Skip to content
2000
Volume 24, Issue 12
  • ISSN: 1871-5273
  • E-ISSN: 1996-3181

Abstract

The zebrafish (Danio rerio) is widely utilised as a live vertebrate model in research on neurological development and nervous system diseases. This species exhibits various distinctive attributes that render it well-suited for investigating neurological disorders such as Parkinson’s disease (PD). Zebrafish and humans have a genetic similarity of around 70%, and approximately 84% of the genes associated with human diseases have zebrafish equivalents. The genetic similarities and presence of neurotransmitters like dopamine allow scientists to study PD genes and proteins. Zebrafish are often challenged with neurotoxins to induce Parkinsonian symptoms, allowing researchers to evaluate attendant biochemical pathways. Zebrafish can also repair damaged organs, increasing their potential value in PD research. Because of their regenerative capacity and genetic resemblance to humans, these species can be used to study dopamine neurodegeneration and prospective PD treatments. In addition to PD, zebrafish are helpful models for studying Huntington's disease, Alzheimer's disease, epilepsy, depression, schizophrenia, and anxiety disorders. This article emphasizes significant findings of relevance to PD using the zebrafish model, describing its challenges and benefits. The investigation of key genes, protein pathways, and neurotoxins provides the opportunity to facilitate understanding of the role of dopamine neurotransmitters in PD and expedite the development of potentially promising therapeutic strategies.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cnsnddt/10.2174/0118715273367688250528122144
2025-06-11
2025-12-14

  • From This Site

    /content/journals/cnsnddt/10.2174/0118715273367688250528122144
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. DagA. LuciaB. HallidayG.M. Parkinson disease-associated cognitive impairment.Nat. Rev. Dis. Primers2021714710.1038/s41572‑021‑00280‑3
     [Google Scholar]
  2. WangZ. HuB. ZhouW. XuM. WangD. Hopf bifurcation mechanism analysis in an improved cortex-basal ganglia network with distributed delays: An application to Parkinson’s disease.Chaos Solitons Fractals202316611302210.1016/j.chaos.2022.113022
     [Google Scholar]
  3. NoyceA.J. LeesA.J. SchragA.E. The prediagnostic phase of Parkinson’s disease.J. Neurol. Neurosurg. Psychiatry201687887187810.1136/jnnp‑2015‑311890 26848171
     [Google Scholar]
  4. ChiaK. KlingseisenA. SiegerD. PrillerJ. Zebrafish as a model organism for neurodegenerative disease.Front. Mol. Neurosci.20221594048410.3389/fnmol.2022.940484 36311026
     [Google Scholar]
  5. HorzmannK. FreemanJ. Zebrafish get connected: Investigating neurotransmission targets and alterations in chemical toxicity.Toxics2016431910.3390/toxics4030019 28730152
     [Google Scholar]
  6. HuangW. Percie du SertN. VollertJ. General principles of preclinical study design.Good Research Practice in Non-Clinical Pharmacology and Biomedicine Handbook of Experimental Pharmacology.Cham: Springer2020257556910.1007/164_2019_277
     [Google Scholar]
  7. BuddayS. OvaertT.C. HolzapfelG.A. SteinmannP. KuhlE. Fifty shades of brain: A review on the mechanical testing and modeling of brain tissue.Arch. Comput. Methods Eng.20202741187123010.1007/s11831‑019‑09352‑w
     [Google Scholar]
  8. KhanF.R. AlhewairiniS.S. Zebrafish (Danio rerio) as a model organism.Curr Trends Cancer Manag201827318
     [Google Scholar]
  9. JuckerM. The benefits and limitations of animal models for translational research in neurodegenerative diseases.Nat. Med.201016111210121410.1038/nm.2224 21052075
     [Google Scholar]
  10. SégalatL. Invertebrate animal models of diseases as screening tools in drug discovery.ACS Chem. Biol.20072423123610.1021/cb700009m 17455900
     [Google Scholar]
  11. CaramilloEM EchevarriaDJ Alzheimer’s disease in the zebrafish: Where can we take it?Behav Pharmacol2017282 and 31798610.1097/FBP.0000000000000284 28177980
     [Google Scholar]
  12. VijayanathanY. LimF.T. LimS.M. 6-OHDA-lesioned adult zebrafish as a useful Parkinson’s disease model for dopaminergic neuroregeneration.Neurotox. Res.201732349650810.1007/s12640‑017‑9778‑x 28707266
     [Google Scholar]
  13. SidorovaY.A. VolchoK.P. SalakhutdinovN.F. Neuroregeneration in Parkinson’s disease: From proteins to small molecules.Curr. Neuropharmacol.201917326828710.2174/1570159X16666180905094123 30182859
     [Google Scholar]
  14. PitchaiA. RajaretinamR.K. FreemanJ.L. Zebrafish as an emerging model for bioassay-guided natural product drug discovery for neurological disorders.Medicines2019626110.3390/medicines6020061 31151179
     [Google Scholar]
  15. RobeaM.A. BalmusI.M. CiobicaA. Parkinson’s disease-induced zebrafish models: Focussing on oxidative stress implications and sleep processes.Oxid. Med. Cell. Longev.2020202011510.1155/2020/1370837 32908622
     [Google Scholar]
  16. RinkE. WullimannM.F. Connections of the ventral telencephalon (subpallium) in the zebrafish (Danio rerio).Brain Res.20041011220622010.1016/j.brainres.2004.03.027 15157807
     [Google Scholar]
