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Neuroprotection in Parkinson Disease

  • Kewal K. Jain
Chapter

Abstract

Parkinson’s disease (PD) is a progressive disorder of the CNS characterized by tremor at rest, bradykinesia (slowness of movement), rigidity and flexed posture. Pathologically, the key deficit is loss of pigmented dopamine-producing neurons in the substantia nigra. Although the cause of the disease remains unknown, considerable progress has been made to expand our knowledge of the clinical features, neuropathology and treatment of the disease since the description of the disease by James Parkinson about 200 years ago.

References

  1. Ahlskog JE, Uitti RJ. Rasagiline, Parkinson neuroprotection, and delayed-start trials: still no satisfaction? Neurology 2010;74:1143–8.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Akaike A, Takada-Takatori Y, Kume T, Izumi Y. Mechanisms of neuroprotective effects of nicotine and acetylcholinesterase inhibitors: role of alpha4 and alpha7 receptors in neuroprotection. J Mol Neurosci 2010;40:211–6.PubMedCrossRefGoogle Scholar
  3. Alberts JL, Linder SM, Penko AL, et al. It is not about the bike, it is about the pedaling: forced exercise and Parkinson’s disease. Exerc Sport Sci Rev 2011;39:177–86.PubMedGoogle Scholar
  4. Albrecht S, Buerger E. Potential neuroprotection mechanisms in PD: focus on dopamine agonist pramipexole. Curr Med Res Opin 2009;25:2977–87.PubMedCrossRefGoogle Scholar
  5. Aleyasin H, Rousseaux MW, Marcogliese PC, et al. DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway. PNAS 2010;107:3186–91.PubMedCrossRefGoogle Scholar
  6. Allen PJ, Feigin A. Gene-based therapies in Parkinson’s disease. Neurotherapeutics 2014;11:60–7.PubMedCrossRefGoogle Scholar
  7. Androutsellis-Theotokis A, Rueger MA, Mkhikian H, et al. Targeting neural precursors in the adult brain rescues injured dopamine neurons. PNAS 2009;106:13570–5.PubMedCrossRefGoogle Scholar
  8. Bar-Am O, Weinreb O, Amit T, Youdim MB. The neuroprotective mechanism of 1-(R)-aminoindan, the major metabolite of the anti-parkinsonian drug rasagiline. J Neurochem 2010;112:1131–7.PubMedCrossRefGoogle Scholar
  9. Bartus RT, Baumann TL, Brown L, et al. Advancing neurotrophic factors as treatments for age-related neurodegenerative diseases: developing and demonstrating “clinical proof-of-concept” for AAV-neurturin (CERE-120) in Parkinson’s disease. Neurobiol Aging 2013;34:35–61.PubMedCrossRefGoogle Scholar
  10. Bayliss JA, Lemus MB, Stark R, et al. Ghrelin-AMPK Signaling Mediates the Neuroprotective Effects of Calorie Restriction in Parkinson’s Disease. J Neurosci 2016;36:3049–63.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Beavan MS, Schapira AH. Glucocerebrosidase mutations and the pathogenesis of Parkinson disease. Ann Med 2013;45: 511–521.PubMedCrossRefGoogle Scholar
  12. Bose A, Beal MF. Mitochondrial dysfunction in Parkinson’s disease. J Neurochem 2016; 139(Suppl.1):216–31.PubMedCrossRefGoogle Scholar
  13. Bousquet M, Saint-Pierre M, Julien C, et al. Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinson’s disease. FASEB J 2008;22:1213–25.PubMedCrossRefGoogle Scholar
  14. Caudle WM, Richardson JR, Wang MZ, et al. Reduced Vesicular Storage of Dopamine Causes Progressive Nigrostriatal Neurodegeneration. J Neurosci 2007;27:8138–8148.PubMedCrossRefGoogle Scholar
  15. Chan CS, Gertler TS, Surmeier DJ. A molecular basis for the increased vulnerability of substantia nigra dopamine neurons in aging and Parkinson’s disease. Mov Disord 2010;25 Suppl 1:S63–70.PubMedCrossRefGoogle Scholar
  16. Chau KY, Cooper JM, Schapira AH. Pramipexole reduces phosphorylation of α-synuclein at serine-129. J Mol Neurosci 2013;51:573–80.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Chen S, Zhang X, Yang D, et al. D2/D3 receptor agonist ropinirole protects dopaminergic cell line against rotenone-induced apoptosis through inhibition of caspase- and JNK-dependent pathways. FEBS Lett 2008;582:603–10.PubMedCrossRefGoogle Scholar
