI.0448-11.2011] [PMID: 21865449]
[12]
Bauer S. Cytokine control of adult neural stem cells. Ann N Y Acad Sci 2009; 1153(1): 48-56.
[http://dx.doi.org/10.1111/j.1749-6632.2009.03986.x] [PMID: 19236327]
[13]
Yang P, Arnold SA, Habas A, Hetman M, Hagg T. Ciliary neurotrophic factor mediates dopamine D2 receptor-induced CNS neurogenesis in adult mice. J Neurosci 2008; 28(9): 2231-41.
[http://dx.doi.org/10.1523/JNEUROSCI.3574-07.2008] [PMID: 18305256]
[14]
Nam JH, Park ES, Won SY, et al. TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson’s disease via CNTF. Brain 2015; 138(Pt 12): 3610-22.
[http://dx.doi.org/10.1093/brain/awv297] [PMID: 26490328]
[15]
Hagg T, Varon S. Ciliary neurotrophic factor prevents degeneration of adult rat substantia nigra dopaminergic neurons in vivo. Proc Natl Acad Sci USA 1993; 90(13): 6315-9.
[http://dx.doi.org/dx. doi.org/10.1073/pnas.90.13.6315] [PMID: 8101002]
[16]
Ling ZD, Potter ED, Lipton JW, Carvey PM. Differentiation of mesencephalic progenitor cells into dopaminergic neurons by cytokines. Exp Neurol 1998; 149(2): 411-23.
[http://dx.doi.org/ 10.1006/exnr.1998.6715] [PMID: 9500954]
[17]
Zhao J-W, Dyson SC, Kriegel C, et al. Modelling of a targeted nanotherapeutic ‘stroma’ to deliver the cytokine LIF, or XAV939, a potent inhibitor of Wnt-β-catenin signalling, for use in human fetal dopaminergic grafts in Parkinson’s disease. Dis Model Mech 2014; 7(10): 1193-203.
[http://dx.doi.org/10.1242/dmm.015859] [PMID: 25085990]
[18]
Kim T-S, Misumi S, Jung C-G, et al. Increase in dopaminergic neurons from mouse embryonic stem cell-derived neural progenitor/stem cells is mediated by hypoxia inducible factor-1alpha. J Neurosci Res 2008; 86(11): 2353-62.
[http://dx.doi.org/10.1002/jnr.21687] [PMID: 18438929]
[19]
Storch A, Paul G, Csete M, et al. Long-term proliferation and dopaminergic differentiation of human mesencephalic neural precursor cells. Exp Neurol 2001; 170(2): 317-25.
[http://dx.doi.org/10.1006/exnr. 2001.7706] [PMID: 11476598]
[20]
Howells DW, Wong JY, Churchyard AJ, Donnan GA. Leukaemia inhibitory factor prevents injury induced proliferation of striatal dopamine uptake sites. Neuroreport 1995; 6(14): 1857-60.
[http://dx.doi.org/10.1097/00001756-199510020-00009] [PMID: 8547584]
[21]
Liu J, Zang D. Response of neural precursor cells in the brain of Parkinson’s disease mouse model after LIF administration. Neurol Res 2009; 31(7): 681-6.
[http://dx.doi.org/10.1179/174313209X382368] [PMID: 19108756]
[22]
Liu Y, Peng M, Zang D, Zhang B. Leukemia inhibitory factor promotes nestin-positive cells, and increases gp130 levels in the Parkinson disease mouse model of 6-hydroxydopamine. Neurosciences (Riyadh) 2013; 18(4): 363-70.
[PMID: 24141460]
[23]
A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. Neurology 1996; 46(5): 1244-9.
[http://dx.doi.org/10.1212/WNL.46.5.1244] [PMID: 8628460]
[24]
Sieving PA, Caruso RC, Tao W, et al. Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants. Proc Natl Acad Sci USA 2006; 103(10): 3896-901.
[http://dx.doi.org/10.1073/pnas.0600236103] [PMID: 16505355]
[25]
Cohen S, Levi-Montalcini R, Hamburger V. A nerve growth-stimulating factor isolated from sarcom as 37 and 180. Proc Natl Acad Sci USA 1954; 40(10): 1014-8.
[http://dx.doi.org/10. 1073/pnas.40.10.1014] [PMID: 16589582]
[26]
Levi-Montalcini R, Cohen S. In Vitro and in Vivo Effects of a Nerve Growth-Stimulating Agent Isolated from Snake Venom. Proc Natl Acad Sci USA 1956; 42(9): 695-9.
[http://dx.doi.org/dx.doi. org/10.1073/pnas.42.9.695] [PMID: 16589933]
[27]
Sánchez-Sánchez J, Arévalo JC. A Review on Ubiquitination of Neurotrophin Receptors: Facts and Perspectives. Int J Mol Sci 2017; 18(3): 630.
[http://dx.doi.org/10.3390/ijms18030630] [PMID: 28335430]
[28]
Esposito D, Patel P, Stephens RM, et al. The cytoplasmic and transmembrane domains of the p75 and Trk A receptors regulate high affinity binding to nerve growth factor. J Biol Chem 2001; 276(35): 32687-95.
[http://dx.doi.org/10.1074/jbc.M011674200] [PMID: 11435417]
[29]
Lad SP, Peterson DA, Bradshaw RA, Neet KE. Individual and combined effects of TrkA and p75NTR nerve growth factor receptors. A role for the high affinity receptor site. J Biol Chem 2003; 278(27): 24808-17.
[http://dx.doi.org/10.1074/jbc.M212270200] [PMID: 12702729]
[30]
Ceni C, Kommaddi RP, Thomas R, et al. The p75NTR intracellular domain generated by neurotrophin-induced receptor cleavage potentiates Trk signaling. J Cell Sci 2010; 123(Pt 13): 2299-307.
[http://dx.doi.org/10.1242/jcs.062612] [PMID: 20530577]
[31]
Meldolesi J. Neurotrophin receptors in the pathogenesis, diagnosis and therapy of neurodegenerative diseases. Pharmacol Res 2017; 121: 129-37.
[http://dx.doi.org/10.1016/j.phrs.2017.04.024] [PMID: 28438600]
[32]
Nykjaer A, Willnow TE, Petersen CM. p75NTR--live or let die. Curr Opin Neurobiol 2005; 15(1): 49-57.
[http://dx.doi.org/ 10.1016/j.conb.2005.01.004] [PMID: 15721744]
[33]
Lorigados Pedre L, Pavón Fuentes N, Alvarez González L, et al. Nerve growth factor levels in Parkinson disease and experimental parkinsonian rats. Brain Res 2002; 952(1): 122-7.
[http://dx.doi.org/10.1016/S0006-8993(02)03222-5] [PMID: 12363411]
[34]
Lorigados L, Alvarez P, Pavón N, Serrano T, Blanco L, Macías R. NGF in experimental models of Parkinson disease. Mol Chem Neuropathol 1996; 28(1-3): 225-8.