  17. MissaleC. NashS.R. RobinsonS.W. JaberM. CaronM.G. Dopamine receptors: From structure to function.Physiol. Rev.199878118922510.1152/physrev.1998.78.1.189 9457173
     [Google Scholar]
  18. MurrayR.M. LappinJ. Di FortiM. Schizophrenia: From developmental deviance to dopamine dysregulation.Eur. Neuropsychopharmacol.200818S129S13410.1016/j.euroneuro.2008.04.002 18499406
     [Google Scholar]
  19. SchultzW. Getting formal with dopamine and reward.Neuron200236224126310.1016/S0896‑6273(02)00967‑4 12383780
     [Google Scholar]
  20. RinkE. WullimannM.F. Development of the catecholaminergic system in the early zebrafish brain: An immunohistochemical study.Brain Res. Dev. Brain Res.200213718910010.1016/S0165‑3806(02)00354‑1 12128258
     [Google Scholar]
  21. CallierS. SnapyanM. Le CromS. ProuD. VincentJ.D. VernierP. Evolution and cell biology of dopamine receptors in vertebrates.Biol. Cell200395748950210.1016/S0248‑4900(03)00089‑3 14597267
     [Google Scholar]
  22. XiY. NobleS. EkkerM. Modeling neurodegeneration in zebrafish.Curr. Neurol. Neurosci. Rep.201111327428210.1007/s11910‑011‑0182‑2 21271309
     [Google Scholar]
  23. WaselO. FreemanJ.L. Chemical and genetic zebrafish models to define mechanisms of and treatments for dopaminergic neurodegeneration.Int. J. Mol. Sci.20202117598110.3390/ijms21175981 32825242
     [Google Scholar]
  24. BenarrochE.E. Monoamine transporters.Neurology201381876176810.1212/WNL.0b013e3182a1ab4a 23902707
     [Google Scholar]
  25. SemenovaS. RozovS. PanulaP. Distribution, properties, and inhibitor sensitivity of zebrafish catechol-O-methyl transferases (COMT).Biochem. Pharmacol.201714514715710.1016/j.bcp.2017.08.017 28844929
     [Google Scholar]
  26. DoyleJ.M. CrollR.P. A critical review of zebrafish models of Parkinson’s disease.Front. Pharmacol.20221383582710.3389/fphar.2022.835827 35370740
     [Google Scholar]
  27. WenL. WeiW. GuW. Visualization of monoaminergic neurons and neurotoxicity of MPTP in live transgenic zebrafish.Dev. Biol.20083141849210.1016/j.ydbio.2007.11.012 18164283
     [Google Scholar]
  28. DukesA.A. BaiQ. Van LaarV.S. Live imaging of mitochondrial dynamics in CNS dopaminergic neurons in vivo demonstrates early reversal of mitochondrial transport following MPP+ exposure.Neurobiol. Dis.20169523824910.1016/j.nbd.2016.07.020 27452482
     [Google Scholar]
  29. AnichtchikO.V. KaslinJ. PeitsaroN. ScheininM. PanulaP. Neurochemical and behavioural changes in zebrafish Danio rerio after systemic administration of 6‐hydroxydopamine and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine.J. Neurochem.200488244345310.1111/j.1471‑4159.2004.02190.x 14690532
     [Google Scholar]
  30. Sarath BabuN. MurthyC.L.N. KakaraS. SharmaR. Brahmendra SwamyC.V. IdrisM.M. 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydro-pyridine induced Parkinson’s disease in zebrafish.Proteomics20161691407142010.1002/pmic.201500291 26959078
     [Google Scholar]
  31. SallinenV. TorkkoV. SundvikM. MPTP and MPP+ target specific aminergic cell populations in larval zebrafish.J. Neurochem.2009108371973110.1111/j.1471‑4159.2008.05793.x 19046410
     [Google Scholar]
  32. ParngC. RoyN.M. TonC. LinY. McGrathP. Neurotoxicity assessment using zebrafish.J. Pharmacol. Toxicol. Methods200755110311210.1016/j.vascn.2006.04.004 16769228
     [Google Scholar]
  33. FengC.W. WenZ.H. HuangS.Y. Effects of 6-hydroxydopamine exposure on motor activity and biochemical expression in zebrafish (Danio rerio) larvae.Zebrafish201411322723910.1089/zeb.2013.0950 24720843
     [Google Scholar]
  34. BretaudS. LeeS. GuoS. Sensitivity of zebrafish to environmental toxins implicated in Parkinson’s disease.Neurotoxicol. Teratol.200426685786410.1016/j.ntt.2004.06.014 15451049
     [Google Scholar]
  35. WangL. ShengW. TanZ. Treatment of Parkinson’s disease in Zebrafish model with a berberine derivative capable of crossing blood brain barrier, targeting mitochondria, and convenient for bioimaging experiments.Comp. Biochem. Physiol. C Toxicol. Pharmacol.202124910915110.1016/j.cbpc.2021.109151 34343700
     [Google Scholar]
  36. Nellore J,P.N. Paraquat exposure induces behavioral deficits in larval zebrafish during the window of dopamine neurogenesis.Toxicol. Rep.2015295095610.1016/j.toxrep.2015.06.007 28962434
     [Google Scholar]
  37. WangQ. LiuS. HuD. Identification of apoptosis and macrophage migration events in paraquat-induced oxidative stress using a zebrafish model.Life Sci.201615711612410.1016/j.lfs.2016.06.009 27288846
     [Google Scholar]
  38. WangX.H. SoudersC.L. ZhaoY.H. MartyniukC.J. Paraquat affects mitochondrial bioenergetics, dopamine system expression, and locomotor activity in zebrafish (Danio rerio).Chemosphere201819110611710.1016/j.chemosphere.2017.10.032 29031050
     [Google Scholar]
  39. NunesM.E. MüllerT.E. BragaM.M. Chronic treatment with paraquat induces brain injury, changes in antioxidant defenses system, and modulates behavioral functions in zebrafish.Mol. Neurobiol.20175463925393410.1007/s12035‑016‑9919‑x 27229491
     [Google Scholar]
  40. KalynM. HuaK. Mohd NoorS. WongC.E.D. EkkerM. Comprehensive analysis of neurotoxin-induced ablation of dopaminergic neurons in zebrafish larvae.Biomedicines201981110.3390/biomedicines8010001 31905670
     [Google Scholar]