  18. Chen PC, Vargas MR, Pani AK, et al. Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson’s disease: Critical role for the astrocyte. PNAS 2009;106:2933–8.PubMedCrossRefGoogle Scholar
  19. Chen Y, Xiong M, Dong Y, et al. Chemical control of grafted human PSC-derived neurons in a mouse model of Parkinson’s disease. Cell Stem Cell 2016;18:1–10.CrossRefGoogle Scholar
  20. Chung CY, Koprich JB, Hallett PJ, Isacson O. Functional enhancement and protection of dopaminergic terminals by RAB3B overexpression. PNAS 2009;106:22474–9.PubMedCrossRefGoogle Scholar
  21. Coupland KG, Mellick GD, Silburn PA, et al. DNA methylation of the MAPT gene in Parkinson’s disease cohorts and modulation by vitamin E in vitro. Mov Disord 2014;29:1606–14.PubMedCrossRefGoogle Scholar
  22. Dai Y, Tan X, Wu W, et al. Liver X receptor β protects dopaminergic neurons in a mouse model of Parkinson disease. Proc Natl Acad Sci U S A 2012;109:13112–7.PubMedPubMedCentralCrossRefGoogle Scholar
  23. de la Fuente-Fernández R, Appel-Cresswell S, Doudet DJ, Sossi V. Functional neuroimaging in Parkinson’s disease. Expert Opin Med Diagn 2011;5:109–20.PubMedCrossRefGoogle Scholar
  24. Dranka BP, Gifford A, Ghosh A, et al. Diapocynin prevents early Parkinson’s disease symptoms in the leucine-rich repeat kinase 2 (LRRK2R1441G) transgenic mouse. Neurosci Lett 2013;549:57–62.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Dunn AR, Stout KA, Ozawa M, et al. Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease. Proc Natl Acad Sci U S A 2017;114:E2253-E2262PubMedPubMedCentralCrossRefGoogle Scholar
  26. Emborg ME, Liu Y, Xi J, et al. Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain. Cell Reports 2013;3:646–50.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Evatt ML, Delong MR, Kumari M, et al. High Prevalence of Hypovitaminosis D Status in Patients With Early Parkinson Disease. Arch Neurol 2011;68:314–9.PubMedCrossRefGoogle Scholar
  28. Faherty CJ, Raviie Shepherd K, Herasimtschuk A, et al. Environmental enrichment in adulthood eliminates neuronal death in experimental Parkinsonism. Brain Res Mol Brain Res 2005;134:170–9.PubMedCrossRefGoogle Scholar
  29. Fenoy AJ, Goetz L, Chabardès S, Xia Y. Deep brain stimulation: are astrocytes a key driver behind the scene? CNS Neurosci Ther 2014;20:191–201.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Ferreira DG, Temido-Ferreira M, Miranda HV, et al. α-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B. Nat Neurosci 2017; 20: 1569–79.PubMedCrossRefGoogle Scholar
  31. Fujimaki M, Saiki S, Li Y, et al. Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease. Neurology 2018;90:e404-e411.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Gerson JE, Farmer KM, Henson N, et al. Tau oligomers mediate α-synuclein toxicity and can be targeted by immunotherapy. Mol Neurodegener 2018;13:13.PubMedPubMedCentralCrossRefGoogle Scholar
  33. González-Lizárraga F, Socías SB, Ávila CL, et al. Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species. Sci Rep 2017;7:41755.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Hamamichi S, Rivas RN, Knight AL, et al. Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson’s disease model. PNAS 2008;105:728–733.PubMedCrossRefGoogle Scholar
  35. Hauser RA, Lew MF, Hurtig HI, et al; TEMPO Open-label Study Group. Long-term outcome of early versus delayed rasagiline treatment in early Parkinson’s disease. Mov Disord 2009;24:564–73.Google Scholar
  36. Helmschrodt C, Höbel S, Schöniger S, et al. Polyethylenimine Nanoparticle-Mediated siRNA Delivery to Reduce α-Synuclein Expression in a Model of Parkinson’s Disease. Mol Ther Nucleic Acids 2017;9:57–68.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Henderson EJ, Lord SR, Brodie MA, et al. Rivastigmine for gait stability in patients with Parkinson’s disease (ReSPonD): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol 2016;15:249–58.PubMedCrossRefGoogle Scholar