[http://dx.doi.org/ 10.1007/BF02815226] [PMID: 8871963]
[35]
Mogi M, Togari A, Kondo T, et al. Brain-derived growth factor and nerve growth factor concentrations are decreased in the substantia nigra in Parkinson’s disease. Neurosci Lett 1999; 270(1): 45-8.
[http://dx.doi.org/ dx.doi.org/10.1016/S0304-3940(99)00463-2] [PMID: 10454142]
[36]
Huang Y, Yun W, Zhang M, Luo W, Zhou X. Serum concentration and clinical significance of brain-derived neurotrophic factor in patients with Parkinson’s disease or essential tremor. J Int Med Res 2018; 46(4): 1477-85.
[http://dx.doi.org/10.1177/0300060517748843] [PMID: 29350074]
[37]
Wang YQ, Bian GL, Bai Y, Cao R, Chen LW. Identification and kainic acid-induced up-regulation of low-affinity p75 neurotrophin receptor (p75NTR) in the nigral dopamine neurons of adult rats. Neurochem Int 2008; 53(3-4): 56-62.
[http://dx.doi.org/ 10.1016/j.neuint.2008.06.007] [PMID: 18639597]
[38]
Numan S, Seroogy KB. Expression of trkB and trkC mRNAs by adult midbrain dopamine neurons: a double-label in situ hybridization study. J Comp Neurol 1999; 403(3): 295-308.
[http://dx.doi.org/dx.doi. org/10.1002/(SICI)1096-9861(19990118)403:3<295:AID-CNE2> 3.0.CO;2-L] [PMID: 9886032]
[39]
Melchior B, Nerrière-Daguin V, Laplaud DA, et al. Ectopic expression of the TrkA receptor in adult dopaminergic mesencephalic neurons promotes retrograde axonal NGF transport and NGF-dependent neuroprotection. Exp Neurol 2003; 183(2): 367-78.
[http://dx.doi.org/10.1016/S0014-4886(03)00137-7] [PMID: 14552878]
[40]
Hyman C, Hofer M, Barde YA, et al. BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 1991; 350(6315): 230-2.
[http://dx.doi.org/10.1038/350230a0] [PMID: 2005978]
[41]
Hyman C, Juhasz M, Jackson C, Wright P, Ip NY, Lindsay RM. Overlapping and distinct actions of the neurotrophins BDNF, NT-3, and NT-4/5 on cultured dopaminergic and GABAergic neurons of the ventral mesencephalon. J Neurosci 1994; 14(1): 335-47.
[http://dx.doi.org/10.1523/JNEUROSCI.14-01-00335.1994] [PMID: 8283241]
[42]
Studer L, Spenger C, Seiler RW, Altar CA, Lindsay RM, Hyman C. Comparison of the effects of the neurotrophins on the morphological structure of dopaminergic neurons in cultures of rat substantia nigra. Eur J Neurosci 1995; 7(2): 223-33.
[http://dx.doi.org/dx. doi.org/10.1111/j.1460-9568.1995.tb01058.x] [PMID: 7757259]
[43]
Blöchl A, Sirrenberg C. Neurotrophins stimulate the release of dopamine from rat mesencephalic neurons via Trk and p75Lntr receptors. J Biol Chem 1996; 271(35): 21100-7.
[http://dx.doi.org/dx.doi. org/10.1074/jbc.271.35.21100] [PMID: 8702878]
[44]
Chaturvedi RK, Shukla S, Seth K, Agrawal AK. Nerve growth factor increases survival of dopaminergic graft, rescue nigral dopaminergic neurons and restores functional deficits in rat model of Parkinson’s disease. Neurosci Lett 2006; 398(1-2): 44-9.
[http://dx.doi.org/10.1016/j.neulet.2005.12.042] [PMID: 16423459]
[45]
Hagg T. Neurotrophins prevent death and differentially affect tyrosine hydroxylase of adult rat nigrostriatal neurons in vivo. Exp Neurol 1998; 149(1): 183-92.
[http://dx.doi.org/10.1006/exnr. 1997.6684] [PMID: 9454627]
[46]
Fusco D, Vargiolu M, Vidone M, et al. The RET51/FKBP52 complex and its involvement in Parkinson disease. Hum Mol Genet 2010; 19(14): 2804-16.
[http://dx.doi.org/10.1093/hmg/ddq181] [PMID: 20442138]
[47]
Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 1993; 260(5111): 1130-2.
[http://dx.doi.org/dx. doi.org/10.1126/science.8493557] [PMID: 8493557]
[48]
Olson L, Backlund EO, Ebendal T, et al. Intraputaminal infusion of nerve growth factor to support adrenal medullary autografts in Parkinson’s disease. One-year follow-up of first clinical trial. Arch Neurol 1991; 48(4): 373-81.
[http://dx.doi.org/10.1001/archneur.1991.00530160037011] [PMID: 2012510]
[49]
Sydow O, Hansson P, Young D, et al. Long-term beneficial effects of adrenal medullary autografts supported by nerve growth factor in Parkinson’s disease. Eur J Neurol 1995; 2(5): 445-54.
[http://dx.doi.org/10.1111/j.1468-1331.1995.tb00154.x] [PMID: 24283725]
[50]
Spina MB, Squinto SP, Miller J, Lindsay RM, Hyman C. Brain-derived neurotrophic factor protects dopamine neurons against 6-hydroxydopamine and N-methyl-4-phenylpyridinium ion toxicity: involvement of the glutathione system. J Neurochem 1992; 59(1): 99-106.
[http://dx.doi.org/10.1111/j.1471-4159.1992. tb08880.x] [PMID: 1613515]
[51]
Altar CA, Boylan CB, Fritsche M, et al. Efficacy of brain-derived neurotrophic factor and neurotrophin-3 on neurochemical and behavioral deficits associated with partial nigrostriatal dopamine lesions. J Neurochem 1994; 63(3): 1021-32.
[http://dx.doi.org/ 10.1046/j.1471-4159.1994.63031021.x] [PMID: 7519657]
[52]
Zhang S, Chen S, Liu A, et al. Inhibition of BDNF Production by MPP+ through Up-Regulation of MiR-210-3p Contributes to Dopaminergic Neuron Damage in MPTP Model. Neurosci Lett 2018; 675: 133-9.
[http://dx.doi.org/[https://doi.org/10.1016/j.neulet.2017.10.014]
[53]
Kang SS, Zhang Z, Liu X, et al. TrkB neurotrophic activities are blocked by α-synuclein, triggering dopaminergic cell death in Parkinson’s disease. Proc Natl Acad Sci USA 2017; 114(40): 10773-8.
[http://dx.doi.org/10.1073/pnas.1713969114] [PMID: 28923922]
[54]
Goes ATR, Jesse CR, Antunes MS, et al. Protective role of chrysin on 6-hydroxydopamine-induced neurodegeneration a mouse model of Parkinson’s disease: Involvement of neuroinflammation and neurotrophins. Chem Biol Interact 2018; 279: 111-20.
