Treatment of Parkinson’s Disease by MAO-B Inhibitors, New Therapies and Future Challenges - A Mini-Review

Author(s): Della G.T. Parambi*

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 23 , Issue 9 , 2020


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Abstract:

Background: One of the most prevalent neurodegenerative diseases with increasing age is Parkinson’s disease (PD). Its pathogenesis is unclear and mainly confined to glutamate toxicity and oxidative stress. The dyskinesia and motor fluctuations and neuroprotective potential are the major concerns which are still unmet in PD therapy.

Objective: This article is a capsulization of the role of MAO-B in the treatment of PD, pharmacological properties, safety and efficiency, clinical evidence through random trials, future therapies and challenges.

Conclusion: MAO-B inhibitors are well tolerated for the treatment of PD because of their pharmacokinetic properties and neuroprotective action. Rasagiline and selegiline were recommended molecules for early PD and proven safe and provide a modest to significant rise in motor function, delay the use of levodopa and used in early PD. Moreover, safinamide is antiglutamatergic in action. When added to Levodopa, these molecules significantly reduce the offtime with a considerable improvement of non-motor symptoms. This review also discusses the new approaches in therapy like the use of biomarkers, neurorestorative growth factors, gene therapy, neuroimaging, neural transplantation, and nanotechnology. Clinical evidence illustrated that MAOB inhibitors are recommended as monotherapy and added on therapy to levodopa. A large study and further evidence are required in the field of future therapies to unwind the complexity of the disease.

Keywords: Parkinson's disease, rasagiline, selegiline, safinamide, MAO-B inhibitors, nanoparticles, genetherapy.

[1]
Obeso, J.A.; Rodríguez-Oroz, M.C.; Rodríguez, M.; Lanciego, J.L.; Artieda, J.; Gonzalo, N.; Olanow, C.W. Pathophysiology of the basal ganglia in Parkinson’s disease. Trends Neurosci., 2000, 23(10), S8-S19.
[http://dx.doi.org/10.1016/S1471-1931(00)00028-8] [PMID: 11052215]
[2]
Marvel, C.L.; Paradiso, S. Cognitive and neurological impairment in mood disorders. Psychiatr. Clin. North Am., 2004, 27(1), 19-36. [vii-viii.
[http://dx.doi.org/10.1016/S0193-953X(03)00106-0] [PMID: 15062628]
[3]
Smith, Y.; Wichmann, T.; Factor, S.A.; Delong, M.R. Parkinsons disease therapeutics: new developments and challenges since the introduction of levodopaNeuro psychopharmacol,, 2011, 37(1), 213-246.
[4]
Riederer, P.; Müller, T. Monoamine oxidase-B inhibitors in the treatment of Parkinson’s disease: clinical-pharmacological aspects. J. Neural Transm. (Vienna), 2018, 125(11), 1751-1757.
[http://dx.doi.org/10.1007/s00702-018-1876-2] [PMID: 29569037]
[5]
Carradori, S.; Secci, D.; Petzer, J.P. MAO inhibitors and their wider applications: a patent review. Expert Opin. Ther. Pat., 2018, 28(3), 211-226.
[http://dx.doi.org/10.1080/13543776.2018.1427735] [PMID: 29324067]
[6]
Pereira, E.A.C.; Aziz, T.Z. Surgical insights into Parkinson’s disease. J. R. Soc. Med., 2006, 99(5), 238-244.
[http://dx.doi.org/10.1177/014107680609900515] [PMID: 16672757]
[7]
Dauer, W.; Przedborski, S. Parkinsons disease. Neuron, 2003, 39(6), 889-909.
[http://dx.doi.org/10.1016/S0896-6273(03)00568-3] [PMID: 12971891]
[8]
Braak, H.; Del Tredici, K.; Rüb, U.; de Vos, R.A.; Jansen Steur, E.N.; Braak, E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol. Aging, 2003, 24(2), 197-211.
[http://dx.doi.org/10.1016/S0197-4580(02)00065-9] [PMID: 12498954]
[9]
Hirsch, E.C.; Jenner, P.; Przedborski, S. Pathogenesis of Parkinson’s disease. Mov. Disord., 2013, 28(1), 24-30.
[http://dx.doi.org/10.1002/mds.25032] [PMID: 22927094]
[10]
Surmeier, J. Faculty of 1000 Evaluation for PARIS (ZNF746) Repression of PGC-1alpha Contributes to Neurodegeneration in Parkinsons Disease. Cell, 2011, 144(5), 689-702.
[11]
Fox, S.H.; Katzenschlager, R.; Lim, S-Y.; Ravina, B.; Seppi, K.; Coelho, M.; Poewe, W.; Rascol, O.; Goetz, C.G.; Sampaio, C. The movement disorder society evidence-based medicine review update: treatments for the motor symptoms of Parkinson’s disease. Mov. Disord., 2011, 26(S3), S2-S41.
[http://dx.doi.org/10.1002/mds.23829] [PMID: 22021173]
[12]
Connolly, B.S.; Lang, A.E. Pharmacological treatment of Parkinson disease: a review. JAMA, 2014, 311(16), 1670-1683.
[http://dx.doi.org/10.1001/jama.2014.3654] [PMID: 24756517]
[13]
Lang, A.E.; Marras, C. Initiating dopaminergic treatment in Parkinson’s disease. Lancet, 2014, 384(9949), 1164-1166.
[http://dx.doi.org/10.1016/S0140-6736(14)60962-4] [PMID: 24928806]
[14]
Dézsi, L.; Vécsei, L. Safinamide for the treatment of Parkinson’s disease. Expert Opin. Investig. Drugs, 2014, 23(5), 729-742.
[http://dx.doi.org/10.1517/13543784.2014.897694] [PMID: 24650154]
[15]
Guglielmi, P.; Carradori, S.; Ammazzalorso, A.; Secci, D. Novel approaches to the discovery of selective human monoamine oxidase-B inhibitors: is there room for improvement? Expert Opin. Drug Discov., 2019, 14(10), 995-1035.
[http://dx.doi.org/10.1080/17460441.2019.1637415] [PMID: 31268358]
[16]
Van der Schyf, C.J.; Youdim, M.B.H. Multifunctional drugs as neurotherapeutics. Neurotherapeutics, 2009, 6(1), 1-3.
[http://dx.doi.org/10.1016/j.nurt.2008.11.001] [PMID: 19110194]
[17]
Morphy, R.; Rankovic, Z. Designing multiple ligands - medicinal chemistry strategies and challenges. Curr. Pharm. Des., 2009, 15(6), 587-600.