  38. Holemans T, Sørensen DM, van Veen S, et al. A lipid switch unlocks Parkinson’s disease-associated ATP13A2. Proc Natl Acad Sci U S A 2015;112:9040–5.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Hudson G. The ageing brain, mitochondria and neurodegeneration. In: Reeve AK, Simcox EM, Duchen MR, Turnbull DM (eds). Mitochondrial Dysfunction in Neurodegenerative Disorders. 2nd ed. Springer Int Publishing , New York, 2016;59–80.CrossRefGoogle Scholar
  40. Jain KK. Pramipexole. In, Roos RP (ed) MedLink Neurology. Medlink Publishing Corporation, San Diego, California, 2019a.Google Scholar
  41. Jain KK. Rasagiline. In, Roos RP (ed) MedLink Neurology. Medlink Publishing Corporation, San Diego, California, 2019b.Google Scholar
  42. Jain KK. Ropinirole. In, Roos RP (ed) MedLink Neurology. Medlink Publishing Corporation, San Diego, California, 2019c.Google Scholar
  43. Jain KK. Selegiline. In, Roos RP (ed) MedLink Neurology. Medlink Publishing Corporation, San Diego, California, 2019d.Google Scholar
  44. Jain KK. Cell Therapy: technologies, companies and markets. Jain Pharma Biotech Publications, Basel, 2019e.Google Scholar
  45. Jain KK. Gene Therapy: technologies, companies and markets. Jain PharmaBiotech Publications, Basel, 2019f.Google Scholar
  46. Jain KK. Nitric Oxide Therapeutics. Jain PharmaBiotech Publications, Basel, 2019g.Google Scholar
  47. Kachroo A, Schwarzschild MA. Adenosine A2A receptor gene disruption protects in an α-synuclein model of Parkinson’s disease. Ann Neurol 2012;71:278–82.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Knekt P, Kilkkinen A, Rissanen H, et al. Serum Vitamin D and the Risk of Parkinson Disease. Arch Neurol 2010;67:808–811.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Koob AO, Ubhi K, Paulsson JF, et al. Lovastatin ameliorates alpha-synuclein accumulation and oxidation in transgenic mouse models of alpha-synucleinopathies. Exp Neurol 2010;221:267–74.PubMedCrossRefGoogle Scholar
  50. Lang C, Campbell KR, Ryan BJ, et al. Single-Cell Sequencing of iPSC-Dopamine Neurons Reconstructs Disease Progression and Identifies HDAC4 as a Regulator of Parkinson Cell Phenotypes. Cell Stem Cell 2019;24:93–106.e6.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Lautenschläger J, Stephens AD, Fusco G, et al. C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction. Nat Commun 2018;9:712.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Levine PM, Galesic A, Balana AT, et al. α-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson’s disease. PNAS 2019 Jan 16;  https://doi.org/10.1073/pnas.1808845116 (advance online)CrossRefGoogle Scholar
  53. Lee BD, Shin J-H, VanKampen J, et al. Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson’s disease. Nat Med 2010;16:998–1000.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Lewis TB, Glasgow JN, Harms AS, Standaert DG, Curiel DT. Fiber-modified adenovirus for central nervous system Parkinson’s disease gene therapy. Viruses 2014;6:3293–310.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Liu F, Nguyen JL, Hulleman JD, et al. Mechanisms of DJ-1 neuroprotection in a cellular model of Parkinson’s disease. J Neurochem 2008;105:2435–53.PubMedCrossRefGoogle Scholar
  56. Luk KC, Kehm V, Carroll J, et al. Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice, Science 2012;338:949–53.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Ma J, Shaw VE, Mitrofanis J, et al. Does melatonin help save dopaminergic cells in MPTP-treated mice? Parkinsonism Relat Disord 2009;15:307–14.PubMedCrossRefGoogle Scholar
