Browse > Article
http://dx.doi.org/10.47853/FAS.2022.e11

Fishing for synucleinopathy models  

Noor, Suzita Mohd (Department of Biomedical Science, Faculty of Medicine, University of Malaya)
Norazit, Anwar (Department of Biomedical Science, Faculty of Medicine, University of Malaya)
Publication Information
Fisheries and Aquatic Sciences / v.25, no.3, 2022 , pp. 117-139 More about this Journal
Abstract
Synucleinopathies such as Parkinson's disease (PD) are incurable neurodegenerative conditions characterised by the abnormal aggregation of α-synuclein protein in neuronal cells. In PD, fibrillary synuclein aggregation forms Lewy bodies and Lewy neurites in the substantia nigra and cortex on the brain. Dementia with Lewy bodies and multiple system atrophy are also associated with α-synuclein protein abnormalities. α-synuclein is one of three synuclein proteins, and while its precise function is still unknown, one hypothesis posits that α-synuclein propagates from the enteric nervous system through the vagus nerve and into the brain, resulting in synucleinopathy. Studies on synucleinopathies should thus encompass not only the central nervous system but must necessarily include the gut and microbiome. The zebrafish (Danio rerio) is a well-established model for human neuronal pathologies and have been used in studies ranging from genetic models of hereditary disorders to neurotoxin-induced neurodegeneration as well as gut-brain-axis studies. There is significant genetic homology between zebrafish and mammalian vertebrates which is what makes the zebrafish so amenable to modelling human conditions but in the case of synucleinopathies, the zebrafish notably does not possess an α-synuclein homolog. Synuclein orthologs are present in the zebrafish however, and transgenic zebrafish that carry human α-synuclein have been generated. In addition, the zebrafish is a highly advantageous model and ideal replacement for reducing the use of mammalian models. This review discusses the application of the zebrafish as a model for synucleinopathies in efforts to further understand synuclein function and explore therapeutic strategies.
Keywords
Zebrafish; Synucleins; Synucleinopathy; Gut-brain-axis;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Engelender S, Kaminsky Z, Guo X, Sharp AH, Amaravi RK, Kleiderlein JJ, et al. Synphilin-1 associates with α-synuclein and promotes the formation of cytosolic inclusions. Nat Genet. 1999;22:110-4.   DOI
2 Engelender S, Wanner T, Kleiderlein JJ, Wakabayashi K, Tsuji S, Takahashi H, et al. Organization of the human synphilin-1 gene, a candidate for Parkinson's disease. Mamm Genome. 2000;11:763-6.   DOI
3 Engeszer RE, Patterson LB, Rao AA, Parichy DM. Zebrafish in the wild: a review of natural history and new notes from the field. Zebrafish. 2007;4:21-40.   DOI
4 Fan Y, Limprasert P, Murray IVJ, Smith AC, Lee VMY, Trojanowski JQ, et al. β-Synuclein modulates α-synuclein neurotoxicity by reducing α-synuclein protein expression. Hum Mol Genet. 2006;15:3002-11.   DOI
5 Luke GA, Ryan MD. Using the 2A protein coexpression system: multicistronic 2A vectors expressing gene(s) of interest and reporter proteins. In: Damoiseaux R, Hasson S, editors. Reporter gene assays: methods and protocols. New York, NY: Humana Press/Springer; 2018. p. 31-48.