[http://dx.doi.org/10.2174/138161209787315594] [PMID: 19199984]
[18]
Sarkar, S.; Raymick, J.; Imam, S. Neuroprotective and Therapeutic Strategies against Parkinson’s disease: recent perspectives. Int. J. Mol. Sci., 2016, 17(6), 904.
[http://dx.doi.org/10.3390/ijms17060904] [PMID: 27338353]
[19]
Shulman, K.I.; Herrmann, N.; Walker, S.E. Current place of monoamine oxidase inhibitors in the treatment of depression. CNS Drugs, 2013, 27(10), 789-797.
[http://dx.doi.org/10.1007/s40263-013-0097-3] [PMID: 23934742]
[20]
Marti, J.S.; Kettler, R.; Prada, M.; Richards, J.G. Molecular neuroanatomy of MAO-A and MAO-B. J. Neural. Trans Suppl, 1990, 1990, 49-53.
[21]
Chiba, K.; Trevor, A.; Castagnoli, N., Jr Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase. Biochem. Biophys. Res. Commun., 1984, 120(2), 574-578.
[http://dx.doi.org/10.1016/0006-291X(84)91293-2] [PMID: 6428396]
[22]
Dézsi, L.; Vécsei, L. Clinical implications of irregular ADMET properties with levodopa and other antiparkinson’s drugs. Expert Opin. Drug Metab. Toxicol., 2014, 10(3), 409-424.
[http://dx.doi.org/10.1517/17425255.2014.878702] [PMID: 24437461]
[23]
Knoll, J.; Ecsery, Z.; Magyar, K.; Sátory, E. Novel (-)deprenyl-derived selective inhibitors of B-type monoamine oxidase. The relation of structure to their action. Biochem. Pharmacol., 1978, 27(13), 1739-1747.
[http://dx.doi.org/10.1016/0006-2952(78)90550-6] [PMID: 708454]
[24]
Teo, K.C.; Ho, S-L.C. Monoamine oxidase-B (MAO-B) inhibitors: implications for disease-modification in Parkinson’s disease. Transl. Neurodegener., 2013, 2(1), 19.
[http://dx.doi.org/10.1186/2047-9158-2-19] [PMID: 24011391]
[25]
Mathew, B.; Parambi, D.G.T.; Mathew, G.E.; Uddin, M.S.; Inasu, S.T.; Kim, H.; Marathakam, A.; Unnikrishnan, M.K.; Carradori, S. Emerging therapeutic potentials of dual-acting MAO and AChE inhibitors in Alzheimer’s and Parkinson’s diseases. Arch. Pharm. (Weinheim), 2019, 352(11)e1900177
[http://dx.doi.org/10.1002/ardp.201900177] [PMID: 31478569]
[26]
Mathew, B.; Baek, S.C.; Thomas Parambi, D.G.; Lee, J.P.; Mathew, G.E.; Jayanthi, S.; Vinod, D.; Rapheal, C.; Devikrishna, V.; Kondarath, S.S.; Uddin, M.S.; Kim, H. Potent and highly selective dual-targeting monoamine oxidase-B inhibitors: Fluorinated chalcones of morpholine versus imidazole. Arch. Pharm. (Weinheim), 2019, 352(4)e1800309
[http://dx.doi.org/10.1002/ardp.201800309] [PMID: 30663112]
[27]
Sasidharan, R.; Baek, S.C.; Sreedharannair Leelabaiamma, M.; Kim, H.; Mathew, B. Imidazole bearing chalcones as a new class of monoamine oxidase inhibitors. Biomed. Pharmacother., 2018, 106, 8-13.
[http://dx.doi.org/10.1016/j.biopha.2018.06.064] [PMID: 29940538]
[28]
Mathew, B.; Mathew, G.E.; Ucar, G.; Joy, M.; Nafna, E.K.; Lohidakshan, K.K.; Suresh, J. Monoamine oxidase inhibitory activity of methoxy-substituted chalcones.Int. J. Biol. Macromol., 2017, 104(Pt A), 1321-1329.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.05.162] [PMID: 28577983]
[29]
Suresh, J.; Baek, S.C.; Ramakrishnan, S.P.; Kim, H.; Mathew, B. Discovery of potent and reversible MAO-B inhibitors as furanochalcones. Int. J. Biol. Macromol., 2018, 108, 660-664.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.11.159] [PMID: 29195801]
[30]
Parambi, D.G.T.; Oh, J.M.; Baek, S.C.; Lee, J.P.; Tondo, A.R.; Nicolotti, O.; Kim, H.; Mathew, B. Design, synthesis and biological evaluation of oxygenated chalcones as potent and selective MAO-B inhibitors. Bioorg. Chem., 2019, 93103335
[http://dx.doi.org/10.1016/j.bioorg.2019.103335] [PMID: 31606547]
[31]
Mathew, B. Unraveling the structural requirements of chalcone chemistry towards monoamine oxidase inhibition. Cent. Nerv. Syst. Agents Med. Chem., 2019, 19(1), 6-7.
[http://dx.doi.org/10.2174/1871524919666190131160122] [PMID: 30706795]
[32]
Cruz-Monteagudo, M.; Borges, F.; Cordeiro, M.N.D.S.; Helguera, A.M.; Tejera, E. Paz-Y-Mino, C.; Sanchez-Rodriguez, A.; Perera-Sardina, Y.; Perez-Castillo, Y. Chemoinformatics profiling of the chromone nucleus as a MAO-B/A2AAR dual binding scaffold. Curr. Neuropharmacol., 2017, 15(8), 1117-1135.
[http://dx.doi.org/10.2174/1570159X15666170116145316] [PMID: 28093976]
[33]
Mathew, B.; Dev, S.; Joy, M.; Mathew, G.E.; Marathakam, A.; Krishnan, G.K. Refining the structural features of chromones as selective MAO-B inhibitors: exploration of combined pharmacophore-based 3D-QSAR and quantum chemical studies. ChemistrySelect, 2017, 2(35), 11645-11652.
[http://dx.doi.org/10.1002/slct.201701213]
[34]
Mathew, B.; Mathew, G.E.; Petzer, J.P.; Petzer, A. Structural exploration of synthetic chromones as selective MAO-B inhibitors: a mini review. Comb. Chem. High Throughput Screen., 2017, 20(6), 522-532.
[http://dx.doi.org/10.2174/1386207320666170227155517] [PMID: 28245770]
[35]
Costas-Lago, M.C.; Besada, P.; Rodríguez-Enríquez, F.; Viña, D.; Vilar, S.; Uriarte, E.; Borges, F.; Terán, C. Synthesis and structure-activity relationship study of novel 3-heteroarylcoumarins based on pyridazine scaffold as selective MAO-B inhibitors. Eur. J. Med. Chem., 2017, 139, 1-11.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.045] [PMID: 28797881]
[36]
Schapira, A.H. Monoamine oxidase B inhibitors for the treatment of Parkinsonʼs disease. CNS Drugs, 2011, 25(12), 1061-1071.