  41. RazaliK. OthmanN. Mohd NasirM.H. The promise of the zebrafish model for Parkinson’s disease: Today’s science and tomorrow’s treatment.Front. Genet.20211265555010.3389/fgene.2021.655550 33936174
     [Google Scholar]
  42. SulzerD. Multiple hit hypotheses for dopamine neuron loss in Parkinson’s disease.Trends Neurosci.200730524425010.1016/j.tins.2007.03.009 17418429
     [Google Scholar]
  43. DeMaagdG PhilipA Parkinson’s disease and its management: Part 1: Disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis.201540850432 26236139
     [Google Scholar]
  44. BlauwendraatC. NallsM.A. SingletonA.B. The genetic architecture of Parkinson’s disease.Lancet Neurol.202019217017810.1016/S1474‑4422(19)30287‑X 31521533
     [Google Scholar]
  45. PolymeropoulosM.H. HigginsJ.J. GolbeL.I. Mapping of a gene for Parkinson’s disease to chromosome 4q21-q23.Science199627452901197119910.1126/science.274.5290.1197 8895469
     [Google Scholar]
  46. NuytemansK. TheunsJ. CrutsM. Van BroeckhovenC. Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: A mutation update.Hum. Mutat.201031776378010.1002/humu.21277 20506312
     [Google Scholar]
  47. MarquesO. OuteiroT.F. Alpha-synuclein: from secretion to dysfunction and death.Cell Death Dis.201237e350e010.1038/cddis.2012.94 22825468
     [Google Scholar]
  48. Barré-SinoussiF. MontagutelliX. Animal models are essential to biological research: Issues and perspectives.Future Sci. OA201514FSO6310.4155/fso.15.63
     [Google Scholar]
  49. DavidsonW.S. JonasA. ClaytonD.F. GeorgeJ.M. Stabilization of α-synuclein secondary structure upon binding to synthetic membranes.J. Biol. Chem.1998273169443944910.1074/jbc.273.16.9443 9545270
     [Google Scholar]
  50. Mahul-MellierA.L. BurtscherJ. MaharjanN. The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration.Proc. Natl. Acad. Sci. USA202011794971498210.1073/pnas.1913904117 32075919
     [Google Scholar]
  51. ToniM. CioniC. Fish synucleins: An update.Mar. Drugs201513116665668610.3390/md13116665 26528989
     [Google Scholar]
  52. ChandraS. FornaiF. KwonH.B. Double-knockout mice for α- and β-synucleins: Effect on synaptic functions.Proc. Natl. Acad. Sci. USA200410141149661497110.1073/pnas.0406283101 15465911
     [Google Scholar]
  53. ZhangJ. LiX. LiJ.D. The roles of post-translational modifications on α-synuclein in the pathogenesis of Parkinson’s diseases.Front. Neurosci.20191338110.3389/fnins.2019.00381 31057362
     [Google Scholar]
  54. KitadaT. AsakawaS. HattoriN. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.Nature1998392667660560810.1038/33416 9560156
     [Google Scholar]
  55. ImaiY. SodaM. TakahashiR. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity.J. Biol. Chem.200027546356613566410.1074/jbc.C000447200 10973942
     [Google Scholar]
  56. JęśkoH. LenkiewiczA.M. WilkaniecA. AdamczykA. The interplay between parkin and alpha-synuclein; possible implications for the pathogenesis of Parkinson’s disease.Acta Neurobiol. Exp.201979327729010.21307/ane‑2019‑026 31587020
     [Google Scholar]
  57. SequeiraS. α-Synuclein degradation by parkin is impaired in Parkinson’s disease.Trends Neurosci.2001241056910.1016/S0166‑2236(00)02022‑1
     [Google Scholar]
  58. WilkaniecA. LenkiewiczA.M. BabiecL. Exogenous alpha-synuclein evoked parkin downregulation promotes mitochondrial dysfunction in neuronal cells. implications for Parkinson’s disease pathology.Front. Aging Neurosci.20211359147510.3389/fnagi.2021.591475 33716707
     [Google Scholar]
  59. ChungK.K.K. ZhangY. LimK.L. Parkin ubiquitinates the α-synuclein-interacting protein, synphilin-1: Implications for Lewy-body formation in Parkinson disease.Nat. Med.20017101144115010.1038/nm1001‑1144 11590439
     [Google Scholar]
  60. SelvarajS. PiramanayagamS. Impact of gene mutation in the development of Parkinson’s disease.Genes Dis.20196212012810.1016/j.gendis.2019.01.004 31193965
     [Google Scholar]
  61. BarnhillL.M. MurataH. BronsteinJ.M. Studying the pathophysiology of Parkinson’s disease using zebrafish.Biomedicines20208719710.3390/biomedicines8070197 32645821
     [Google Scholar]
  62. AshrafiG. SchwarzT.L. The pathways of mitophagy for quality control and clearance of mitochondria.Cell Death Differ.2013201314210.1038/cdd.2012.81 22743996
     [Google Scholar]
  63. KhandelwalP. MoussaC.E.H. The relationship between parkin and protein aggregation in neurodegenerative diseases.Front. Psychiatry201011510.3389/fpsyt.2010.00015 21423426
     [Google Scholar]
  64. GeP. DawsonV.L. DawsonT.M. PINK1 and Parkin mitochondrial quality control: A source of regional vulnerability in Parkinson’s disease.Mol. Neurodegener.20201512010.1186/s13024‑020‑00367‑7 32169097
     [Google Scholar]
  65. ValenteE.M. BentivoglioA.R. DixonP.H. Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36.Am. J. Hum. Genet.200168489590010.1086/319522 11254447
     [Google Scholar]
  66. ValenteE.M. Abou-SleimanP.M. CaputoV. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1.Science200430456741158116010.1126/science.1096284 15087508
     [Google Scholar]
  67. WangX. SchwarzT.L. The mechanism of Ca2+-dependent regulation of kinesin-mediated mitochondrial motility.Cell2009136116317410.1016/j.cell.2008.11.046 19135897