6 Flinn L, Bretaud S, Lo C, Ingham PW, Bandmann O. Zebrafish as a new animal model for movement disorders. J Neurochem. 2008;106:1991-7.   DOI
7 Lu J, Peatman E, Tang H, Lewis J, Liu Z. Profiling of gene duplication patterns of sequenced teleost genomes: evidence for rapid lineage-specific genome expansion mediated by recent tandem duplications. BMC Genomics. 2012;13:246.   DOI
8 Lionnet A, Leclair-Visonneau L, Neunlist M, Murayama S, Takao M, Adler CH, et al. Does Parkinson's disease start in the gut? Acta Neuropathol. 2018;135:1-12.   DOI
9 Strahle U, Scholz S, Geisler R, Greiner P, Hollert H, Rastegar S, et al. Zebrafish embryos as an alternative to animal experiments-a commentary on the definition of the onset of protected life stages in animal welfare regulations. Reprod Toxicol. 2012;33:128-32.   DOI
10 Volff JN. Genome evolution and biodiversity in teleost fish. Heredity. 2005;94:280-94.   DOI
11 Maroteaux L, Campanelli JT, Scheller RH. Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci. 1988;8:2804-15.   DOI
12 Martins T, Valentim AM, Pereira N, Antunes LM. Anaesthesia and analgesia in laboratory adult zebrafish: a question of refinement. Lab Anim. 2016;50:476-88.   DOI
13 Piovesan A, Antonaros F, Vitale L, Strippoli P, Pelleri MC, Caracausi M. Human protein-coding genes and gene feature statistics in 2019. BMC Res Notes. 2019;12:315.   DOI
14 Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997;276:2045-7.   DOI
15 Prabhudesai S, Bensabeur FZ, Abdullah R, Basak I, Baez S, Alves G, et al. LRRK2 knockdown in zebrafish causes developmental defects, neuronal loss, and synuclein aggregation. J Neurosci Res. 2016;94:717-35.   DOI
16 Das SK, Aparna S, Patri M. Chronic waterborne exposure to benzo[a]pyrene induces locomotor dysfunction and development of neurodegenerative phenotypes in zebrafish. Neurosci Lett. 2020;716:134646.   DOI
17 Coon EA, Singer W. Synucleinopathies. Continuum (Minneap Minn). 2020;26:72-92.   DOI
18 Corey DR, Abrams JM. Morpholino antisense oligonucleotides: tools for investigating vertebrate development. Genome Biol. 2001;2:reviews1015.1.
19 Cornet C, Di Donato V, Terriente J. Combining zebrafish and CRISPR/Cas9: toward a more efficient drug discovery pipeline. Front Pharmacol. 2018;9:703.   DOI
20 Dauer W, Przedborski S. Parkinson's disease: mechanisms and models. Neuron. 2003;39:889-909.   DOI
21 Davis DJ, Bryda EC, Gillespie CH, Ericsson AC. Microbial modulation of behavior and stress responses in zebrafish larvae. Behav Brain Res. 2016;311:219-27.   DOI
22 de Abreu MS, Giacomini ACVV, Sysoev M, Demin KA, Alekseeva PA, Spagnoli ST, et al. Modeling gut-brain interactions in zebrafish. Brain Res Bull. 2019;148:55-62.   DOI
23 Dickson DW, Lin W, Liu WK, Yen SH. Multiple system atrophy: a sporadic synucleinopathy. Brain Pathol. 1999;9:721-32.   DOI
24 van Ham TJ, Brady CA, Kalicharan RD, Oosterhof N, Kuipers J, Veenstra-Algra A, et al. Intravital correlated microscopy reveals differential macrophage and microglial dynamics during resolution of neuroinflammation. Dis Models Mech. 2014;7:857-69.   DOI
25 Godoy R, Hua K, Kalyn M, Cusson VM, Anisman H, Ekker M. Dopaminergic neurons regenerate following chemogenetic ablation in the olfactory bulb of adult Zebrafish (Danio rerio). Sci Rep. 2020;10:12825.   DOI
26 Fontana BD, Mezzomo NJ, Kalueff AV, Rosemberg DB. The developing utility of zebrafish models of neurological and neuropsychiatric disorders: a critical review. Exp Neurol. 2018;299:157-71.   DOI
27 Ganz J. Gut feelings: studying enteric nervous system development, function, and disease in the zebrafish model system. Dev Dyn. 2018;247:268-78.   DOI
28 George JM. The synucleins. Genome Biol. 2001;3:reviews3002.1-3002.6.   DOI
29 Goedert M. Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci. 2001;2:492-501.   DOI
30 Goedert M, Spillantini MG. Synucleinopathies and tauopathies. In: Brady ST, Siegel GJ, Albers RW, editors. Basic neurochemistry. Amsterdam: Elsevier; 2012. p. 829-43.