[http://dx.doi.org/10.2165/11596310-000000000-00000] [PMID: 22133327]
[37]
Tábi, T.; Szökő, E.; Vécsei, L.; Magyar, K. The pharmacokinetic evaluation of selegiline ODT for the treatment of Parkinson’s disease. Expert Opin. Drug Metab. Toxicol., 2013, 9(5), 629-636.
[http://dx.doi.org/10.1517/17425255.2013.781152] [PMID: 23506388]
[38]
Shin, H.S. Metabolism of selegiline in humans. Identification, excretion, and stereochemistry of urine metabolites. Drug Metab. Dispos., 1997, 25(6), 657-662.
[PMID: 9193866]
[39]
Magyar, K.; Pálfi, M.; Tábi, T.; Kalász, H.; Szende, B.; Szöko, E. Pharmacological aspects of (-)-deprenyl. Curr. Med. Chem., 2004, 11(15), 2017-2031.
[http://dx.doi.org/10.2174/0929867043364793] [PMID: 15279565]
[40]
Mahmood, I. Clinical pharmacokinetics and pharmacodynamics of selegiline. An update. Clin. Pharmacokinet., 1997, 33(2), 91-102.
[http://dx.doi.org/10.2165/00003088-199733020-00002] [PMID: 9260033]
[41]
Cohen, G.; Pasik, P.; Cohen, B.; Leist, A.; Mytilineou, C.; Yahr, M.D. Pargyline and deprenyl prevent the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in monkeys. Eur. J. Pharmacol., 1984, 106(1), 209-210.
[http://dx.doi.org/10.1016/0014-2999(84)90700-3] [PMID: 6442232]
[42]
Podurgiel, S.J.; Yohn, S.E.; Dortche, K.; Correa, M.; Salamone, J.D. The MAO-B inhibitor deprenyl reduces the oral tremor and the dopamine depletion induced by the VMAT-2 inhibitor tetrabenazine. Behav. Brain Res. 2016, 298(Pt B), 188-191.
[http://dx.doi.org/10.1016/j.bbr.2015.11.008] [PMID: 26590367]
[43]
Goldstein, D.S.; Jinsmaa, Y.; Sullivan, P.; Holmes, C.; Kopin, I.J.; Sharabi, Y. Comparison of monoamine oxidase inhibitors in decreasing production of the autotoxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde in PC12 Cells. J. Pharmacol. Exp. Ther., 2016, 356(2), 483-492.
[http://dx.doi.org/10.1124/jpet.115.230201] [PMID: 26574516]
[44]
Parkinson Study Group Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N. Engl. J. Med., 1993, 328(3), 176-183.
[http://dx.doi.org/10.1056/NEJM199301213280305] [PMID: 8417384]
[45]
Shoulson, I.; Oakes, D.; Fahn, S.; Lang, A.; Langston, J.W.; LeWitt, P.; Olanow, C.W.; Penney, J.B.; Tanner, C.; Kieburtz, K.; Rudolph, A. Parkinson Study Group. Impact of sustained deprenyl (selegiline) in levodopa-treated Parkinson’s disease: a randomized placebo-controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trial. Ann. Neurol., 2002, 51(5), 604-612.
[http://dx.doi.org/10.1002/ana.10191] [PMID: 12112107]
[46]
Dashtipour, K.; Chen, J.J.; Kani, C.; Bahjri, K.; Ghamsary, M. Clinical Outcomes in Patients with Parkinson’s Disease Treated with a Monoamine Oxidase Type-B inhibitor: A Cross-Sectional, Cohort Study. Pharmacotherapy, 2015, 35(7), 681-686.
[http://dx.doi.org/10.1002/phar.1611] [PMID: 26139574]
[47]
Kamakura, K.; Mochizuki, H.; Kaida, K.; Hirata, A.; Kanzaki, M.; Masaki, T.; Nakamura, R.; Motoyoshi, K. Therapeutic factors causing hallucination in Parkinson’s disease patients, especially those given selegiline. Parkinsonism Relat. Disord., 2004, 10(4), 235-242.
[http://dx.doi.org/10.1016/j.parkreldis.2004.01.006] [PMID: 15120098]
[48]
Klein, C.; Kömpf, D.; Pulkowski, U.; Moser, A.; Vieregge, P. A study of visual hallucinations in patients with Parkinson’s disease. J. Neurol., 1997, 244(6), 371-377.
[http://dx.doi.org/10.1007/s004150050104] [PMID: 9249622]
[49]
Lees, A.J. Parkinson’s Disease Research Group of the United Kingdom. Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson’s disease. BMJ, 1995, 311(7020), 1602-1607.
[http://dx.doi.org/10.1136/bmj.311.7020.1602] [PMID: 8555803]
[50]
Katzenschlager, R.; Head, J.; Schrag, A.; Ben-Shlomo, Y.; Evans, A.; Lees, A.J. Parkinson’s Disease Research Group of the United Kingdom. Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD. Neurology, 2008, 71(7), 474-480.
[http://dx.doi.org/10.1212/01.wnl.0000310812.43352.66] [PMID: 18579806]
[51]
Riederer, P.; Youdim, M.B.H. Monoamine oxidase activity and monoamine metabolism in brains of Parkinsonian patients treated with l-deprenyl. J. Neurochem., 1986, 46(5), 1359-1365.
[http://dx.doi.org/10.1111/j.1471-4159.1986.tb01747.x] [PMID: 2420928]
[52]
Richard, I.H.; Kurlan, R.; Tanner, C.; Factor, S.; Hubble, J.; Suchowersky, O.; Waters, C. Parkinson Study Group Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson’s disease. Neurology, 1997, 48(4), 1070-1077.
[http://dx.doi.org/10.1212/WNL.48.4.1070] [PMID: 9109902]
[53]
Chen, J.J.; Swope, D.M.; Dashtipour, K. Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinson’s disease. Clin. Ther., 2007, 29(9), 1825-1849.
[http://dx.doi.org/10.1016/j.clinthera.2007.09.021] [PMID: 18035186]
[54]
Thébault, J.J.; Guillaume, M.; Levy, R. Tolerability, safety, pharmacodynamics, and pharmacokinetics of rasagiline: a potent, selective, and irreversible monoamine oxidase type B inhibitor. Pharmacotherapy, 2004, 24(10), 1295-1305.