[http://dx.doi.org/10.1016/j.cbi.2017.10.019] [PMID: 29054324]
[55]
Siracusa R, Paterniti I, Cordaro M, et al. Neuroprotective Effects of Temsirolimus in Animal Models of Parkinson’s Disease. Mol Neurobiol 2018; 55(3): 2403-19.
[http://dx.doi.org/[https://doi.org/10.1007/s12035-017-0496-4] [PMID: 28357809]
[56]
Kaur B, Prakash A. Ceftriaxone attenuates glutamate-mediated neuro-inflammation and restores BDNF in MPTP model of Parkinson’s disease in rats. Pathophysiology 2017; 24(2): 71-9.
[http://dx.doi.org/ dx.doi.org/10.1016/j.pathophys.2017.02.001] [PMID: 28245954]
[57]
Sampaio TB, Pinton S, da Rocha JT, Gai BM, Nogueira CW. Involvement of BDNF/TrkB signaling in the effect of diphenyl diselenide on motor function in a Parkinson’s disease rat model. Eur J Pharmacol 2017; 795(795): 28-35.
[http://dx.doi.org/dx.doi. org/10.1016/j.ejphar.2016.11.054] [PMID: 27915043]
[58]
Shi X, Chen YH, Liu H, Qu HD. Therapeutic effects of paeonol on methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid-induced Parkinson’s disease in mice. Mol Med Rep 2016; 14(3): 2397-404.
[http://dx.doi.org/10.3892/mmr.2016.5573] [PMID: 27484986]
[59]
Zhou W, Barkow JC, Freed CR. Running wheel exercise reduces α-synuclein aggregation and improves motor and cognitive function in a transgenic mouse model of Parkinson’s disease. PLoS One 2017; 12(12): e0190160.
[http://dx.doi.org/10.1371/journal. pone.0190160] [PMID: 29272304]
[60]
da Costa RO, Gadelha-Filho CVJ, da Costa AEM, et al. The Treadmill Exercise Protects against Dopaminergic Neuron Loss and Brain Oxidative Stress in Parkinsonian Rats. Oxid Med Cell Longev 2017; 2017: 2138169.
[http://dx.doi.org/10.1155/2017/2138169] [PMID: 28713483]
[61]
Fischer DL, Kemp CJ, Cole-Strauss A, et al. Subthalamic Nucleus Deep Brain Stimulation Employs trkB Signaling for Neuroprotection and Functional Restoration. J Neurosci 2017; 37(28): 6786-96.
[http://dx.doi.org/dx.doi. org/10.1523/JNEUROSCI.2060-16.2017] [PMID: 28607168]
[62]
Wang Y, Liu H, Du X-D, et al. Association of low serum BDNF with depression in patients with Parkinson’s disease. Parkinsonism Relat Disord 2017; 41(0): 73-8.
[http://dx.doi.org/10.1016/j. parkreldis.2017.05.012] [PMID: 28576603]
[63]
Cagni FC, Campêlo CL. Association of BDNF Val66MET Polymorphism With Parkinson’s Disease and Depression and Anxiety Symptoms. J Neuropsychiatry Clin Neurosci 2017; 29(2): 142-7.
[http://dx.doi.org/[https://doi.org/10.1176/appi.neuropsych.16040062]
[64]
Caspell-Garcia C, Simuni T, Tosun-Turgut D, et al. Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease. PLoS One 2017; 12(5): e0175674.
[http://dx.doi.org/10.1371/journal.pone.0175674] [PMID: 28520803]
[65]
Wang Y, Liu H, Zhang B-S, Soares JC, Zhang XY. Low BDNF is associated with cognitive impairments in patients with Parkinson’s disease. Parkinsonism Relat Disord 2016; 29: 66-71.
[http://dx.doi.org/10.1016/j.parkreldis.2016.05.023] [PMID: 27245919]
[66]
Khalil H, Alomari MA, Khabour OF, Al-Hieshan A, Bajwa JA. Relationship of circulatory BDNF with cognitive deficits in people with Parkinson’s disease. J Neurol Sci 2016; 362: 217-20.
[http://dx.doi.org/10.1016/j.jns.2016.01.032] [PMID: 26944151]
[67]
Kramer E R, Aron L, Ramakers G M J, et al. Absence of Ret Signaling in Mice Causes Progressive and Late Degeneration of the Nigrostriatal System 2007.
[68]
Baquet ZC, Bickford PC, Jones KR. Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta. J Neurosci 2005; 25(26): 6251-9.
[http://dx.doi.org/10.1523/JNEUROSCI.4601-04.2005] [PMID: 15987955]
[69]
Tronci E, Napolitano F, Muñoz A, et al. BDNF over-expression induces striatal serotonin fiber sprouting and increases the susceptibility to l-DOPA-induced dyskinesia in 6-OHDA-lesioned rats. Exp Neurol 2017; 297: 73-81.
[http://dx.doi.org/10.1016/j. expneurol.2017.07.017] [PMID: 28757258]
[70]
Hynes MA, Poulsen K, Armanini M, Berkemeier L, Phillips H, Rosenthal A. Neurotrophin-4/5 is a survival factor for embryonic midbrain dopaminergic neurons in enriched cultures. J Neurosci Res 1994; 37(1): 144-54.
[http://dx.doi.org/10.1002/jnr. 490370118] [PMID: 7908342]
[71]
Urbanics R. NT-3. Takeda/Regeneron/Amgen. IDrugs 2001; 4(7): 820-4.
[PMID: 15995939]
[72]
Sidorova YA, Mätlik K, Paveliev M, et al. Persephin signaling through GFRalpha1: the potential for the treatment of Parkinson’s disease. Mol Cell Neurosci 2010; 44(3): 223-32.
[http://dx.doi.org/10.1016/j.mcn.2010.03.009] [PMID: 20350599]
[73]
Carmillo P, Dagø L, Day ES, et al. Glial cell line-derived neurotrophic factor (GDNF) receptor alpha-1 (GFR alpha 1) is highly selective for GDNF versus artemin. Biochemistry 2005; 44(7): 2545-54.
[http://dx.doi.org/10.1021/bi049247p] [PMID: 15709767]
[74]
Baloh RH, Tansey MG, Golden JP, et al. TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret. Neuron 1997; 18(5): 793-802.
[http://dx.doi.org/10.1016/S0896-6273(00)80318-9] [PMID: 9182803]
[75]
Jing S, Yu Y, Fang M, et al. GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family. J Biol Chem 1997; 272(52): 33111-7.
[http://dx.doi.org/10.1074/jbc.272.52.33111] [PMID: 9407096]
[76]
Wang LC, Shih A, Hongo J, Devaux B, Hynes M. Broad specificity of GDNF family receptors GFRalpha1 and GFRalpha2 for GDNF and NTN in neurons and transfected cells. J Neurosci Res 2000; 61(1): 1-9.