31 Gorostidi A, Bergareche A, Ruiz-Martinez J, Marti-Masso JF, Cruz M, Varghese S, et al. α-Synuclein levels in blood plasma from LRRK2 mutation carriers. PLOS ONE. 2012;7:e52312.   DOI
32 Haikal C, Chen QQ, Li JY. Microbiome changes: an indicator of Parkinson's disease? Transl Neurodegener. 2019;8:38.   DOI
33 Hashimoto M, Spada ARL. β-Synuclein in the pathogenesis of Parkinson's disease and related α-synucleinopathies: emerging roles and new directions. Future Neurol. 2012;7:155-63.   DOI
34 Goedert M, Masuda-Suzukake M, Falcon B. Like prions: the propagation of aggregated tau and α-synuclein in neurodegeneration. Brain. 2016;140:266-78.   DOI
35 Rey NL, George S, Brundin P. Review: spreading the word: precise animal models and validated methods are vital when evaluating prion-like behaviour of alpha-synuclein. Neuropathol Appl Neurobiol. 2016;42:51-76.   DOI
36 Proukakis C, Dudzik CG, Brier T, MacKay DS, Cooper JM, Millhauser GL, et al. A novel α-synuclein missense mutation in Parkinson disease. Neurology. 2013;80:1062-4.   DOI
37 Quilty MC, King AE, Gai WP, Pountney DL, West AK, Vickers JC, et al. Alpha-synuclein is upregulated in neurones in response to chronic oxidative stress and is associated with neuroprotection. Exp Neurol. 2006;199:249-56.   DOI
38 Recchia A, Debetto P, Negro A, Guidolin D, Skaper SD, Giusti P. Alpha-synuclein and Parkinson's disease. FASEB J. 2004;18:617-26.   DOI
39 Rolig AS, Mittge EK, Ganz J, Troll JV, Melancon E, Wiles TJ, et al. The enteric nervous system promotes intestinal health by constraining microbiota composition. PLOS Biol. 2017;15:e2000689.   DOI
40 Luo C, Rajput AH, Akhtar S, Rajput A. α-Synuclein and tyrosine hydroxylase expression in acute rotenone toxicity. Int J Mol Med. 2007;19:517-21.
41 Lv DJ, Li LX, Chen J, Wei SZ, Wang F, Hu H, et al. Sleep deprivation caused a memory defects and emotional changes in a rotenone-based zebrafish model of Parkinson's disease. Behav Brain Res. 2019;372:112031.   DOI
42 Ma Q, Xing C, Long W, Wang HY, Liu Q, Wang RF. Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis. J Neuroinflammation. 2019;16:53.   DOI
43 Kuil LE, Chauhan RK, Cheng WW, Hofstra RMW, Alves MM. Zebrafish: a model organism for studying enteric nervous system development and disease. Front Cell Dev Biol. 2021;8:629073.   DOI
44 Koppel N, Maini Rekdal V, Balskus EP. Chemical transformation of xenobiotics by the human gut microbiota. Science. 2017;356:eaag2770.   DOI
45 Kostyuk AI, Panova AS, Kokova AD, Kotova DA, Maltsev DI, Podgorny OV, et al. In vivo imaging with genetically encoded redox biosensors. Int J Mol Sci. 2020;21:8164.   DOI
46 Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kosel S, et al. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet. 1998;18:106-8.   DOI
47 Liu J, Xu F, Nie Z, Shao L. Gut microbiota approach-a new strategy to treat Parkinson's disease. Front Cell Infect Microbiol. 2020;10:570658.   DOI
48 Madden JC, Hewitt M, Przybylak K, Vandebriel RJ, Piersma AH, Cronin MTD. Strategies for the optimisation of in vivo experiments in accordance with the 3Rs philosophy. Regul Toxicol Pharmacol. 2012;63:140-54.   DOI