     [Google Scholar]
  68. WeihofenA. ThomasK.J. OstaszewskiB.L. CooksonM.R. SelkoeD.J. Pink1 forms a multiprotein complex with Miro and Milton, linking Pink1 function to mitochondrial trafficking.Biochemistry20094892045205210.1021/bi8019178 19152501
     [Google Scholar]
  69. GandhiS. Wood-KaczmarA. YaoZ. PINK1-associated Parkinson’s disease is caused by neuronal vulnerability to calcium-induced cell death.Mol. Cell200933562763810.1016/j.molcel.2009.02.013 19285945
     [Google Scholar]
  70. DengH. DodsonM.W. HuangH. GuoM. The Parkinson’s disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila.Proc. Natl. Acad. Sci. USA200810538145031450810.1073/pnas.0803998105 18799731
     [Google Scholar]
  71. GandhiS. Plun-FavreauH. Mutations and mechanism: How PINK1 may contribute to risk of sporadic Parkinson’s disease.Brain201714012510.1093/brain/aww320 28031215
     [Google Scholar]
  72. BastideM.F. BidoS. DuteilN. BézardE. Striatal NELF-mediated RNA polymerase II stalling controls l -dopa induced dyskinesia.Neurobiol. Dis.201685939810.1016/j.nbd.2015.10.013 26480869
     [Google Scholar]
  73. PriyadarshiniM. OroscoL.A. PanulaP.J. Oxidative stress and regulation of Pink1 in zebrafish (Danio rerio).PLoS One2013811e8185110.1371/journal.pone.0081851 24324558
     [Google Scholar]
  74. XiY. RyanJ. NobleS. YuM. YilbasA.E. EkkerM. Impaired dopaminergic neuron development and locomotor function in zebrafish with loss of pink1 function.Eur. J. Neurosci.201031462363310.1111/j.1460‑9568.2010.07091.x 20141529
     [Google Scholar]
  75. AnichtchikO. DiekmannH. FlemingA. RoachA. GoldsmithP. RubinszteinD.C. Loss of PINK1 function affects development and results in neurodegeneration in zebrafish.J. Neurosci.200828338199820710.1523/JNEUROSCI.0979‑08.2008 18701682
     [Google Scholar]
  76. McQuibbanG.A. BulmanD.E. The PARLance of Parkinson disease.Autophagy20117779079210.4161/auto.7.7.15614 21471738
     [Google Scholar]
  77. LiuJ. LiuW. LiR. YangH. Mitophagy in Parkinson’s disease: From pathogenesis to treatment.Cells20198771210.3390/cells8070712 31336937
     [Google Scholar]
  78. NobleS. IsmailA. GodoyR. XiY. EkkerM. Zebrafish Parla‐ and Parlb‐deficiency affects dopaminergic neuron patterning and embryonic survival.J. Neurochem.2012122119620710.1111/j.1471‑4159.2012.07758.x 22506991
     [Google Scholar]
  79. ShamchukA.L. AllisonW.T. TierneyK.B. The importance of olfactory and motor endpoints for zebrafish models of neurodegenerative disease.Animal models for the study of human disease.Elsevier201752555410.1016/B978‑0‑12‑809468‑6.00021‑8
     [Google Scholar]
  80. MerhiR. KalynM. Zhu-PawlowskyA. EkkerM. Loss of parla function results in inactivity, olfactory impairment, and dopamine neuron loss in zebrafish.Biomedicines20219220510.3390/biomedicines9020205 33670667
     [Google Scholar]
  81. BonifatiV. RizzuP. van BarenM.J. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.Science2003299560425625910.1126/science.1077209 12446870
     [Google Scholar]
  82. LevN. IckowiczD. BarhumY. LevS. MelamedE. OffenD. DJ-1 protects against dopamine toxicity.J. Neural Transm.2009116215116010.1007/s00702‑008‑0134‑4 18974921
     [Google Scholar]
  83. XiongH. WangD. ChenL. Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation.J. Clin. Invest.2009119365066010.1172/JCI37617 19229105
     [Google Scholar]
  84. BandyopadhyayS. CooksonM.R. Evolutionary and functional relationships within the DJ1 superfamily.BMC Evol. Biol.200441610.1186/1471‑2148‑4‑6 15070401
     [Google Scholar]
  85. BuneevaO.A. MedvedevA.E. DJ-1 protein and its role in the development of Parkinson’s disease: Studies on experimental models.Biochemistry202186662764010.1134/S000629792106002X 34225587
     [Google Scholar]
  86. BretaudS. AllenC. InghamP.W. BandmannO. p53‐dependent neuronal cell death in a DJ‐1‐deficient zebrafish model of Parkinson’s disease.J. Neurochem.200710061626163510.1111/j.1471‑4159.2006.04291.x 17166173
     [Google Scholar]
  87. KatoI. MaitaH. Takahashi-NikiK. Oxidized DJ-1 inhibits p53 by sequestering p53 from promoters in a DNA-binding affinity-dependent manner.Mol. Cell. Biol.201333234035910.1128/MCB.01350‑12 23149933
     [Google Scholar]
  88. RepiciM. GiorginiF. DJ-1 in Parkinson’s disease: Clinical insights and therapeutic perspectives.J. Clin. Med.201989137710.3390/jcm8091377 31484320
     [Google Scholar]
  89. EdsonA.J. HushagenH.A. FrøysetA.K. Dysregulation in the brain protein profile of zebrafish lacking the Parkinson’s disease-related protein DJ-1.Mol. Neurobiol.201956128306832210.1007/s12035‑019‑01667‑w 31218647
     [Google Scholar]
  90. FunayamaM. HasegawaK. KowaH. SaitoM. TsujiS. ObataF. A new locus for Parkinson’s disease (PARK8) maps to chromosome 12p11.2-q13.1.Ann. Neurol.200251329630110.1002/ana.10113 11891824
     [Google Scholar]
  91. Paisán-RuízC. JainS. EvansE.W. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease.Neuron200444459560010.1016/j.neuron.2004.10.023 15541308
     [Google Scholar]
  92. PrabhudesaiS. BensabeurF.Z. AbdullahR. LRRK2 knockdown in zebrafish causes developmental defects, neuronal loss, and synuclein aggregation.J. Neurosci. Res.201694871773510.1002/jnr.23754 27265751