[http://dx.doi.org/10.1002/1097-4547(20000701) 61:1<1:AID-JNR1>3.0.CO;2-J] [PMID: 10861794]
[77]
Airaksinen MS, Saarma M. The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci 2002; 3(5): 383-94.
[http://dx.doi.org/10.1038/nrn812] [PMID: 11988777]
[78]
Paratcha G, Ledda F, Ibáñez CF. The neural cell adhesion molecule NCAM is an alternative signaling receptor for GDNF family ligands. Cell 2003; 113(7): 867-79.
[http://dx.doi.org/10. 1016/S0092-8674(03)00435-5] [PMID: 12837245]
[79]
Bespalov MM, Sidorova YA, Tumova S, et al. Heparan sulfate proteoglycan syndecan-3 is a novel receptor for GDNF, neurturin, and artemin. J Cell Biol 2011; 192(1): 153-69.
[http://dx.doi.org/10.1083/jcb.201009136] [PMID: 21200028]
[80]
Mullican SE, Lin-Schmidt X, Chin CN, et al. GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates. Nat Med 2017; 23(10): 1150-7.
[http://dx.doi.org/10. 1038/nm.4392] [PMID: 28846097]
[81]
Yang L, Chang CC, Sun Z, et al. GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand. Nat Med 2017; 23(10): 1158-66.
[http://dx.doi.org/ 10.1038/nm.4394] [PMID: 28846099]
[82]
Baloh RH, Tansey MG, Lampe PA, et al. Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex. Neuron 1998; 21(6): 1291-302.
[http://dx.doi.org/10.1016/S0896-6273(00)80649-2] [PMID: 9883723]
[83]
Milbrandt J, de Sauvage FJ, Fahrner TJ, et al. Jr Persephin, a novel neurotrophic factor related to GDNF and neurturin. Neuron 1998; 20(2): 245-53.
[http://dx.doi.org/10.1016/S0896-6273(00)80453-5] [PMID: 9491986]
[84]
Horger BA, Nishimura MC, Armanini MP, et al. Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons. J Neurosci 1998; 18(13): 4929-37.
[http://dx.doi.org/10.1523/JNEUROSCI.18-13-04929.1998] [PMID: 9634558]
[85]
Akerud P, Holm PC, Castelo-Branco G, Sousa K, Rodriguez FJ, Arenas E. Persephin-overexpressing neural stem cells regulate the function of nigral dopaminergic neurons and prevent their degeneration in a model of Parkinson’s disease. Mol Cell Neurosci 2002; 21(2): 205-22.
[http://dx.doi.org/10.1006/mcne.2002. 1171] [PMID: 12401443]
[86]
Strelau J, Sullivan A, Böttner M, et al. Growth/differentiation factor-15/macrophage inhibitory cytokine-1 is a novel trophic factor for midbrain dopaminergic neurons in vivo. J Neurosci 2000; 20(23): 8597-603.
[http://dx.doi.org/dx. doi.org/10.1523/JNEUROSCI.20-23-08597.2000] [PMID: 11102463]
[87]
Lindahl M, Poteryaev D, Yu L, et al. Human glial cell line-derived neurotrophic factor receptor alpha 4 is the receptor for persephin and is predominantly expressed in normal and malignant thyroid medullary cells. J Biol Chem 2001; 276(12): 9344-51.
[http://dx.doi.org/10.1074/jbc. M008279200] [PMID: 11116144]
[88]
Kearns CM, Cass WA, Smoot K, Kryscio R, Gash DM. GDNF protection against 6-OHDA: time dependence and requirement for protein synthesis. J Neurosci 1997; 17(18): 7111-8.
[http://dx.doi.org/10.1523/JNEUROSCI.17-18-07111.1997] [PMID: 9278545]
[89]
Kearns CM, Gash DM. GDNF protects nigral dopamine neurons against 6-hydroxydopamine in vivo. Brain Res 1995; 672(1-2): 104-11.
[http://dx.doi.org/10.1016/0006-8993(94)01366-P] [PMID: 7749731]
[90]
Gash DM, Zhang Z, Ovadia A, et al. Functional recovery in parkinsonian monkeys treated with GDNF. Nature 1996; 380(6571): 252-5.
[http://dx.doi.org/dx. doi.org/10.1038/380252a0] [PMID: 8637574]
[91]
Oiwa Y, Yoshimura R, Nakai K, Itakura T. Dopaminergic neuroprotection and regeneration by neurturin assessed by using behavioral, biochemical and histochemical measurements in a model of progressive Parkinson’s disease. Brain Res 2002; 947(2): 271-83.
[http://dx.doi.org/10.1016/S0006-8993(02)02934-7] [PMID: 12176170]
[92]
Kordower JH, Herzog CD, Dass B, et al. Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys. Ann Neurol 2006; 60(6): 706-15.
[http://dx.doi.org/ 10.1002/ana.21032] [PMID: 17192932]
[93]
Hoffer BJ, Hoffman A, Bowenkamp K, et al. Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo. Neurosci Lett 1994; 182(1): 107-11.
[http://dx.doi.org/10.1016/0304-3940(94)90218-6] [PMID: 7891873]
[94]
Yin X, Xu H, Jiang Y, et al. The effect of lentivirus-mediated PSPN genetic engineering bone marrow mesenchymal stem cells on Parkinson’s disease rat model. PLoS One 2014; 9(8): e105118.
[http://dx.doi.org/10.1371/journal.pone.0105118] [PMID: 25118697]
[95]
Nutt JG, Burchiel KJ, Comella CL, et al. Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology 2003; 60(1): 69-73.
[http://dx.doi.org/10.1212/WNL.60.1.69] [PMID: 12525720]
[96]
Gill SS, Patel NK, Hotton GR, et al. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med 2003; 9(5): 589-95.
[http://dx.doi.org/10. 1038/nm850] [PMID: 12669033]
[97]
Slevin JT, Gerhardt GA, Smith CD, Gash DM, Kryscio R, Young B. Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor. J Neurosurg 2005; 102(2): 216-22.
[http://dx.doi.org/10.3171/jns.2005.102.2. 0216] [PMID: 15739547]
[98]
Lang AE, Gill S, Patel NK, et al. Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease. Ann Neurol 2006; 59(3): 459-66.
[http://dx.doi.org/10.1002/ana.20737] [PMID: 16429411]
[99]
Penn RD, Dalvi A, Slevin J, et al. GDNF in treatment of Parkinson’s disease: response to editorial. Lancet Neurol 2006; 5(3): 202-3.
[http://dx.doi.org/dx. doi.org/10.1016/S1474-4422(06)70360-X] [PMID: 16488374]
[100]
Piltonen M, Bespalov MM, Ervasti D, et al. Heparin-binding determinants of GDNF reduce its tissue distribution but are beneficial for the protection of nigral dopaminergic neurons. Exp Neurol 2009; 219(2): 499-506.