[http://dx.doi.org/10.1592/phco.24.14.1295.43156] [PMID: 15628826]
[55]
Schapira, A.H. Rasagiline in neurodegeneration. Exp. Neurol., 2008, 212(2), 255-257.
[http://dx.doi.org/10.1016/j.expneurol.2008.05.002] [PMID: 18571162]
[56]
Parkinson Study Group A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch. Neurol., 2002, 59(12), 1937-1943.
[http://dx.doi.org/10.1001/archneur.59.12.1937] [PMID: 12470183]
[57]
Parkinson Study Group A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch. Neurol., 2004, 61(4), 561-566.
[http://dx.doi.org/10.1001/archneur.61.4.561] [PMID: 15096406]
[58]
Hauser, R.A.; Lew, M.F.; Hurtig, H.I.; Ondo, W.G.; Wojcieszek, J.; Fitzer-Attas, C.J. TEMPO Open-label Study Group. Long-term outcome of early versus delayed rasagiline treatment in early Parkinson’s disease. Mov. Disord., 2009, 24(4), 564-573.
[http://dx.doi.org/10.1002/mds.22402] [PMID: 19086083]
[59]
Rascol, O.; Fitzer-Attas, C.J.; Hauser, R.; Jankovic, J.; Lang, A.; Langston, J.W.; Melamed, E.; Poewe, W.; Stocchi, F.; Tolosa, E.; Eyal, E.; Weiss, Y.M.; Olanow, C.W.A. A double-blind, delayed-start trial of rasagiline in Parkinson’s disease (the ADAGIO study): prespecified and post-hoc analyses of the need for additional therapies, changes in UPDRS scores, and non-motor outcomes. Lancet Neurol., 2011, 10(5), 415-423.
[http://dx.doi.org/10.1016/S1474-4422(11)70073-4] [PMID: 21482191]
[60]
Parkinson Study Group A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch. Neurol., 2005, 62(2), 241-248.
[http://dx.doi.org/10.1001/archneur.62.2.241] [PMID: 15710852]
[61]
Rascol, O.; Brooks, D.J.; Melamed, E.; Oertel, W.; Poewe, W.; Stocchi, F.; Tolosa, E. LARGO study group Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet, 2005, 365(9463), 947-954.
[http://dx.doi.org/10.1016/S0140-6736(05)71083-7] [PMID: 15766996]
[62]
Poewe, W.; Hauser, R.A.; Lang, A. ADAGIO Investigators Effects of rasagiline on the progression of nonmotor scores of the MDS-UPDRS. Mov. Disord., 2015, 30(4), 589-592.
[http://dx.doi.org/10.1002/mds.26124] [PMID: 25545629]
[63]
Korchounov, A.; Winter, Y.; Rössy, W. Combined beneficial effect of rasagiline on motor function and depression in de novo PD. Clin. Neuropharmacol., 2012, 35(3), 121-124.
[http://dx.doi.org/10.1097/WNF.0b013e31823b1da8] [PMID: 22561875]
[64]
Alvarez, M.V.; Grogan, P.M. Hyposmia in Parkinson’s disease. Psychiatry Clin. Neurosci., 2012, 66(4), 370-370.
[http://dx.doi.org/10.1111/j.1440-1819.2012.02339.x] [PMID: 22624744]
[65]
Hanagasi, H.A.; Gurvit, H.; Unsalan, P.; Horozoglu, H.; Tuncer, N.; Feyzioglu, A.; Gunal, D.I.; Yener, G.G.; Cakmur, R.; Sahin, H.A.; Emre, M. The effects of rasagiline on cognitive deficits in Parkinson’s disease patients without dementia: a randomized, double-blind, placebo-controlled, multicenter study. Mov. Disord., 2011, 26(10), 1851-1858.
[http://dx.doi.org/10.1002/mds.23738] [PMID: 21500280]
[66]
Chen, J.J.; Berchou, R.C. Rasagiline, a selective second-generation irreversible inhibitor of the monoamine oxidase type B, is effective in patients older and younger than 65 years of age with early-to advanced Parkinson’s disease. Pharmacotherapy, 24, 1448.
[67]
Goetz, C.G.; Schwid, S.R.; Eberly, S.W.; Oakes, D.; Shoulson, I. Parkinson Study Group TEMPO and PRESTO Investigators Safety of rasagiline in elderly patients with Parkinson disease. Neurology, 2006, 66(9), 1427-1429.
[http://dx.doi.org/10.1212/01.wnl.0000210692.95595.1c] [PMID: 16682679]
[68]
Panisset, M.; Chen, J.J.; Rhyee, S.H.; Conner, J.; Mathena, J. STACCATO study investigators Serotonin toxicity association with concomitant antidepressants and rasagiline treatment: retrospective study (STACCATO). Pharmacotherapy, 2014, 34(12), 1250-1258.
[http://dx.doi.org/10.1002/phar.1500] [PMID: 25314256]
[69]
Caccia, C.; Salvati, P.; Rossetti, S. Safinamide: modulation of dopaminergic and glutamatergic systems. Mov. Disord., 2008, 23, S22-S23.
[70]
Kupsch, A.; Sautter, J.; Götz, M.E.; Breithaupt, W.; Schwarz, J.; Youdim, M.B.H.; Riederer, P.; Gerlach, M.; Oertel, W.H. Monoamine oxidase-inhibition and MPTP-induced neurotoxicity in the non-human primate: comparison of rasagiline (TVP 1012) with selegiline. J. Neural Transm. (Vienna), 2001, 108(8-9), 985-1009.
[http://dx.doi.org/10.1007/s007020170018] [PMID: 11716151]
[71]
Leuratti, C.; Sardina, M.; Ventura, P.; Assandri, A.; Müller, M.; Brunner, M. Disposition and metabolism of safinamide, a novel drug for Parkinson’s disease, in healthy male volunteers. Pharmacology, 2013, 92(3-4), 207-216.
[http://dx.doi.org/10.1159/000354805] [PMID: 24136086]
[72]
Binda, C.; Wang, J.; Pisani, L.; Caccia, C.; Carotti, A.; Salvati, P.; Edmondson, D.E.; Mattevi, A. Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs. J. Med. Chem., 2007, 50(23), 5848-5852.
[http://dx.doi.org/10.1021/jm070677y] [PMID: 17915852]
[73]
Marzo, A.; Dal Bo, L.; Monti, N.C.; Crivelli, F.; Ismaili, S.; Caccia, C.; Cattaneo, C.; Fariello, R.G. Pharmacokinetics and pharmacodynamics of safinamide, a neuroprotectant with antiparkinsonian and anticonvulsant activity. Pharmacol. Res., 2004, 50(1), 77-85.