     [Google Scholar]
  93. RuiQ. NiH. LiD. GaoR. ChenG. The role of LRRK2 in neurodegeneration of Parkinson disease.Curr. Neuropharmacol.20181691348135710.2174/1570159X16666180222165418 29473513
     [Google Scholar]
  94. TsikaE. MooreD.J. Mechanisms of LRRK2-mediated neurodegeneration.Curr. Neurol. Neurosci. Rep.201212325126010.1007/s11910‑012‑0265‑8 22441981
     [Google Scholar]
  95. MartinI. KimJ.W. DawsonV.L. DawsonT.M. LRRK2 pathobiology in Parkinson’s disease.J. Neurochem.2014131555456510.1111/jnc.12949 25251388
     [Google Scholar]
  96. ShengD. QuD. KwokK.H.H. Deletion of the WD40 domain of LRRK2 in Zebrafish causes Parkinsonism-like loss of neurons and locomotive defect.PLoS Genet.201064e100091410.1371/journal.pgen.1000914 20421934
     [Google Scholar]
  97. ShengD. SeeK. HuX. Disruption of LRRK2 in Zebrafish leads to hyperactivity and weakened antibacterial response.Biochem. Biophys. Res. Commun.201849741104110910.1016/j.bbrc.2018.02.186 29499195
     [Google Scholar]
  98. MilaneseC. SagerJ.J. BaiQ. Hypokinesia and reduced dopamine levels in zebrafish lacking β- and γ1-synucleins.J. Biol. Chem.201228752971298310.1074/jbc.M111.308312 22128150
     [Google Scholar]
  99. LullaA. BarnhillL. BitanG. Neurotoxicity of the Parkinson disease-associated pesticide ziram is synuclein-dependent in zebrafish embryos.Environ. Health Perspect.2016124111766177510.1289/EHP141 27301718
     [Google Scholar]
  100. FlinnL. MortiboysH. VolkmannK. KösterR.W. InghamP.W. BandmannO. Complex I deficiency and dopaminergic neuronal cell loss in parkin-deficient zebrafish (Danio rerio).Brain200913261613162310.1093/brain/awp108 19439422
     [Google Scholar]
  101. FlinnL.J. KeatingeM. BretaudS. TigarB causes mitochondrial dysfunction and neuronal loss in PINK1 deficiency.Ann. Neurol.201374683784710.1002/ana.23999 24027110
     [Google Scholar]
  102. RenG. XinS. LiS. ZhongH. LinS. Disruption of LRRK2 does not cause specific loss of dopaminergic neurons in zebrafish.PLoS One201166e2063010.1371/journal.pone.0020630 21698186
     [Google Scholar]
  103. YangT. ShenJ. LemereC.A. Increased DJ-1 expression under oxidative stress and in Alzheimer’s disease brains.Mol. Neurodegener.200941210.1186/1750‑1326‑4‑12
     [Google Scholar]
  104. DumitrescuE. DeshpandeA. WallaceK.N. AndreescuS. Time-dependent monitoring of dopamine in the brain of live embryonic zebrafish using electrochemically pretreated carbon fiber microelectrodes.ACS Measurement Science Au20222326127010.1021/acsmeasuresciau.1c00051 36785866
     [Google Scholar]
  105. KhaliliA. WijngaardenE. ZoidlG.R. RezaiP. Dopaminergic signaling regulates zebrafish larvae’s response to electricity.Biotechnol. J.2022176210056110.1002/biot.202100561 35332995
     [Google Scholar]
  106. WilsonC.N. MustafaS.J. Adenosine receptors in health and disease.Springer200910.1007/978‑3‑540‑89615‑9
     [Google Scholar]
  107. OlanowC.W. BrundinP. Parkinson’s disease and alpha synuclein: Is Parkinson’s disease a prion-like disorder?Mov. Disord.2013281314010.1002/mds.25373 23390095
     [Google Scholar]
  108. Martínez-JauandM. SitgesC. RodríguezV. Pain sensitivity in fibromyalgia is associated with catechol‐ O ‐methyltransferase (COMT) gene.Eur. J. Pain2013171162710.1002/j.1532‑2149.2012.00153.x 22528689
     [Google Scholar]
  109. ZhengJ. ZhangX. ZhenX. Development of adenosine A2A receptor antagonists for the treatment of Parkinson’s disease: A recent update and challenge.ACS Chem. Neurosci.201910278379110.1021/acschemneuro.8b00313 30199223
     [Google Scholar]
  110. Borroto-EscuelaD.O. FuxeK. Adenosine heteroreceptor complexes in the basal ganglia are implicated in Parkinson’s disease and its treatment.J. Neural Transm.2019126445547110.1007/s00702‑019‑01969‑2 30637481
     [Google Scholar]
  111. WangZ. HuB. ZhuL. LinJ. XuM. WangD. The possible mechanism of direct feedback projections from basal ganglia to cortex in beta oscillations of Parkinson’s disease: A theoretical evidence in the competing resonance model.Commun. Nonlinear Sci. Numer. Simul.202312010714210.1016/j.cnsns.2023.107142
     [Google Scholar]
  112. WagganI. RissanenE. TuiskuJ. Effect of dopaminergic medication on adenosine 2A receptor availability in patients with Parkinson’s disease.Parkinsonism Relat. Disord.202186404410.1016/j.parkreldis.2021.03.030 33831661
     [Google Scholar]
  113. WichmannT. Changing views of the pathophysiology of Parkinsonism.Mov. Disord.20193481130114310.1002/mds.27741 31216379
     [Google Scholar]
  114. KulisevskyJ. PoyurovskyM. Adenosine A2A-receptor antagonism and pathophysiology of Parkinson’s disease and drug-induced movement disorders.Eur. Neurol.201267141110.1159/000331768 22134373
     [Google Scholar]
  115. FredholmB.B. SvenningssonP. Why target brain adenosine receptors? A historical perspective.Parkinsonism Relat. Disord.202080S3S610.1016/j.parkreldis.2020.09.027 33349578
     [Google Scholar]
  116. IkramM. ParkT.J. AliT. KimM.O. Antioxidant and neuroprotective effects of caffeine against Alzheimer’s and Parkinson’s disease: Insight into the role of Nrf-2 and A2AR signaling.Antioxidants20209990210.3390/antiox9090902 32971922
     [Google Scholar]