[http://dx.doi.org/10.1016/j. expneurol.2009.07.002] [PMID: 19615368]
[101]
Salvatore MF, Ai Y, Fischer B, et al. Point source concentration of GDNF may explain failure of phase II clinical trial. Exp Neurol 2006; 202(2): 497-505.
[http://dx.doi.org/10.1016/j.expneurol. 2006.07.015] [PMID: 16962582]
[102]
Hutchinson M, Gurney S, Newson R. GDNF in Parkinson disease: an object lesson in the tyranny of type II. J Neurosci Methods 2007; 163(2): 190-2.
[http://dx.doi.org/10.1016/j.jneumeth. 2006.06.015] [PMID: 16876872]
[103]
Matcham J, McDermott MP, Lang AE. GDNF in Parkinson’s disease: the perils of post-hoc power. J Neurosci Methods 2007; 163(2): 193-6.
[http://dx.doi.org/10.1016/j.jneumeth.2007.05.003] [PMID: 17540454]
[106]
Marks WJ Jr, Ostrem JL, Verhagen L, et al. Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic Parkinson’s disease: an open-label, phase I trial. Lancet Neurol 2008; 7(5): 400-8.
[http://dx.doi.org/ dx.doi.org/10.1016/S1474-4422(08)70065-6] [PMID: 18387850]
[107]
Marks WJ Jr, Bartus RT, Siffert J, et al. Gene delivery of AAV2-neurturin for Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol 2010; 9(12): 1164-72.
[http://dx.doi.org/10.1016/S1474-4422(10)70254-4] [PMID: 20970382]
[108]
Bartus RT, Herzog CD, Chu Y, et al. Bioactivity of AAV2-neurturin gene therapy (CERE-120): differences between Parkinson’s disease and nonhuman primate brains. Mov Disord 2011; 26(1): 27-36.
[http://dx.doi.org/10. 1002/mds.23442] [PMID: 21322017]
[109]
Bartus RT, Baumann TL, Siffert J, et al. Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients. Neurology 2013; 80(18): 1698-701.
[http://dx.doi.org/10.1212/WNL.0b013e3182904faa] [PMID: 23576625]
[110]
Warren Olanow C, Bartus RT, Baumann TL, et al. Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double-blind, randomized, controlled trial. Ann Neurol 2015; 78(2): 248-57.
[http://dx.doi.org/10.1002/ana.24436] [PMID: 26061140]
[111]
Bartus RT, Johnson EM Jr. 2017.
[112]
Luz M, Mohr E, Fibiger HC. GDNF-induced cerebellar toxicity: A brief review. Neurotoxicology 2016; 52: 46-56.
[http://dx.doi.org/dx. doi.org/10.1016/j.neuro.2015.10.011] [PMID: 26535469]
[113]
Lang AE, Langston JW, Stoessl AJ, et al. GDNF in treatment of Parkinson’s disease: response to editorial. Lancet Neurol 2006; 5(3): 200-2.
[http://dx.doi.org/10.1016/S1474-4422(06)70359-3] [PMID: 16488373]
[114]
Runeberg-Roos P, Piccinini E, Penttinen A-M, et al. Developing therapeutically more efficient Neurturin variants for treatment of Parkinson’s disease. Neurobiol Dis 2016; 96: 335-45.
[http://dx.doi.org/10.1016/j.nbd.2016.07.008] [PMID: 27425888]
[115]
Lindahl M, Saarma M, Lindholm P. 2017.
[116]
Parkash V, Lindholm P, Peränen J, et al. The structure of the conserved neurotrophic factors MANF and CDNF explains why they are bifunctional. Protein Eng Des Sel 2009; 22(4): 233-41.
[http://dx.doi.org/10.1093/protein/gzn080] [PMID: 19258449]
[117]
Apostolou A, Shen Y, Liang Y, Luo J, Fang S. Armet, a UPR-upregulated protein, inhibits cell proliferation and ER stress-induced cell death. Exp Cell Res 2008; 314(13): 2454-67.
[http://dx.doi.org/10.1016/j.yexcr.2008.05.001] [PMID: 18561914]
[118]
Lindahl M, Danilova T, Palm E, et al. MANF is indispensable for the proliferation and survival of pancreatic β cells. Cell Reports 2014; 7(2): 366-75.
[http://dx.doi.org/10.1016/j.celrep.2014.03. 023] [PMID: 24726366]
[119]
Pitale PM, Gorbatyuk O, Gorbatyuk M. Neurodegeneration: Keeping ATF4 on a Tight Leash. Front Cell Neurosci 2017; 11: 410.
[http://dx.doi.org/10.3389/fncel.2017.00410] [PMID: 29326555]
[120]
Chen YC, Sundvik M, Rozov S, Priyadarshini M, Panula P. MANF regulates dopaminergic neuron development in larval zebrafish. Dev Biol 2012; 370(2): 237-49.
[http://dx.doi.org/10. 1016/j.ydbio.2012.07.030] [PMID: 22898306]
[121]
Palgi M, Lindström R, Peränen J, Piepponen TP, Saarma M, Heino TI. Evidence that DmMANF is an invertebrate neurotrophic factor supporting dopaminergic neurons. Proc Natl Acad Sci USA 2009; 106(7): 2429-34.
[http://dx.doi.org/10.1073/pnas.0810996106] [PMID: 19164766]
[122]
Palgi M, Greco D, Lindström R, Auvinen P, Heino TI. Gene expression analysis of Drosophilaa Manf mutants reveals perturbations in membrane traffic and major metabolic changes. BMC Genomics 2012; 13(1): 134.
[http://dx.doi.org/10.1186/1471-2164-13-134] [PMID: 22494833]
[123]
Petrova P, Raibekas A, Pevsner J, et al. MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with selectivity for dopaminergic neurons. J Mol Neurosci 2003; 20(2): 173-88.
[http://dx.doi.org/10. 1385/JMN:20:2:173] [PMID: 12794311]
[124]
Lindholm P, Voutilainen MH, Laurén J, et al. Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo. Nature 2007; 448(7149): 73-7.
[http://dx.doi.org/ 10.1038/nature05957] [PMID: 17611540]
[125]
Voutilainen MH, Bäck S, Pörsti E, et al. Mesencephalic astrocyte-derived neurotrophic factor is neurorestorative in rat model of Parkinson’s disease. J Neurosci 2009; 29(30): 9651-9.
[http://dx.doi.org/10.1523/JNEUROSCI.0833-09.2009] [PMID: 19641128]
[126]
Airavaara M, Harvey BK, Voutilainen MH, et al. ; Hoffer B, Wang Y. CDNF protects the nigrostriatal dopamine system and promotes recovery after MPTP treatment in mice. Cell Transplant 2012; 21(6): 1213-23.
[http://dx.doi.org/10.3727/096368911X600948] [PMID: 21943517]
[127]
Bäck S, Peränen J, Galli E, et al. Gene therapy with AAV2-CDNF provides functional benefits in a rat model of Parkinson’s disease. Brain Behav 2013; 3(2): 75-88.