[http://dx.doi.org/10.1016/j.phrs.2003.12.004] [PMID: 15082032]
[74]
Caccia, C.; Maj, R.; Calabresi, M.; Maestroni, S.; Faravelli, L.; Curatolo, L.; Salvati, P.; Fariello, R.G. Safinamide: from molecular targets to a new anti-Parkinson drug. Neurology, 2006, 67(7), S18-S23.
[http://dx.doi.org/10.1212/WNL.67.7_suppl_2.S18] [PMID: 17030736]
[75]
Seithel-Keuth, A.; Johne, A.; Freisleben, A.; Kupas, K.; Lissy, M.; Krösser, S. Absolute bioavailability and effect of food on the disposition of safinamide immediate release tablets in healthy adult subjects. Clin. Pharmacol. Drug Dev., 2013, 2(1), 79-89.
[http://dx.doi.org/10.1002/cpdd.2] [PMID: 27121562]
[76]
Onofrj, M.; Bonanni, L.; Thomas, A. An expert opinion on safinamide in Parkinson’s disease. Expert Opin. Investig. Drugs, 2008, 17(7), 1115-1125.
[http://dx.doi.org/10.1517/13543784.17.7.1115] [PMID: 18549347]
[77]
Schapira, A.H. Safinamide in the treatment of Parkinson’s disease. Expert Opin. Pharmacother., 2010, 11(13), 2261-2268.
[http://dx.doi.org/10.1517/14656566.2010.511612] [PMID: 20707760]
[78]
Kulisevsky, J. Emerging role of safinamide in Parkinson’s disease therapy. Eur. Neurol. Rev., 2014, 9, 108-112.
[http://dx.doi.org/10.17925/ENR.2014.09.02.108]
[79]
Müller, T. Current status of safinamide for the drug portfolio of Parkinson’s disease therapy. Expert Rev. Neurother., 2013, 13(9), 969-977.
[http://dx.doi.org/10.1586/14737175.2013.827488] [PMID: 24053341]
[80]
Stocchi, F.; Torti, M. Adjuvant therapies for Parkinson disease: critical evaluation of safinamide. Drug Des. Devel. Ther., 2016, 609-618.
[81]
Borgohain, R.; Szasz, J.; Stanzione, P.; Meshram, C.; Bhatt, M.; Chirilineau, D.; Stocchi, F.; Lucini, V.; Giuliani, R.; Forrest, E.; Rice, P.; Anand, R. undefined, undefined. Randomized trial of safinamide add-on to levodopa in parkinsons disease with motor fluctuations. Mov. Disord., 2014, 29(2), 229-237.
[http://dx.doi.org/10.1002/mds.25751] [PMID: 24323641]
[82]
Borgohain, R.; Szasz, J.; Stanzione, P.; Meshram, C.; Bhatt, M.H.; Chirilineau, D.; Stocchi, F.; Lucini, V.; Giuliani, R.; Forrest, E.; Rice, P.; Anand, R. Study 018 Investigators Two-year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson’s disease. Mov. Disord., 2014, 29(10), 1273-1280.
[http://dx.doi.org/10.1002/mds.25961] [PMID: 25044402]
[83]
Cattaneo, C.; Ferla, R.L.; Müller, E.; Sardina, M. Favourable effect of safinamide on mood over 2-year treatment of fluctuating Parkinson’s disease patients. Parkinsonism Relat. Disord., 2016, 22, 98-99.
[http://dx.doi.org/10.1016/j.parkreldis.2015.10.211]
[84]
Schnitker, J.; Müller, T. Meta-analysis of placebo-controlled clinical trials of safinamide and entacapone as add-on therapy to levodopa in the treatment of Parkinson’s disease. Eur. Neurol. Rev., 2015, 10(01), 15-22.
[http://dx.doi.org/10.17925/ENR.2015.10.01.15]
[85]
Cattaneo, C.; Sardina, M.; Bonizzoni, E. Safinamide as add-on therapy to levodopa in mid- to late-stage Parkinson’s disease fluctuating patients: post hoc analyses of studies 016 and SETTLE. J. Parkinsons Dis., 2016, 6(1), 165-173.
[http://dx.doi.org/10.3233/JPD-150700] [PMID: 26889632]
[86]
Cattaneo, C.; Caccia, C.; Marzo, A.; Maj, R.; Fariello, R.G. Pressor response to intravenous tyramine in healthy subjects after safinamide, a novel neuroprotectant with selective, reversible monoamine oxidase B inhibition. Clin. Neuropharmacol., 2003, 26(4), 213-217.
[http://dx.doi.org/10.1097/00002826-200307000-00012] [PMID: 12897643]
[87]
Youdim, M.B.; Kupershmidt, L.; Amit, T.; Weinreb, O. Promises of novel multi-target neuroprotective and neurorestorative drugs for Parkinson’s disease. Parkinsonism Relat. Disord., 2014, 20(Suppl. 1), S132-S136.
[http://dx.doi.org/10.1016/S1353-8020(13)70032-4] [PMID: 24262165]
[88]
Zheng, H.; Gal, S.; Weiner, L.M.; Bar-Am, O.; Warshawsky, A.; Fridkin, M.; Youdim, M.B.H. Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition. J. Neurochem., 2005, 95(1), 68-78.
[http://dx.doi.org/10.1111/j.1471-4159.2005.03340.x] [PMID: 16181413]
[89]
Youdim, M.B. M30, a brain permeable multitarget neurorestorative drug in post nigrostriatal dopamine neuron lesion of parkinsonism animal models. Parkinsonism Relat. Disord., 2012, 18(Suppl. 1), S151-S154.
[http://dx.doi.org/10.1016/S1353-8020(11)70047-5] [PMID: 22166418]
[90]
Liu, Z.; Cai, W.; Lang, M.; Yan, R.; Li, Z.; Zhang, G.; Yu, P.; Wang, Y.; Sun, Y.; Zhang, Z. Neuroprotective effects and mechanisms of action of multifunctional agents targeting free radicals, monoamine oxidase B and cholinesterase in Parkinson’s disease model. J. Mol. Neurosci., 2017, 61(4), 498-510.
[http://dx.doi.org/10.1007/s12031-017-0891-3] [PMID: 28144826]
[91]
Simola, N.; Morelli, M.; Pinna, A. Adenosine A2A receptor antagonists and Parkinson’s disease: state of the art and future directions. Curr. Pharm. Des., 2008, 14(15), 1475-1489.