  58. Mack JM, Schamne MG, Sampaio TB, et al. Melatoninergic System in Parkinson’s Disease: From Neuroprotection to the Management of Motor and Nonmotor Symptoms. Oxid Med Cell Longev 2016;2016:3472032.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Madhavan L, Daley BF, Paumier KL, Collier TJ. Transplantation of subventricular zone neural precursors induces an endogenous precursor cell response in a rat model of Parkinson’s disease. J Comp Neurol 2009;515:102–15.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Mankovska IM, Rosova KV, Gonchar OO, et al. Effect of Capicor on the Parkinson’s disease pathogenic links. Fiziol Zh 2019;64:16–24 [Ukraine].CrossRefGoogle Scholar
  61. Matak P, Matak A, Moustafa S, et al. Disrupted iron homeostasis causes dopaminergic neurodegeneration in mice. Proc Natl Acad Sci U S A 2016;113:3428–35.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Mittal S, Bjørnevik K, Im DS, et al. β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease. Science 2017;357:891–898.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Mittermeyer G, Christine CW, Rosenbluth KH, et al. Long-term evaluation of a phase 1 study of AADC gene therapy for Parkinson’s disease. Hum Gene Ther 2012;23:377–81.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Müller T. New small molecules for the treatment of Parkinson’s disease. Expert Opin Investig Drugs 2010;19:1077–86.PubMedCrossRefGoogle Scholar
  65. Nakata Y, Yasuda T, Mochizuki H. Recent progress in gene therapy for Parkinson’s disease. Curr Mol Med 2012;12:1311–8.PubMedCrossRefGoogle Scholar
  66. Olanow CW, Rascol O, Hauser R, et al. A Double-Blind, Delayed-Start Trial of Rasagiline in Parkinson’s Disease. NEJM 2009; 361:1268–78.PubMedCrossRefGoogle Scholar
  67. Onofrj M, Bonanni L, Thomas A. An expert opinion on safinamide in Parkinson’s disease. Expert Opin Investig Drugs 2008;17:1115–25.PubMedCrossRefGoogle Scholar
  68. Pagan F, Hebron M, Valadez EH, et al. Nilotinib Effects in Parkinson’s disease and Dementia with Lewy bodies. J Parkinsons Dis 2016;6:503–17.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Palfi S, Gurruchaga JM, Ralph GS, et al. Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson’s disease: a dose escalation, open-label, phase 1/2 trial. Lancet 2014;383:1138–46.PubMedCrossRefGoogle Scholar
  70. Paul G, Zachrisson O, Varrone A, et al. Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson’s disease patients. J Clin Invest 2015;125:1339–46.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Paul R, Phukan BC, Justin Thenmozhi A, et al. Melatonin protects against behavioral deficits, dopamine loss and oxidative stress in homocysteine model of Parkinson’s disease. Life Sci 2018;192:238–245.PubMedCrossRefGoogle Scholar
  72. Perni M, Galvagnion C, Maltsev A, et al. A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity. Proc Natl Acad Sci U S A 2017;114:E1009-E1017.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Pineda A, Burré J. Modulating membrane binding of α-synuclein as a therapeutic strategy. Proc Natl Acad Sci U S A 2017;114:1223–1225.PubMedPubMedCentralCrossRefGoogle Scholar
  74. Pinna A. Novel investigational adenosine A2A receptor antagonists for Parkinson’s disease. Expert Opin Investig Drugs 2009;18:1619–31.PubMedCrossRefGoogle Scholar
  75. 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;11:845–60.PubMedCrossRefGoogle Scholar
  76. Rappold PM, Cui M, Grima JC, et al. Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo. Nature Commun 2014; 5:5244.CrossRefGoogle Scholar
  77. Renko JM, Bäck S, Voutilainen MH, et al. Mesencephalic astrocyte-derived neurotrophic factor (MANF) elevates stimulus-evoked release of dopamine in freely-moving rats. Mol Neurobiol 2018;55:6755–68.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Rousseaux MW, Marcogliese PC, Qu D, et al. Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease. Proc Natl Acad Sci U S A 2012;109:15918–23.PubMedPubMedCentralCrossRefGoogle Scholar