[http://dx.doi.org/10.1002/brb3. 117] [PMID: 23532969]
[128]
Ren X, Zhang T, Gong X, Hu G, Ding W, Wang X. AAV2-mediated striatum delivery of human CDNF prevents the deterioration of midbrain dopamine neurons in a 6-hydroxydopamine induced parkinsonian rat model. Exp Neurol 2013; 248: 148-56.
[http://dx.doi.org/10.1016/j.expneurol.2013.06.002] [PMID: 23764500]
[129]
Cordero-Llana Ó, Houghton BC, Rinaldi F, et al. Enhanced efficacy of the CDNF/MANF family by combined intranigral overexpression in the 6-OHDA rat model of Parkinson’s disease. Mol Ther 2015; 23(2): 244-54.
[http://dx.doi.org/10.1038/mt.2014. 206] [PMID: 25369767]
[130]
Subramanian K. Restoration of Motor and Non-Motor Functions by Neurotrophic Factors in Nonhuman Primates with Dopamine Depletion 2013.http://d-scholarship.pitt.edu/20301/
[131]
Voutilainen MH, Bäck S, Peränen J, et al. Chronic infusion of CDNF prevents 6-OHDA-induced deficits in a rat model of Parkinson’s disease. Exp Neurol 2011; 228(1): 99-108.
[http://dx.doi.org/dx. doi.org/10.1016/j.expneurol.2010.12.013] [PMID: 21185834]
[132]
Yasuhara T, Shingo T, Muraoka K, Kameda M, Agari T, Ji W. Y.; Hayase, H.; Hamada, H.; Borlongan, C.V.; Date, I. Neurorescue effects of VEGF on a rat model of Parkinson’s disease. Brain Res 2005; 1053(1-2): 10-8.
[http://dx.doi.org/10. 1016/j.brainres.2005.05.027] [PMID: 16045899]
[133]
Padel T, Özen I, Boix J, et al. Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson’s disease. Neurobiol Dis 2016; 94: 95-105.
[http://dx.doi.org/10.1016/j.nbd. 2016.06.002] [PMID: 27288154]
[134]
Yasuhara T, Shingo T, Muraoka K. wen Ji, Y.; Kameda, M.; Takeuchi, A.; Yano, A.; Nishio, S.; Matsui, T.; Miyoshi, Y.; Hamada, H.; Date, I. The differences between high and low-dose administration of VEGF to dopaminergic neurons of in vitro and in vivo Parkinson’s disease model. Brain Res 2005; 1038(1): 1-10.
[http://dx.doi.org/10.1016/j.brainres.2004.12.055] [PMID: 15748867]
[135]
Meng X, Lindahl M, Hyvönen ME, et al. Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science 2000; 287(5457): 1489-93.
[http://dx.doi.org/ 10.1126/science.287.5457.1489] [PMID: 10688798]
[136]
Bergmann O, Spalding KL, Frisén J. Adult Neurogenesis in Humans. Cold Spring Harb Perspect Biol 2015; 7(7): a018994.
[http://dx.doi.org/10.1101/cshperspect.a018994] [PMID: 26134318]
[137]
Sorrells SF, Paredes MF, Cebrian-Silla A, et al. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature 2018; 555(7696): 377-81.
[http://dx.doi.org/10.1038/nature25975] [PMID: 29513649]
[138]
Xie MQ, Chen ZC, Zhang P, et al. Newborn dopaminergic neurons are associated with the migration and differentiation of SVZ-derived neural progenitors in a 6-hydroxydopamin-injected mouse model. Neuroscience 2017; 352: 64-78.
[http://dx.doi.org/10.1016/j.neuroscience.2017. 03.045] [PMID: 28385636]
[139]
Krajnak K, Dahl R. Small molecule SUMOylation activators are novel neuroprotective agents. Bioorg Med Chem Lett 2017; 28(3): 405-9.
[http://dx.doi.org/10.1016/j.bmcl.2017.12.028] [PMID: 29269215]
[140]
Kim SM, Park YJ, Shin MS, et al. Acacetin inhibits neuronal cell death induced by 6-hydroxydopamine in cellular Parkinson’s disease model. Bioorg Med Chem Lett 2017; 27(23): 5207-12.
[http://dx.doi.org/10.1016/j.bmcl.2017.10.048] [PMID: 29089232]
[141]
Salakhutdinov NF, Volcho KP, Yarovaya OI. Monoterpenes as a Renewable Source of Biologically Active Compounds. Pure Appl Chem 2017; 89(8): 1105-17.
[http://dx.doi.org/10.1515/pac-2017-0109]
[142]
Santos CM, Santos M. New agents promote neuroprotection in Parkinson’s disease models. CNS Neurol Disord Drug Targets 2012; 11(4): 410-8.
[http://dx.doi.org/10.2174/187152712800792820] [PMID: 22483311]
[143]
Le Douaron G, Ferrié L, Sepulveda-Diaz JE, et al. New 6-Aminoquinoxaline Derivatives with Neuroprotective Effect on Dopaminergic Neurons in Cellular and Animal Parkinson Disease Models. J Med Chem 2016; 59(13): 6169-86.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00297] [PMID: 27341519]
[144]
Zhang Q, Chen S, Yu S, et al. Neuroprotective effects of pyrroloquinoline quinone against rotenone injury in primary cultured midbrain neurons and in a rat model of Parkinson’s disease. Neuropharmacology 2016; 108: 238-51.
[http://dx.doi.org/10.1016/j.neuropharm.2016.04.025] [PMID: 27108097]
[145]
Dati LM, Ulrich H, Real CC, Feng ZP, Sun HS, Britto LR. Carvacrol promotes neuroprotection in the mouse hemiparkinsonian model. Neuroscience 2017; 356: 176-81.
[http://dx.doi.org/dx.doi. org/10.1016/j.neuroscience.2017.05.013] [PMID: 28526576]
[146]
Guo Z, Xu S, Du N, Liu J, Huang Y, Han M. Neuroprotective effects of stemazole in the MPTP-induced acute model of Parkinson’s disease: Involvement of the dopamine system. Neurosci Lett 2016; 616: 152-9.
[http://dx.doi.org/10.1016/j.neulet. 2016.01.048] [PMID: 26827716]
[147]
Singh AK, Halder-Sinha S, Clement JP, Kundu TK. Epigenetic modulation by small molecule compounds for neurodegenerative disorders. Pharmacol Res 2018; 132(132): 135-48.
[http://dx.doi.org/ dx.doi.org/10.1016/j.phrs.2018.04.014] [PMID: 29684672]
[148]
O’Keeffe GC, Tyers P, Aarsland D, Dalley JW, Barker RA, Caldwell MA. Dopamine-induced proliferation of adult neural precursor cells in the mammalian subventricular zone is mediated through EGF. Proc Natl Acad Sci USA 2009; 106(21): 8754-9.