[http://dx.doi.org/10.2174/138161208784480072] [PMID: 18537671]
[92]
Vlok, N.; Malan, S.F.; Castagnoli, N., Jr; Bergh, J.J.; Petzer, J.P. Inhibition of monoamine oxidase B by analogues of the adenosine A2A receptor antagonist (E)-8-(3-chlorostyryl)caffeine (CSC). Bioorg. Med. Chem., 2006, 14(10), 3512-3521.
[http://dx.doi.org/10.1016/j.bmc.2006.01.011] [PMID: 16442801]
[93]
Pretorius, J.; Malan, S.F.; Castagnoli, N., Jr; Bergh, J.J.; Petzer, J.P. Dual inhibition of monoamine oxidase B and antagonism of the adenosine A(2A) receptor by (E,E)-8-(4-phenylbutadien-1-yl)caffeine analogues. Bioorg. Med. Chem., 2008, 16(18), 8676-8684.
[http://dx.doi.org/10.1016/j.bmc.2008.07.088] [PMID: 18723354]
[94]
Petzer, J.P.; Castagnoli, N., Jr; Schwarzschild, M.A.; Chen, J-F.; Van der Schyf, C.J. Dual-target-directed drugs that block monoamine oxidase B and adenosine A(2A) receptors for Parkinson’s disease. Neurotherapeutics, 2009, 6(1), 141-151.
[http://dx.doi.org/10.1016/j.nurt.2008.10.035] [PMID: 19110205]
[95]
Brunschweiger, A.; Koch, P.; Schlenk, M.; Rafehi, M.; Radjainia, H.; Küppers, P.; Hinz, S.; Pineda, F.; Wiese, M.; Hockemeyer, J.; Heer, J.; Denonne, F.; Müller, C.E. 8-Substituted 1,3-dimethyltetrahydropyrazino[2,1-f]purinediones: Water-soluble adenosine receptor antagonists and monoamine oxidase B inhibitors. Bioorg. Med. Chem., 2016, 24(21), 5462-5480.
[http://dx.doi.org/10.1016/j.bmc.2016.09.003] [PMID: 27658798]
[96]
Stössel, A.; Schlenk, M.; Hinz, S.; Küppers, P.; Heer, J.; Gütschow, M.; Müller, C.E. Dual targeting of adenosine A(2A) receptors and monoamine oxidase B by 4H-3,1-benzothiazin-4-ones. J. Med. Chem., 2013, 56(11), 4580-4596.
[http://dx.doi.org/10.1021/jm400336x] [PMID: 23631427]
[97]
Haehner, A.; Boesveldt, S.; Berendse, H.W.; Mackay-Sim, A.; Fleischmann, J.; Silburn, P.A.; Johnston, A.N.; Mellick, G.D.; Herting, B.; Reichmann, H.; Hummel, T. Prevalence of smell loss in Parkinson’s disease--a multicenter study. Parkinsonism Relat. Disord., 2009, 15(7), 490-494.
[98]
Haehner, A.; Hummel, T.; Hummel, C.; Sommer, U.; Junghanns, S.; Reichmann, H. Olfactory loss may be a first sign of idiopathic Parkinson’s disease. Mov. Disord., 2007, 22(6), 839-842.
[http://dx.doi.org/10.1002/mds.21413] [PMID: 17357143]
[99]
Haehner, A.; Hummel, T.; Reichmann, H. Olfactory dysfunction as a diagnostic marker for Parkinson’s disease. Expert Rev. Neurother., 2009, 9(12), 1773-1779.
[http://dx.doi.org/10.1586/ern.09.115] [PMID: 19951136]
[100]
Marek, K.; Jennings, D. Can we image premotor Parkinson disease? Neurology, 2009, 72(7)(Suppl.), S21-S26.
[http://dx.doi.org/10.1212/WNL.0b013e318198df97] [PMID: 19221310]
[101]
Morley, J.F.; Duda, J.E. Olfaction as a biomarker in Parkinson’s disease. Biomarkers Med., 2010, 4(5), 661-670.
[http://dx.doi.org/10.2217/bmm.10.95] [PMID: 20945979]
[102]
Piccini, P.; Whone, A. Functional brain imaging in the differential diagnosis of Parkinson’s disease. Lancet Neurol., 2004, 3(5), 284-290.
[http://dx.doi.org/10.1016/S1474-4422(04)00736-7] [PMID: 15099543]
[103]
Lang, A.E.; Mikulis, D. A new sensitive imaging biomarker for Parkinson disease? Neurology, 2009, 72(16), 1374-1375.
[http://dx.doi.org/10.1212/01.wnl.0000343512.36654.41] [PMID: 19129504]
[104]
Kägi, G.; Bhatia, K.P.; Tolosa, E. The role of DAT-SPECT in movement disorders. J. Neurol. Neurosurg. Psychiatry, 2010, 81(1), 5-12.
[http://dx.doi.org/10.1136/jnnp.2008.157370] [PMID: 20019219]
[105]
Langston, J.W. The Parkinson’s complex: parkinsonism is just the tip of the iceberg. Ann. Neurol., 2006, 59(4), 591-596.
[http://dx.doi.org/10.1002/ana.20834] [PMID: 16566021]
[106]
Tolosa, E. Movement disorders: advances on many fronts. Lancet Neurol., 2007, 6(1), 7-8.
[http://dx.doi.org/10.1016/S1474-4422(06)70661-5] [PMID: 17166790]
[107]
Tolosa, E.; Compta, Y.; Gaig, C. The premotor phase of Parkinson’s disease. Parkinsonism Relat. Disord., 2007, 13(Suppl.), S2-S7.
[http://dx.doi.org/10.1016/j.parkreldis.2007.06.007] [PMID: 17681839]
[108]
Antoniades, C.A.; Barker, R.A. The search for biomarkers in Parkinson’s disease: a critical review. Expert Rev. Neurother., 2008, 8(12), 1841-1852.
[http://dx.doi.org/10.1586/14737175.8.12.1841] [PMID: 19086880]
[109]
Caudle, W.M.; Bammler, T.K.; Lin, Y.; Pan, S.; Zhang, J. Using ‘omics’ to define pathogenesis and biomarkers of Parkinson’s disease. Expert Rev. Neurother., 2010, 10(6), 925-942.
[http://dx.doi.org/10.1586/ern.10.54] [PMID: 20518609]
[110]
Aron, L.; Klein, R. Repairing the parkinsonian brain with neurotrophic factors. Trends Neurosci., 2011, 34(2), 88-100.