49 Hoppe SO, Uzunoglu G, Nussbaum-Krammer C. α-Synuclein strains: does amyloid conformation explain the heterogeneity of synucleinopathies? Biomolecules. 2021;11:931.   DOI
50 Kurian MA, Morgan NV, MacPherson L, Foster K, Peake D, Gupta R, et al. Phenotypic spectrum of neurodegeneration associated with mutations in the PLA2G6 gene (PLAN). Neurology. 2008;70:1623-9.   DOI
51 Makhija DT, Jagtap AG. Studies on sensitivity of zebrafish as a model organism for Parkinson's disease: comparison with rat model. J Pharmacol Pharmacother. 2014;5:39-46.   DOI
52 Punsoni M, Friedman JH, Resnick M, Donahue JE, Yang DF, Stopa EG. Enteric pathologic manifestations of alpha-synucleinopathies. Appl Immunohistochem Mol Morphol. 2019;27:543-8.   DOI
53 Rodriguez L, Marano MM, Tandon A. Import and export of misfolded α-synuclein. Front Neurosci. 2018;12:344.   DOI
54 Smith WW, Liu Z, Liang Y, Masuda N, Swing DA, Jenkins NA, et al. Synphilin-1 attenuates neuronal degeneration in the A53T alpha-synuclein transgenic mouse model. Hum Mol Genet. 2010;19:2087-98.   DOI
55 Taymans JM, Cookson MR. Mechanisms in dominant parkinsonism: the toxic triangle of LRRK2, α-synuclein, and tau. BioEssays. 2010;32:227-35.   DOI
56 Hernandez-Vargas RH, Fonseca-Ornelas L, Lopez-Gonzalez I, Riesgo-Escovar J, Zurita M, Reynaud E. Synphilin suppresses α-synuclein neurotoxicity in a Parkinson's disease Drosophila model. Genesis. 2011;49:392-402.   DOI
57 Gregory A, Kurian MA, Maher ER, Hogarth P, Hayflick SJ. PLA2G6-associated neurodegeneration. Seattle, WA: University of Washington; 2017.
58 Zhu J, Xia R, Liu Z, Shen J, Gong X, Hu Y, et al. Fenvalerate triggers Parkinson-like symptom during zebrafish development through initiation of autophagy and p38 MAPK/mTOR signaling pathway. Chemosphere. 2020;243:125336.   DOI
59 Ma PM. Catecholaminergic systems in the zebrafish. IV. Organization and projection pattern of dopaminergic neurons in the diencephalon. J Comp Neurol. 2003;460:13-37.   DOI
60 Lulla A, Barnhill L, Bitan G, Ivanova MI, Nguyen B, O'Donnell K, et al. Neurotoxicity of the Parkinson disease-associated pesticide ziram is synuclein-dependent in zebrafish embryos. Environ Health Perspect. 2016;124:1766-75.   DOI
61 Milanese C, Sager JJ, Bai Q, Farrell TC, Cannon JR, Greenamyre JT, et al. Hypokinesia and reduced dopamine levels in zebrafish lacking β- and γ1-synucleins. J Biol Chem. 2012;287:2971-83.   DOI
62 Ishikawa-Ankerhold HC, Ankerhold R, Drummen GPC. Advanced fluorescence microscopy techniques-FRAP, FLIP, FLAP, FRET and FLIM. Molecules. 2012;17:4047-132.   DOI
63 Khotimah H, Sumitro SB, Widodo MA. Zebrafish Parkinson's model: rotenone decrease motility, dopamine, and increase α-synuclein aggregation and apoptosis of zebrafish brain. Int J Pharm Tech Res. 2015b;8:614-21.
64 Nietzel T, Elsasser M, Ruberti C, Steinbeck J, Ugalde JM, Fuchs P, et al. The fluorescent protein sensor roGFP2-Orp1 monitors in vivo H2O2 and thiol redox integration and elucidates intracellular H2O2 dynamics during elicitor-induced oxidative burst in Arabidopsis. New Phytol. 2019;221:1649-64.   DOI
65 Rietdijk CD, Perez-Pardo P, Garssen J, van Wezel RJA, Kraneveld AD. Exploring Braak's Hypothesis of Parkinson's disease. Front Neurol. 2017;8:37.