  79. Sampaio TB, Savall AS, Gutierrez MEZ, Pinton S. Neurotrophic factors in Alzheimer’s and Parkinson’s diseases: implications for pathogenesis and therapy. Neural Regen Res 2017;12:549–57.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Santaniello S, McCarthy MM, Montgomery EB, et al. Therapeutic mechanisms of high-frequency stimulation in Parkinson’s disease and neural restoration via loop-based reinforcement. Proc Natl Acad Sci U S A 2015;112:E586–95.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Sardi SP, Clark J, Viel C, et al. Augmenting CNS glucocerebrosidase activity as a therapeutic strategy for parkinsonism and other Gaucher-related synucleinopathies. PNAS 2013 110:3537–42.PubMedCrossRefGoogle Scholar
  82. Schapira A. Safinamide in the treatment of Parkinson’s disease. Expert Opin Pharmacother 2010;11:2261–8.PubMedCrossRefGoogle Scholar
  83. Schapira HV, Olanow CW, Greenamyre JT, Bezard E. Slowing of neurodegeneration in Parkinson’s disease and Huntington’s disease: future therapeutic perspectives. The Lancet 2014;384:545–55.CrossRefGoogle Scholar
  84. Spathis AD, Asvos X, Ziavra D, et al.Nurr1:RXRα heterodimer activation as monotherapy for Parkinson’s disease. Proc Natl Acad Sci U S A 2017;114:3999–4004.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Stasi MA, Minetti P, Lombardo K, et al. Animal models of Parkinson′s disease: Effects of two adenosine A2A receptor antagonists ST4206 and ST3932, metabolites of 2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine (ST1535). Eur J Pharmacol 2015;761:353–61.PubMedCrossRefGoogle Scholar
  86. Suzuki M, Yoshioka M, Hashimoto M, et al. Randomized, double-blind, placebo-controlled trial of vitamin D supplement in Parkinson’s disease. Am J Clin Nutr 2013;97:1004–13..PubMedCrossRefGoogle Scholar
  87. Tang T, Li Y, Jiao Q, Du X, Jiang H. Cerebral dopamine neurotrophic factor: a potential therapeutic agent for Parkinson’s disease. Neurosci Bull 2017;33:568–75.PubMedPubMedCentralCrossRefGoogle Scholar
  88. Valles F, Fiandaca MS, Eberling JL, et al. Qualitative imaging of adeno-associated virus serotype 2-human aromatic L-amino acid decarboxylase gene therapy in a phase I study for the treatment of Parkinson disease. Neurosurgery 2010;67:1377–85.PubMedCrossRefGoogle Scholar
  89. Villafane G, Thiriez C, Audureau E, et al. High-dose transdermal nicotine in Parkinson’s disease patients: a randomized, open-label, blinded-endpoint evaluation phase 2 study. Eur J Neurol 2018;25:120–127.PubMedCrossRefGoogle Scholar
  90. Visanji NP, Orsi A, Johnston TH, et al. PYM50028, a novel, orally active, nonpeptide neurotrophic factor inducer, prevents and reverses neuronal damage induced by MPP+ in mesencephalic neurons and by MPTP in a mouse model of Parkinson’s disease. FASEB J 2008;22:2488–97.PubMedCrossRefGoogle Scholar
  91. 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;29:9651–9.PubMedCrossRefGoogle Scholar
  92. West AB. Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson disease. Exp Neurol 2017;298(Pt B):236–245.PubMedPubMedCentralCrossRefGoogle Scholar
  93. Wongprayoon P, Govitrapong P. Melatonin as a mitochondrial protector in neurodegenerative diseases. Cell Mol Life Sci 2017;74:3999–4014.PubMedCrossRefGoogle Scholar
  94. Yue W, Chen Z, Liu H, Yan C, Chen M, Feng D, et al. A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30. Nat Publ Gr 2014; 24:482–96.Google Scholar
  95. Zeng W, Zhang W, Lu F, et al. Resveratrol attenuates MPP+-induced mitochondrial dysfunction and cell apoptosis via AKT/GSK-3β pathway in SN4741 cells. Neurosci Lett 2017;637:50–56.PubMedCrossRefGoogle Scholar

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Authors and Affiliations

  • Kewal K. Jain
    • 1
  1. 1.Jain PharmaBiotechBaselSwitzerland

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