[http://dx.doi.org/10.1016/j.tins.2010.11.001] [PMID: 21144600]
[111]
Lang, A.E.; Gill, S.; Patel, N.K.; Lozano, A.; Nutt, J.G.; Penn, R.; Brooks, D.J.; Hotton, G.; Moro, E.; Heywood, P.; Brodsky, M.A.; Burchiel, K.; Kelly, P.; Dalvi, A.; Scott, B.; Stacy, M.; Turner, D.; Wooten, V.G.F.; Elias, W.J.; Laws, E.R.; Dhawan, V.; Stoessl, A.J.; Matcham, J.; Coffey, R.J.; Traub, M. Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease. Ann. Neurol., 2006, 59(3), 459-466.
[http://dx.doi.org/10.1002/ana.20737] [PMID: 16429411]
[112]
Baekelandt, V.; De Strooper, B.; Nuttin, B.; Debyser, Z. Gene therapeutic strategies for neurodegenerative diseases. Curr. Opin. Mol. Ther., 2000, 2(5), 540-554.
[PMID: 11249757]
[113]
Björklund, T.; Cederfjäll, E.A.; Kirik, D. Gene therapy for dopamine replacement. Prog. Brain Res., 2010, 184, 221-235.
[PMID: 20887878]
[114]
Feng, L.R.; Maguire-Zeiss, K.A. Gene therapy in Parkinsonʼs disease. CNS Drugs, 2010, 24(3), 177-192.
[http://dx.doi.org/10.2165/11533740-000000000-00000] [PMID: 20155994]
[115]
Kaplitt, M.G.; Feigin, A.; Tang, C.; Fitzsimons, H.L.; Mattis, P.; Lawlor, P.A.; Bland, R.J.; Young, D.; Strybing, K.; Eidelberg, D.; During, M.J. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, phase I trial. Lancet, 2007, 369(9579), 2097-2105.
[http://dx.doi.org/10.1016/S0140-6736(07)60982-9] [PMID: 17586305]
[116]
LeWitt, P.A.; Rezai, A.R.; Leehey, M.A.; Ojemann, S.G.; Flaherty, A.W.; Eskandar, E.N.; Kostyk, S.K.; Thomas, K.; Sarkar, A.; Siddiqui, M.S.; Tatter, S.B.; Schwalb, J.M.; Poston, K.L.; Henderson, J.M.; Kurlan, R.M.; Richard, I.H.; Van Meter, L.; Sapan, C.V.; During, M.J.; Kaplitt, M.G.; Feigin, A. AAV2-GAD gene therapy for advanced Parkinson’s disease: a double-blind, sham-surgery controlled, randomised trial. Lancet Neurol., 2011, 10(4), 309-319.
[http://dx.doi.org/10.1016/S1474-4422(11)70039-4] [PMID: 21419704]
[117]
Eberling, J.L.; Jagust, W.J.; Christine, C.W.; Starr, P.; Larson, P.; Bankiewicz, K.S.; Aminoff, M.J. Results from a phase I safety trial of hAADC gene therapy for Parkinson disease. Neurology, 2008, 70(21), 1980-1983.
[http://dx.doi.org/10.1212/01.wnl.0000312381.29287.ff] [PMID: 18401019]
[118]
Christine, C.W.; Starr, P.A.; Larson, P.S.; Eberling, J.L.; Jagust, W.J.; Hawkins, R.A.; VanBrocklin, H.F.; Wright, J.F.; Bankiewicz, K.S.; Aminoff, M.J. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology, 2009, 73(20), 1662-1669.
[http://dx.doi.org/10.1212/WNL.0b013e3181c29356] [PMID: 19828868]
[119]
Chang, V.C.; Chou, K.L. Deep brain stimulation for Parkinson’s disease: patient selection and motor outcomes. Med. Health R. I., 2006, 89(4), 142-144.
[PMID: 16676911]
[120]
Bronstein, J.M.; Tagliati, M.; Alterman, R.L.; Lozano, A.M.; Volkmann, J.; Stefani, A.; Horak, F.B.; Okun, M.S.; Foote, K.D.; Krack, P.; Pahwa, R.; Henderson, J.M.; Hariz, M.I.; Bakay, R.A.; Rezai, A.; Marks, W.J., Jr; Moro, E.; Vitek, J.L.; Weaver, F.M.; Gross, R.E.; DeLong, M.R. Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues. Arch. Neurol., 2011, 68(2), 165.
[http://dx.doi.org/10.1001/archneurol.2010.260] [PMID: 20937936]
[121]
Brundin, P.; Barker, R.A.; Parmar, M. Neural grafting in Parkinson’s disease Problems and possibilities.Prog. Brain Res; , 2010, 184, pp. 265-294.
[http://dx.doi.org/10.1016/S0079-6123(10)84014-2] [PMID: 20887880]
[122]
Freed, C.R.; Greene, P.E.; Breeze, R.E.; Tsai, W-Y.; DuMouchel, W.; Kao, R.; Dillon, S.; Winfield, H.; Culver, S.; Trojanowski, J.Q.; Eidelberg, D.; Fahn, S. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N. Engl. J. Med., 2001, 344(10), 710-719.
[http://dx.doi.org/10.1056/NEJM200103083441002] [PMID: 11236774]
[123]
Kordower, J.H.; Chu, Y.; Hauser, R.A.; Freeman, T.B.; Olanow, C.W. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat. Med., 2008, 14(5), 504-506.
[http://dx.doi.org/10.1038/nm1747] [PMID: 18391962]
[124]
Kordower, J.H.; Chu, Y.; Hauser, R.A.; Olanow, C.W.; Freeman, T.B. Transplanted dopaminergic neurons develop PD pathologic changes: a second case report. Mov. Disord., 2008, 23(16), 2303-2306.
[http://dx.doi.org/10.1002/mds.22369] [PMID: 19006193]
[125]
Björklund, T.; Carlsson, T.; Cederfjäll, E.A.; Carta, M.; Kirik, D. Optimized adeno-associated viral vector-mediated striatal DOPA delivery restores sensorimotor function and prevents dyskinesias in a model of advanced Parkinson’s disease. Brain, 2010, 133(Pt 2), 496-511.
[http://dx.doi.org/10.1093/brain/awp314] [PMID: 20129936]
[126]
Kaushik, A.C.; Bharadwaj, S.; Kumar, S.; Wei, D-Q. Nano-particle mediated inhibition of Parkinson’s disease using computational biology approach. Sci. Rep., 2018, 8(1), 9169.
[http://dx.doi.org/10.1038/s41598-018-27580-1] [PMID: 29907754]
[127]
Álvarez, Y.D.; Fauerbach, J.A.; Pellegrotti, J.V.; Jovin, T.M.; Jares-Erijman, E.A.; Stefani, F.D. Influence of gold nanoparticles on the kinetics of α-synuclein aggregation. Nano Lett., 2013, 13(12), 6156-6163.