  117. DrakeJ. KanskiJ. VaradarajanS. TsorasM. ButterfieldD.A. Elevation of brain glutathione by γ‐glutamylcysteine ethyl ester protects against peroxynitrite‐induced oxidative stress.J. Neurosci. Res.200268677678410.1002/jnr.10266 12111838
     [Google Scholar]
  118. JankovicJ. TanE.K. Parkinson’s disease: Etiopathogenesis and treatment.J. Neurol. Neurosurg. Psychiatry202091879580810.1136/jnnp‑2019‑322338 32576618
     [Google Scholar]
  119. CalabreseV. CorneliusC. Dinkova-KostovaA.T. CalabreseE.J. MattsonM.P. Cellular stress responses, the hormesis paradigm, and vitagenes: Novel targets for therapeutic intervention in neurodegenerative disorders.Antioxid. Redox Signal.201013111763181110.1089/ars.2009.3074 20446769
     [Google Scholar]
  120. WakabayashiK. Where and how alpha‐synuclein pathology spreads in Parkinson’s disease.Neuropathology202040541542510.1111/neup.12691 32750743
     [Google Scholar]
  121. RekhaK.R. SelvakumarG.P. SanthaK. Inmozhi SivakamasundariR. Geraniol attenuates α-synuclein expression and neuromuscular impairment through increase dopamine content in MPTP intoxicated mice by dose dependent manner.Biochem. Biophys. Res. Commun.2013440466467010.1016/j.bbrc.2013.09.122 24103762
     [Google Scholar]
  122. RochaEM De MirandaB SandersLH Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson’s disease.Neurobiol Dis2018109Pt B2495710.1016/j.nbd.2017.04.004 28400134
     [Google Scholar]
  123. MehraS. SahayS. MajiS.K. α-Synuclein misfolding and aggregation: Implications in Parkinson’s disease pathogenesis.Biochim. Biophys. Acta. Proteins Proteomics201918671089090810.1016/j.bbapap.2019.03.001 30853581
     [Google Scholar]
  124. BrundinP DaveKD KordowerJH Therapeutic approaches to target alpha-synuclein pathology.Exp Neurol2017298Pt B2253510.1016/j.expneurol.2017.10.003 28987463
     [Google Scholar]
  125. KatsaitiI. NixonJ. Are there benefits in adding catechol-O methyltransferase inhibitors in the pharmacotherapy of Parkinson’s disease patients? A systematic review.J. Parkinsons Dis.20188221723110.3233/JPD‑171225 29614697
     [Google Scholar]
  126. PalmaP.N. KissL.E. Soares-da-SilvaP. Catechol-Omethyltransferase inhibitors: Present problems and relevance of the new ones.Emerging drugs and targets for Parkinson’s disease.RSC Publishing2013348310910.13140/2.1.1292.3848
     [Google Scholar]
  127. CacabelosR. Parkinson’s disease: From pathogenesis to pharmacogenomics.Int. J. Mol. Sci.201718355110.3390/ijms18030551 28273839
     [Google Scholar]
  128. de BeerJ. PetzerJ.P. LourensA.C.U. PetzerA. Design, synthesis and evaluation of 3-hydroxypyridin-4-ones as inhibitors of catechol-O-methyltransferase.Mol. Divers.202125275376210.1007/s11030‑020‑10053‑x 32108308
     [Google Scholar]
  129. dos Santos PassosC. SoldiT.C. Torres AbibR. Monoamine oxidase inhibition by monoterpene indole alkaloids and fractions obtained from Psychotria suterella and Psychotria laciniata.J. Enzyme Inhib. Med. Chem.201328361161810.3109/14756366.2012.666536 22424181
     [Google Scholar]
  130. ChamoliM. ChintaS.J. AndersenJ.K. An inducible MAO-B mouse model of Parkinson’s disease: A tool towards better understanding basic disease mechanisms and developing novel therapeutics.J. Neural Transm.2018125111651165810.1007/s00702‑018‑1887‑z 29713806
     [Google Scholar]
  131. DezsiL. VecseiL. Monoamine oxidase B inhibitors in Parkinson’s disease.CNS Neurol. Disord. Drug Targets201716425439
     [Google Scholar]
  132. BindaC. HubálekF. LiM. Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class.J. Med. Chem.20044771767177410.1021/jm031087c 15027868
     [Google Scholar]
  133. SampaioT.F. dos SantosE.U.D. de LimaG.D.C. MAO‐B and COMT genetic variations associated with levodopa treatment response in patients with Parkinson’s disease.J. Clin. Pharmacol.201858792092610.1002/jcph.1096 29578580
     [Google Scholar]
  134. YangJ. SongS. LiJ. LiangT. Neuroprotective effect of curcumin on hippocampal injury in 6-OHDA-induced Parkinson’s disease rat.Pathol. Res. Pract.2014210635736210.1016/j.prp.2014.02.005 24642369
     [Google Scholar]
  135. YangL. WangH. LiuL. XieA. The role of insulin/IGF-1/PI3K/Akt/GSK3β signaling in Parkinson’s disease dementia.Front. Neurosci.2018127310.3389/fnins.2018.00073 29515352
     [Google Scholar]
  136. BajT. SethR. Role of curcumin in regulation of TNF-α mediated brain inflammatory responses.Recent Pat. Inflamm. Allergy Drug Discov.2018121697710.2174/1872213X12666180703163824 29972106
     [Google Scholar]
  137. HuangN. ZhangY. ChenM. Resveratrol delays 6-hydroxydopamine-induced apoptosis by activating the PI3K/Akt signaling pathway.Exp. Gerontol.201912411065310.1016/j.exger.2019.110653 31295526
     [Google Scholar]
  138. DengH. MaZ. Protective effects of berberine against MPTP-induced dopaminergic neuron injury through promoting autophagy in mice.Food Funct.202112188366837510.1039/D1FO01360B 34342315
     [Google Scholar]
  139. HuangS. LiuH. LinY. Berberine protects against NLRP3 inflammasome via ameliorating autophagic impairment in MPTP-induced Parkinson’s disease model.Front. Pharmacol.20211161878710.3389/fphar.2020.618787 33584302
     [Google Scholar]