66 Lennaerts-Kats H, Ebenau A, Steppe M, van der Steen JT, Meinders MJ, Vissers K, et al. "How long can I carry on?" The need for palliative care in Parkinson's disease: a qualitative study from the perspective of bereaved family caregivers. J Parkinsons Dis. 2020;10:1631-42.   DOI
67 Lavedan C, Leroy E, Dehejia A, Buchholtz S, Dutra A, Nussbaum RL, et al. Identification, localization and characterization of the human γ-synuclein gene. Hum Genet. 1998;103:106-12.   DOI
68 Lee HJ, Kim C, Lee SJ. Alpha-synuclein stimulation of astrocytes: potential role for neuroinflammation and neuroprotection. Oxid Med Cell Longev. 2010;3:283-7.   DOI
69 Lee JG, Cho HJ, Jeong YM, Lee JS. Genetic approaches using zebrafish to study the microbiota-gut-brain axis in neurological disorders. Cells. 2021;10:566.   DOI
70 Leong SL, Cappai R, Barnham KJ, Pham CLL. Modulation of alpha-synuclein aggregation by dopamine: a review. Neurochem Res. 2009;34:1838-46.   DOI
71 Li J, Uversky VN, Fink AL. Conformational behavior of human α-synuclein is modulated by familial Parkinson's disease point mutations A30P and A53T. Neurotoxicology. 2002;23:553-67.   DOI
72 Li N, Stewart T, Sheng L, Shi M, Cilento EM, Wu Y, et al. Immunoregulation of microglial polarization: an unrecognized physiological function of α-synuclein. J Neuroinflammation. 2020;17:272.   DOI
73 Elgar G. Plenty more fish in the sea: comparative and functional genomics using teleost models. Brief Funct Genomic Proteomic. 2004;3:15-25.   DOI
74 Ding Y, Lei L, Lai C, Tang Z. Tau protein and zebrafish models for tau-induced neurodegeneration. J Alzheimers Dis. 2019;69:339-53.   DOI
75 Du Y, Guo Q, Shan M, Wu Y, Huang S, Zhao H, et al. Spatial and temporal distribution of dopaminergic neurons during development in zebrafish. Front Neuroanat. 2016;10:115.
76 Dukes AA, Bai Q, Van Laar VS, Zhou Y, Ilin V, David CN, et al. Live imaging of mitochondrial dynamics in CNS dopaminergic neurons in vivo demonstrates early reversal of mitochondrial transport following MPP+ exposure. Neurobiol Dis. 2016;95:238-49.   DOI
77 Mbefo MK, Paleologou KE, Boucharaba A, Oueslati A, Schell H, Fournier M, et al. Phosphorylation of synucleins by members of the Polo-like kinase family. J Biol Chem. 2010;285:2807-22.   DOI
78 Matsui H, Matsui N. Cerebrospinal fluid injection into adult zebrafish for disease research. J Neural Transm. 2017;124:1627-33.   DOI
79 Matsui H, Sugie A. An optimized method for counting dopaminergic neurons in zebrafish. PLOS ONE. 2017;12:e0184363.   DOI
80 Maximino C, de Brito TM, da Silva Batista AW, Herculano AM, Morato S, Gouveia A Jr. Measuring anxiety in zebrafish: a critical review. Behav Brain Res. 2010;214:157-71.   DOI
81 Mehra S, Sahay S, Maji SK. α-Synuclein misfolding and aggregation: implications in Parkinson's disease pathogenesis. Biochim Biophys Acta Proteins Proteomics. 2019;1867:890-908.   DOI
82 Melki R. Role of different alpha-synuclein strains in synucleinopathies, similarities with other neurodegenerative diseases. J Parkinsons Dis. 2015;5:217-27.   DOI
83 Milanese C, Cerri S, Ulusoy A, Gornati SV, Plat A, Gabriels S, et al. Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson's disease. Cell Death Dis. 2018;9:818.   DOI
84 Mohanta L, Das BC, Patri M. Microbial communities modulating brain functioning and behaviors in zebrafish: a mechanistic approach. Microb Pathog. 2020;145:104251.   DOI
85 Moulton JD. Using morpholinos to control gene expression. Curr Protoc Nucleic Acid Chem. 2017;68:4.30.1-4.30.29.   DOI
86 Moussavi Nik SH, Newman M, Ganesan S, Chen M, Martins R, Verdile G, et al. Hypoxia alters expression of zebrafish microtubule-associated protein tau (mapta, maptb) gene transcripts. BMC Res Notes. 2014;7:767.   DOI