[http://dx.doi.org/10.1021/nl403490e] [PMID: 24219503]
[128]
Schubert, D.; Dargusch, R.; Raitano, J.; Chan, S-W. Cerium and yttrium oxide nanoparticles are neuroprotective. Biochem. Biophys. Res. Commun., 2006, 342(1), 86-91.
[http://dx.doi.org/10.1016/j.bbrc.2006.01.129] [PMID: 16480682]
[129]
Mahmoudi, M.; Akhavan, O.; Ghavami, M.; Rezaee, F.; Ghiasi, S.M.A. Graphene oxide strongly inhibits amyloid beta fibrillation. Nanoscale, 2012, 4(23), 7322-7325.
[http://dx.doi.org/10.1039/c2nr31657a] [PMID: 23079862]
[130]
Padmanabhan, P.; Kumar, A.; Kumar, S.; Chaudhary, R.K.; Gulyás, B. Nanoparticles in practice for molecular-imaging applications: An overview. Acta Biomater., 2016, 41, 1-16.
[http://dx.doi.org/10.1016/j.actbio.2016.06.003] [PMID: 27265153]
[131]
Mirsadeghi, S.; Dinarvand, R.; Ghahremani, M.H.; Hormozi-Nezhad, M.R.; Mahmoudi, Z.; Hajipour, M.J.; Atyabi, F.; Ghavami, M.; Mahmoudi, M. Protein corona composition of gold nanoparticles/nanorods affects amyloid beta fibrillation process. Nanoscale, 2015, 7(11), 5004-5013.
[http://dx.doi.org/10.1039/C4NR06009A] [PMID: 25695421]
[132]
Harilal, S.; Jose, J.; Parambi, D.G.T.; Kumar, R.; Mathew, G.E.; Uddin, M.S.; Kim, H.; Mathew, B. Advancements in nanotherapeutics for Alzheimer’s disease: current perspectives. J. Pharm. Pharmacol., 2019, 71(9), 1370-1383.
[http://dx.doi.org/10.1111/jphp.13132] [PMID: 31304982]
[133]
Lang, A.E.; Espay, A.J. Disease modification in Parkinson’s disease: current approaches, challenges, and future considerations. Mov. Disord., 2018, 33(5), 660-677.
[http://dx.doi.org/10.1002/mds.27360] [PMID: 29644751]
[134]
Kalia, L.V.; Lang, A.E. Parkinson’s disease. Lancet, 2015, 386(9996), 896-912.
[http://dx.doi.org/10.1016/S0140-6736(14)61393-3] [PMID: 25904081]
[135]
Poewe, W.; Seppi, K.; Tanner, C.M.; Halliday, G.M.; Brundin, P.; Volkmann, J.; Schrag, A-E.; Lang, A.E. Parkinson disease. Nat. Rev. Dis. Primers, 2017, 3(1), 17013.
[http://dx.doi.org/10.1038/nrdp.2017.13] [PMID: 28332488]
[136]
Obeso, J.A.; Jon Stoessl, A.; Stamelou, M. Editors’ note: The 200th anniversary of the shaking palsy. Mov. Disord., 2017, 32(1), 1-1.
[http://dx.doi.org/10.1002/mds.26904] [PMID: 28124430]
[137]
Dijkstra, A.A.; Voorn, P.; Berendse, H.W.; Groenewegen, H.J.; Rozemuller, A.J.; van de Berg, W.D. Netherlands brain bank. Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson’s disease. Mov. Disord., 2014, 29(10), 1244-1251.
[http://dx.doi.org/10.1002/mds.25952] [PMID: 24996051]
[138]
Pickrell, A.M.; Youle, R.J. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron, 2015, 85(2), 257-273.
[http://dx.doi.org/10.1016/j.neuron.2014.12.007] [PMID: 25611507]
[139]
Visanji, N.P.; Brotchie, J.M.; Kalia, L.V.; Koprich, J.B.; Tandon, A.; Watts, J.C.; Lang, A.E. α-Synuclein-based animal models of Parkinson’s disease: challenges and opportunities in a new era. Trends Neurosci., 2016, 39(11), 750-762.
[http://dx.doi.org/10.1016/j.tins.2016.09.003] [PMID: 27776749]
[140]
McCann, H.; Cartwright, H.; Halliday, G.M. Neuropathology of α-synuclein propagation and braak hypothesis. Mov. Disord., 2016, 31(2), 152-160.
[http://dx.doi.org/10.1002/mds.26421] [PMID: 26340605]
[141]
Athauda, D.; Foltynie, T. Challenges in detecting disease modification in Parkinson’s disease clinical trials. Parkinsonism Relat. Disord., 2016, 32, 1-11.
[http://dx.doi.org/10.1016/j.parkreldis.2016.07.019] [PMID: 27499048]
[142]
Thibault, L.; Rascol, O.; Corvol, J-C.; Ferreira, J.; Defebvre, L.; Deplanque, D.; Bordet, R.; Moreau, C.; Devos, D. New perspectives on study designs for evaluating neuroprotection in Parkinson’s disease. Mov. Disord., 2017, 32(10), 1365-1370.
[http://dx.doi.org/10.1002/mds.27055] [PMID: 28703395]
[143]
Espay, A.J.; Schwarzschild, M.A.; Tanner, C.M.; Fernandez, H.H.; Simon, D.K.; Leverenz, J.B.; Merola, A.; Chen-Plotkin, A.; Brundin, P.; Kauffman, M.A.; Erro, R.; Kieburtz, K.; Woo, D.; Macklin, E.A.; Standaert, D.G.; Lang, A.E. Biomarker-driven phenotyping in Parkinson’s disease: A translational missing link in disease-modifying clinical trials. Mov. Disord., 2017, 32(3), 319-324.
[http://dx.doi.org/10.1002/mds.26913] [PMID: 28233927]
[144]
Wong, Y.C.; Krainc, D. α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies. Nat. Med., 2017, 23(2), 1-13.
[http://dx.doi.org/10.1038/nm.4269] [PMID: 28170377]
[145]
Biglan, K.M.; Oakes, D.; Lang, A.E.; Hauser, R.A.; Hodgeman, K.; Greco, B.; Lowell, J.; Rockhill, R.; Shoulson, I.; Venuto, C.; Young, D.; Simuni, T. Parkinson Study Group STEADY‐PD III Investigators A novel design of a Phase III trial of isradipine in early Parkinson disease (STEADY-PD III). Ann. Clin. Transl. Neurol., 2017, 4(6), 360-368.
[http://dx.doi.org/10.1002/acn3.412] [PMID: 28589163]


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