  140. LiX.M. ZhangX.J. DongM.X. Isorhynchophylline attenuates MPP+-induced apoptosis through endoplasmic reticulum stress-and mitochondria-dependent pathways in PC12 cells: Involvement of antioxidant activity.Neuromolecular Med.201719448049210.1007/s12017‑017‑8462‑x 28822073
     [Google Scholar]
  141. KimS.M. ChungM.J. HaT.J. Neuroprotective effects of black soybean anthocyanins via inactivation of ASK1–JNK/p38 pathways and mobilization of cellular sialic acids.Life Sci.20129021-2287488210.1016/j.lfs.2012.04.025 22575822
     [Google Scholar]
  142. LiX. ZhangJ. ZhangX. DongM. Puerarin suppresses MPP+/MPTP-induced oxidative stress through an Nrf2-dependent mechanism.Food Chem. Toxicol.202014411164410.1016/j.fct.2020.111644 32763437
     [Google Scholar]
  143. ZhaoY. ZhaoJ. ZhangX. Botanical drug puerarin promotes neuronal survival and neurite outgrowth against MPTP/MPP+-induced toxicity via progesterone receptor signaling.Oxid. Med. Cell. Longev.2020202011110.1155/2020/7635291 33123315
     [Google Scholar]
  144. ZhaoX. KongD. ZhouQ. Baicalein alleviates depression-like behavior in rotenone-induced Parkinson’s disease model in mice through activating the BDNF/TrkB/CREB pathway.Biomed. Pharmacother.202114011155610.1016/j.biopha.2021.111556 34087694
     [Google Scholar]
  145. SongJ.X. ChoiM.Y.M. WongK.C.K. Baicalein antagonizes rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to Parkinsonism.Chin. Med.2012711910.1186/1749‑8546‑7‑1 22264378
     [Google Scholar]
  146. ZhengZ.V. CheungC.Y. LyuH. Baicalein enhances the effect of low dose Levodopa on the gait deficits and protects dopaminergic neurons in experimental Parkinsonism.J. Clin. Neurosci.20196424225110.1016/j.jocn.2019.02.005 30905662
     [Google Scholar]
  147. ZhangC. ZhaoM. WangB. The Nrf2-NLRP3-caspase-1 axis mediates the neuroprotective effects of Celastrol in Parkinson’s disease.Redox Biol.20214710213410.1016/j.redox.2021.102134 34600334
     [Google Scholar]
  148. LinM.W. LinC.C. ChenY.H. YangH.B. HungS.Y. Celastrol inhibits dopaminergic neuronal death of Parkinson’s disease through activating mitophagy.Antioxidants2019913710.3390/antiox9010037 31906147
     [Google Scholar]
  149. FengY. ZhengC. ZhangY. Triptolide inhibits preformed fibril‐induced microglial activation by targeting the MicroRNA155‐5p/SHIP1 pathway.Oxid. Med. Cell. Longev.2019201911310.1155/2019/6527638 31182996
     [Google Scholar]
  150. LuS. LiaoQ.S. TangL. MiR-155 affects osteosarcoma cell proliferation and invasion through regulating NF-κB signaling pathway.Eur. Rev. Med. Pharmacol. Sci.2018222276337639 30536304
     [Google Scholar]
  151. HuangY.Y. ZhangQ. ZhangJ.N. Triptolide up-regulates metabotropic glutamate receptor 5 to inhibit microglia activation in the lipopolysaccharide-induced model of Parkinson’s disease.Brain Behav. Immun.2018719310710.1016/j.bbi.2018.04.006 29649522
     [Google Scholar]
  152. HuG. GongX. WangL. Triptolide promotes the clearance of α-synuclein by enhancing autophagy in neuronal cells.Mol. Neurobiol.20175432361237210.1007/s12035‑016‑9808‑3 26957304
     [Google Scholar]
  153. OmarN.A. KumarJ. TeohS.L. Parkinson’s disease model in zebrafish using intraperitoneal MPTP injection.Front. Neurosci.202317123604910.3389/fnins.2023.1236049 37694115
     [Google Scholar]
  154. GaoX. ZhangB. ZhengY. Neuroprotective effect of chlorogenic acid on Parkinson’s disease like symptoms through boosting the autophagy in zebrafish.Eur. J. Pharmacol.202395617595010.1016/j.ejphar.2023.175950 37544423
     [Google Scholar]
  155. SantoG.D. de VerasB.O. RicoE. Hexane extract from SpoSndias mombin L. (Anacardiaceae) prevents behavioral and oxidative status changes on model of Parkinson’s disease in zebrafish.Comp. Biochem. Physiol. C Toxicol. Pharmacol.202124110895310.1016/j.cbpc.2020.108953 33310063
     [Google Scholar]
  156. RenQ. JiangX. ZhangS. Neuroprotective effect of YIAEDAER peptide against Parkinson’s disease like pathology in zebrafish.Biomed. Pharmacother.202214711262910.1016/j.biopha.2022.112629 35030435
     [Google Scholar]
  157. WangM. YeH. JiangP. The alleviative effect of Calendula officinalis L. extract against Parkinson’s disease-like pathology in zebrafish via the involvement of autophagy activation.Front. Neurosci.202317115388910.3389/fnins.2023.1153889 37179558
     [Google Scholar]
  158. GondokesumoM.E. BudipramanaK. PutriP.D.A. NopitasariN.P.D. AdityaM. YusanL.Y. Keluwih (Artocarpus camansi) extract effects in zebrafish models of Parkinson’s disease.Jurnal Teknologi Laboratorium2023121142210.29238/teknolabjournal.v12i1.406
     [Google Scholar]
  159. WuC.H. LinK.L. LongC.Y. FengC.W. The neuroprotective effect of isotetrandrine on Parkinson’s disease via anti-inflammation and antiapoptosis in vitro and in vivo.Parkinsons Dis.2023202311210.1155/2023/8444153 37854894
     [Google Scholar]
  160. BarbosaJ.S. NinkovicJ. Adult neural stem cell behavior underlying constitutive and restorative neurogenesis in zebrafish.Neurogenesis201631e114810110.1080/23262133.2016.1148101 27606336
     [Google Scholar]
  161. GodoyR. HuaK. KalynM. CussonV.M. AnismanH. EkkerM. Dopaminergic neurons regenerate following chemogenetic ablation in the olfactory bulb of adult Zebrafish (Danio rerio).Sci. Rep.20201011282510.1038/s41598‑020‑69734‑0 32733000