[http://dx.doi.org/10.1073/pnas.0803955106] [PMID: 19433789]
[149]
Van Kampen JM, Eckman CB. Dopamine D3 receptor agonist delivery to a model of Parkinson’s disease restores the nigrostriatal pathway and improves locomotor behavior. J Neurosci 2006; 26(27): 7272-80.
[http://dx.doi.org/10.1523/JNEUROSCI.0837-06.2006] [PMID: 16822985]
[150]
Milosevic J, Schwarz SC, Maisel M, et al. Dopamine D2/D3 receptor stimulation fails to promote dopaminergic neurogenesis of murine and human midbrain-derived neural precursor cells in vitro. Stem Cells Dev 2007; 16(4): 625-35.
[http://dx.doi.org/10.1089/scd. 2006.0113] [PMID: 17784836]
[151]
O’Keeffe GC, Barker RA, Caldwell MA. Dopaminergic modulation of neurogenesis in the subventricular zone of the adult brain. Cell Cycle 2009; 8(18): 2888-94.
[http://dx.doi.org/10. 4161/cc.8.18.9512] [PMID: 19713754]
[152]
Winner B, Desplats P, Hagl C, et al. Dopamine receptor activation promotes adult neurogenesis in an acute Parkinson model. Exp Neurol 2009; 219(2): 543-52.
[http://dx.doi.org/10.1016/j.expneurol.2009.07.013] [PMID: 19619535]
[153]
McCormack PL. Rasagiline: a review of its use in the treatment of idiopathic Parkinson’s disease. CNS Drugs 2014; 28(11): 1083-97.
[http://dx.doi.org/10.1007/s40263-014-0206-y] [PMID: 25322951]
[154]
Sagi Y, Mandel S, Amit T, Youdim MBH. Activation of tyrosine kinase receptor signaling pathway by rasagiline facilitates neurorescue and restoration of nigrostriatal dopamine neurons in post-MPTP-induced parkinsonism. Neurobiol Dis 2007; 25(1): 35-44.
[http://dx.doi.org/10.1016/j.nbd.2006.07.020] [PMID: 17055733]
[155]
Mandel SA, Sagi Y, Amit T. Rasagiline promotes regeneration of substantia nigra dopaminergic neurons in post-MPTP-induced Parkinsonism via activation of tyrosine kinase receptor signaling pathway. Neurochem Res 2007; 32(10): 1694-9.
[http://dx.doi.org/dx. doi.org/10.1007/s11064-007-9351-8] [PMID: 17701352]
[156]
Reznichenko L, Kalfon L, Amit T, Youdim MBH, Mandel SA. Low dosage of rasagiline and epigallocatechin gallate synergistically restored the nigrostriatal axis in MPTP-induced parkinsonism. Neurodegener Dis 2010; 7(4): 219-31.
[http://dx.doi.org/dx.doi. org/10.1159/000265946] [PMID: 20197647]
[157]
Olanow CW, Rascol O, Hauser R, et al. A double-blind, delayed-start trial of rasagiline in Parkinson’s disease. N Engl J Med 2009; 361(13): 1268-78.
[http://dx.doi.org/10.1056/NEJMoa0809335] [PMID: 19776408]
[158]
Youdim MBH. Rasagiline in Parkinson’s disease. N Engl J Med 2010; 362(7): 657-8.
[http://dx.doi.org/10.1056/NEJMc0910491] [PMID: 20164492]
[159]
Jang S-W, Liu X, Yepes M, et al. A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone. Proc Natl Acad Sci USA 2010; 107(6): 2687-92.
[http://dx.doi.org/10.1073/pnas.0913572107] [PMID: 20133810]
[160]
Nie S, Xu Y, Chen G, et al. Small molecule TrkB agonist deoxygedunin protects nigrostriatal dopaminergic neurons from 6-OHDA and MPTP induced neurotoxicity in rodents. Neuropharmacology 2015; 99: 448-58.
[http://dx.doi.org/10.1016/j.neuropharm.2015.08.016] [PMID: 26282118]
[161]
Luo D, Shi Y, Wang J, et al. 7,8-dihydroxyflavone protects 6-OHDA and MPTP induced dopaminergic neurons degeneration through activation of TrkB in rodents. Neurosci Lett 2016; 620: 43-9.
[http://dx.doi.org/dx.doi. org/10.1016/j.neulet.2016.03.042] [PMID: 27019033]
[162]
Li X-H, Dai C-F, Chen L, Zhou W-T, Han H-L, Dong Z-F. 7,8-dihydroxyflavone Ameliorates Motor Deficits Via Suppressing α-synuclein Expression and Oxidative Stress in the MPTP-induced Mouse Model of Parkinson’s Disease. CNS Neurosci Ther 2016; 22(7): 617-24.
[http://dx.doi.org/10.1111/cns.12555] [PMID: 27079181]
[163]
He J, Xiang Z, Zhu X, et al. Neuroprotective Effects of 7, 8-dihydroxyflavone on Midbrain Dopaminergic Neurons in MPP+-treated Monkeys. Sci Rep 2016; 6: 34339.
[http://dx.doi.org/10.1038/srep34339] [PMID: 27731318]
[164]
Boltaev U, Meyer Y, Tolibzoda F, et al. Multiplex Quantitative Assays Indicate a Need for Reevaluating Reported Small-Molecule TrkB Agonists 2017.
[165]
Wu CH, Hung TH, Chen CC, et al. Post-injury treatment with 7,8-dihydroxyflavone, a TrkB receptor agonist, protects against experimental traumatic brain injury via PI3K/Akt signaling. PLoS One 2014; 9(11): e113397.
[http://dx.doi.org/10.1371/journal.pone.0113397] [PMID: 25415296]
[166]
Sinyakova NA, Bazhenova EY, Bazovkina DV. Kulikov, A.V. Effect of the TrkB Antagonist-7,8-Dihydroxyflavone on Mice Serotonin System. Zh Vyssh Nerv Deiat Im I P Pavlova 2018; 68(1): 125-34.
[http://dx.doi.org/ DOI: 10.7868/S0044467718010100]
[167]
Chen J, Chua KW, Chua CC, et al. Antioxidant activity of 7,8-dihydroxyflavone provides neuroprotection against glutamate-induced toxicity. Neurosci Lett 2011; 499(3): 181-5.
[http://dx.doi.org/dx. doi.org/10.1016/j.neulet.2011.05.054] [PMID: 21651962]
[168]
Han X, Zhu S, Wang B, et al. Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity. Neurochem Int 2014; 64(1): 18-23.
[http://dx.doi.org/10.1016/j.neuint.2013.10. 018] [PMID: 24220540]
[169]
Spagnuolo C, Moccia S, Russo GL. Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur J Med Chem 2018; 153: 105-15.
[http://dx.doi.org/10.1016/j.ejmech.2017.09. 001] [PMID: 28923363]
[170]
Massa SM, Yang T, Xie Y, et al. Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents. J Clin Invest 2010; 120(5): 1774-85.