     [Google Scholar]
  162. MarquesI.J. LupiE. MercaderN. Model systems for regeneration: Zebrafish.Development201914618dev16769210.1242/dev.167692 31540899
     [Google Scholar]
  163. CaldwellL.J. DaviesN.O. CavoneL. Regeneration of dopaminergic neurons in adult zebrafish depends on immune system activation and differs for distinct populations.J. Neurosci.201939244694471310.1523/JNEUROSCI.2706‑18.2019 30948475
     [Google Scholar]
  164. AlunniA. Bally-CuifL. A comparative view of regenerative neurogenesis in vertebrates.Development2016143574175310.1242/dev.122796 26932669
     [Google Scholar]
  165. KyritsisN. KizilC. ZocherS. Acute inflammation initiates the regenerative response in the adult zebrafish brain.Science201233861121353135610.1126/science.1228773 23138980
     [Google Scholar]
  166. OhnmachtJ YangY MaurerGW Spinal motor neurons are regenerated after mechanical lesion and genetic ablation in larval zebrafish.Development20161439dev.12915510.1242/dev.129155 26965370
     [Google Scholar]
  167. YamamotoK. RuuskanenJ.O. WullimannM.F. VernierP. Two tyrosine hydroxylase genes in vertebrates.Mol. Cell. Neurosci.201043439440210.1016/j.mcn.2010.01.006 20123022
     [Google Scholar]
  168. HughesG.L. LonesM.A. BedderM. CurrieP.D. SmithS.L. PownallM.E. Machine learning discriminates a movement disorder in a zebrafish model of Parkinson’s disease.Dis. Model. Mech.20201310dmm04581510.1242/dmm.045815 32859696
     [Google Scholar]
  169. ShehwanaH. KonuO. Comparative transcriptomics between zebrafish and mammals: A roadmap for discovery of conserved and unique signaling pathways in physiology and disease.Front. Cell Dev. Biol.20197510.3389/fcell.2019.00005 30775367
     [Google Scholar]
  170. HoweK. ClarkM.D. TorrojaC.F. The zebrafish reference genome sequence and its relationship to the human genome.Nature2013496744649850310.1038/nature12111 23594743
     [Google Scholar]
  171. KalueffA.V. CachatJ.M. Zebrafish models in neurobehavioral research.Springer201110.1007/978‑1‑60761‑922‑2
     [Google Scholar]
  172. d’AmoraM. GiordaniS. The utility of zebrafish as a model for screening developmental neurotoxicity.Front. Neurosci.20181297610.3389/fnins.2018.00976 30618594
     [Google Scholar]
  173. GilbertM.J.H. ZerullaT.C. TierneyK.B. Zebrafish (Danio rerio) as a model for the study of aging and exercise: Physical ability and trainability decrease with age.Exp. Gerontol.20145010611310.1016/j.exger.2013.11.013 24316042
     [Google Scholar]
  174. NjiwaJ.R.K. MüllerP. KleinR. Life cycle stages and length of zebrafish (Danio rerio) exposed to DDT.J. Health Sci.200450322022510.1248/jhs.50.220
     [Google Scholar]
  175. AvdeshA. ChenM. Martin-IversonM.T. Regular care and maintenance of a zebrafish (Danio rerio) laboratory: An introduction.J. Vis. Exp.201269e4196 23183629
     [Google Scholar]
  176. ArslanB.K. EdmondsonD.E. Expression of zebrafish (Danio rerio) monoamine oxidase (MAO) in Pichia pastoris: Purification and comparison with human MAO A and MAO B.Protein Expr. Purif.201070229029710.1016/j.pep.2010.01.005 20079438
     [Google Scholar]
  177. FierroA. MontecinosA. Gómez-MolinaC. Similarities between the binding sites of monoamine oxidase (MAO) from different species. Is zebrafish a useful model for the discovery of novel MAO inhibitors.An integrated view of the molecular recognition and toxinology From analytical procedures to biomedical applications.RijekaInTech2013
     [Google Scholar]
  178. KalueffA.V. StewartA.M. GerlaiR. Zebrafish as an emerging model for studying complex brain disorders.Trends Pharmacol. Sci.2014352637510.1016/j.tips.2013.12.002 24412421
     [Google Scholar]
  179. SaleemS. KannanR.R. Zebrafish: An emerging real-time model system to study Alzheimer’s disease and neurospecific drug discovery.Cell Death Discov.2018414510.1038/s41420‑018‑0109‑7 30302279
     [Google Scholar]
  180. GoldsmithJ.R. JobinC. Think small: Zebrafish as a model system of human pathology.J. Biomed. Biotechnol.2012201211210.1155/2012/817341 22701308
     [Google Scholar]
  181. LardelliM. Using zebrafish in human disease research: Some advantages, disadvantages and ethical considerations.Proceedings of 2008 ANZCCART ConferenceAuckland, New Zealand20082328
     [Google Scholar]
  182. VazR.L. OuteiroT.F. FerreiraJ.J. Zebrafish as an animal model for drug discovery in Parkinson’s disease and other movement disorders: A systematic review.Front. Neurol.2018934710.3389/fneur.2018.00347 29910763
     [Google Scholar]
/content/journals/cnsnddt/10.2174/0118715273367688250528122144
Loading
Zebrafish-Based Parkinson's Disease Models: Unveiling Genetic Mechanisms and Therapeutic Pathways
CNS Neurol. Disord. Drug Targets 24, 900 (2025); https://doi.org/10.2174/0118715273367688250528122144
/content/journals/cnsnddt/10.2174/0118715273367688250528122144
/content/journals/cnsnddt/10.2174/0118715273367688250528122144
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): disease modeling; dopamine; genetic similarity; herbal treatment; neurodegeneration; neurodevelopment; neurotoxins; Parkinson’s disease; PD models; therapeutic strategies; Zebrafish

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test