[http://dx.doi.org/dx. doi.org/10.1172/JCI41356] [PMID: 20407211]
[171]
Yang T.
[172]
Kowsky S, Pöppelmeyer C, Kramer ER, et al. RET signaling does not modulate MPTP toxicity but is required for regeneration of dopaminergic axon terminals. Proc Natl Acad Sci USA 2007; 104(50): 20049-54.
[http://dx.doi.org/10.1073/pnas.0706177104] [PMID: 18056810]
[173]
Drinkut A, Tillack K, Meka DP, Schulz JB, Kügler S, Kramer ER. Ret is essential to mediate GDNF’s neuroprotective and neuroregenerative effect in a Parkinson disease mouse model. Cell Death Dis 2016; 7(9): e2359.
[http://dx.doi.org/10.1038/cddis.2016.263] [PMID: 27607574]
[174]
Bespalov MM, Saarma M. GDNF family receptor complexes are emerging drug targets. Trends Pharmacol Sci 2007; 28(2): 68-74.
[http://dx.doi.org/10.1016/j.tips.2006.12.005] [PMID: 17218019]
[175]
Tokugawa K, Yamamoto K, Nishiguchi M, et al. XIB4035, a novel nonpeptidyl small molecule agonist for GFRalpha-1. Neurochem Int 2003; 42(1): 81-6.
[http://dx.doi.org/10.1016/S0197-0186(02)00053-0] [PMID: 12441171]
[176]
Hedstrom KL, Murtie JC, Albers K, Calcutt NA, Corfas G. Treating small fiber neuropathy by topical application of a small molecule modulator of ligand-induced GFRα/RET receptor signaling. Proc Natl Acad Sci USA 2014; 111(6): 2325-30.
[http://dx.doi.org/10.1073/pnas.1308889111] [PMID: 24449858]
[177]
Sidorova YA, Bespalov MM, Wong AW, et al. A novel small molecule gdnf receptor RET agonist, BT13, promotes neurite growth from sensory neurons in vitro and attenuates experimental neuropathy in the rat. Front Pharmacol 2017; 8(JUN): 365.
[PMID: 28680400]
[178]
Ivanova L, Tammiku-Taul J, Sidorova Y, Saarma M, Karelson M. Small-Molecule Ligands as Potential GDNF Family Receptor Agonists. ACS Omega 2018; 3(1): 1022-30.
[http://dx.doi.org/dx. doi.org/10.1021/acsomega.7b01932] [PMID: 30023796]
[179]
Gilligan PJ. Inhibitors of leucine-rich repeat kinase 2 (LRRK2): progress and promise for the treatment of Parkinson’s disease. Curr Top Med Chem 2015; 15(10): 927-38.
[http://dx.doi.org/ 10.2174/156802661510150328223655] [PMID: 25832719]
[180]
Salado IG, Zaldivar-Diez J, Sebastián-Pérez V, et al. Leucine rich repeat kinase 2 (LRRK2) inhibitors based on indolinone scaffold: Potential pro-neurogenic agents. Eur J Med Chem 2017; 138: 328-42.
[http://dx.doi.org/10.1016/j. ejmech.2017.06.060] [PMID: 28688273]
[181]
Liao GZ, Wang GY, Xu XL, Zhou GH. Effect of cooking methods on the formation of heterocyclic aromatic amines in chicken and duck breast. Meat Sci 2010; 85(1): 149-54.
[http://dx.doi.org/ dx.doi.org/10.1016/j.meatsci.2009.12.018] [PMID: 20374878]
[182]
Hamann J, Wernicke C, Lehmann J, Reichmann H, Rommelspacher H, Gille G. 9-Methyl-β-carboline up-regulates the appearance of differentiated dopaminergic neurones in primary mesencephalic culture. Neurochem Int 2008; 52(4-5): 688-700.
[http://dx.doi.org/ dx.doi.org/10.1016/j.neuint.2007.08.018] [PMID: 17913302]
[183]
Polanski W, Reichmann H, Gille G. Stimulation, protection and regeneration of dopaminergic neurons by 9-methyl-β-carboline: a new anti-Parkinson drug? Expert Rev Neurother 2011; 11(6): 845-60.
[http://dx.doi.org/10.1586/ern.11.1] [PMID: 21651332]
[184]
Polanski W, Enzensperger C, Reichmann H, Gille G. The exceptional properties of 9-methyl-β-carboline: stimulation, protection and regeneration of dopaminergic neurons coupled with anti-inflammatory effects. J Neurochem 2010; 113(6): 1659-75.
[PMID: 20374418]
[185]
Wernicke C, Hellmann J, Zieba B, et al. 9-Methyl-beta-carboline has restorative effects in an animal model of Parkinson’s disease. Pharmacol Rep 2010; 62(1): 35-53.
[http://dx.doi.org/ 10.1016/S1734-1140(10)70241-3] [PMID: 20360614]
[186]
Matsubara K, Gonda T, Sawada H, et al. Endogenously occurring beta-carboline induces parkinsonism in nonprimate animals: a possible causative protoxin in idiopathic Parkinson’s disease. J Neurochem 1998; 70(2): 727-35.
[http://dx.doi.org/10. 1046/j.1471-4159.1998.70020727.x] [PMID: 9453568]
[187]
De Jesús-Cortés H, Xu P, Drawbridge J, et al. Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of Parkinson disease. Proc Natl Acad Sci USA 2012; 109(42): 17010-5.
[http://dx.doi.org/dx.doi. org/10.1073/pnas.1213956109] [PMID: 23027934]
[188]
Pieper AA, Xie S, Capota E, et al. Discovery of a proneurogenic, neuroprotective chemical. Cell 2010; 142(1): 39-51.
[http://dx.doi.org/ 10.1016/j.cell.2010.06.018] [PMID: 20603013]
[189]
Garrett SM, Whitaker RM, Beeson CC, Schnellmann RG. Agonism of the 5-hydroxytryptamine 1F receptor promotes mitochondrial biogenesis and recovery from acute kidney injury. J Pharmacol Exp Ther 2014; 350(2): 257-64.
[http://dx.doi.org/ 10.1124/jpet.114.214700] [PMID: 24849926]
[190]
Scholpa NE, Lynn MK, Corum D, Boger HA, Schnellmann RG. 5-HT1F receptor-mediated mitochondrial biogenesis for the treatment of Parkinson’s disease. Br J Pharmacol 2018; 175(2): 348-58.
[http://dx.doi.org/10.1111/bph.14076] [PMID: 29057453]
[191]
Su C, Elfeki N, Ballerini P, et al. Guanosine improves motor behavior, reduces apoptosis, and stimulates neurogenesis in rats with parkinsonism. J Neurosci Res 2009; 87(3): 617-25.
[http://dx.doi.org/ dx.doi.org/10.1002/jnr.21883] [PMID: 18816792]

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