87 Lesage S, Anheim M, Letournel F, Bousset L, Honore A, Rozas N, et al. G51D α-synuclein mutation causes a novel parkinsonian-pyramidal syndrome. Ann Neurol. 2013;73:459-71.   DOI
88 Lehtonen S, Sonninen TM, Wojciechowski S, Goldsteins G, Koistinaho J. Dysfunction of cellular proteostasis in Parkinson's disease. Front Neurosci. 2019;13:457.   DOI
89 Greggio E, Cookson MR. Leucine-rich repeat kinase 2 mutations and Parkinson's disease: three questions. ASN Neuro. 2009;1:AN20090007.   DOI
90 Lee VMY, Trojanowski JQ. Progress from Alzheimer's tangles to pathological tau points towards more effective therapies now. J Alzheimers Dis. 2006;9(3 Suppl):257-62.   DOI
91 Dodiya HB, Forsyth CB, Voigt RM, Engen PA, Patel J, Shaikh M, et al. Chronic stress-induced gut dysfunction exacerbates Parkinson's disease phenotype and pathology in a rotenone-induced mouse model of Parkinson's disease. Neurobiol Dis. 2020;135:104352.   DOI
92 Bernis ME, Babila JT, Breid S, Wusten KA, Wullner U, Tamguney G. Prion-like propagation of human brain-derived alpha-synuclein in transgenic mice expressing human wild-type alpha-synuclein. Acta Neuropathol Commun. 2015;3:75.   DOI
93 Beyer K. α-Synuclein structure, posttranslational modification and alternative splicing as aggregation enhancers. Acta Neuropathol. 2006;112:237-51.   DOI
94 Houlden H, Singleton AB. The genetics and neuropathology of Parkinson's disease. Acta Neuropathol. 2012;124:325-38.   DOI
95 Kaur U, Lee JC. Membrane interactions of α-synuclein probed by neutrons and photons. Acc Chem Res. 2021;54:302-10.   DOI
96 Oueslati A, Schneider BL, Aebischer P, Lashuel HA. Polo-like kinase 2 regulates selective autophagic α-synuclein clearance and suppresses its toxicity in vivo. Proc Natl Acad Sci USA. 2013;110:E3945-54.
97 Perez RG, Waymire JC, Lin E, Liu JJ, Guo F, Zigmond MJ. A role for alpha-synuclein in the regulation of dopamine biosynthesis. J Neurosci. 2002;22:3090-9.   DOI
98 Hawkes CH, Del Tredici K, Braak H. Parkinson's disease: a dual-hit hypothesis. Neuropathol Appl Neurobiol. 2007;33:599-614.   DOI
99 Hoenen C, Gustin A, Birck C, Kirchmeyer M, Beaume N, Felten P, et al. Alpha-synuclein proteins promote pro-inflammatory cascades in microglia: stronger effects of the A53T mutant. PLOS ONE. 2016;11:e0162717.   DOI
100 Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M, et al. The zebrafish reference genome sequence and its relationship to the human genome. Nature. 2013;496(7446):498-503.   DOI
101 Howe K. Chapter 31 - The zebrafish genome sequencing project: bioinformatics resources. In: Gerlai RT, editor. Behavioral and neural genetics of zebrafish. London: Academic Press; 2020. p. 551-62.
102 Hruska KS, LaMarca ME, Scott CR, Sidransky E. Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA). Hum Mutat. 2008;29:567-83.   DOI
103 Hu Q, Guo F, Zhao F, Fu Z. Effects of titanium dioxide nanoparticles exposure on Parkinsonism in zebrafish larvae and PC12. Chemosphere. 2017;173:373-9.   DOI
104 Inglis KJ, Chereau D, Brigham EF, Chiou SS, Schobel S, Frigon NL, et al. Polo-like kinase 2 (PLK2) phosphorylates α-synuclein at serine 129 in central nervous system. J Biol Chem. 2009;284:2598-602.   DOI
105 Innos J, Hickey MA. Using rotenone to model Parkinson's disease in mice: a review of the role of pharmacokinetics. Chem Res Toxicol. 2021;34:1223-39.   DOI
106 Usmani SM, Mempel TR. Chapter 10 - Intravital microscopy. In: Ross BD, Gambhir SS, editors. Molecular imaging: principles and practice Volume 2. London: Academic Press; 2021. p. 167-92.
107 Borghammer P, Horsager J, Andersen K, Van Den Berge N, Raunio A, Murayama S, et al. Neuropathological evidence of body-first vs. brain-first Lewy body disease. Neurobiol Dis. 2021;161:105557.   DOI
108 Beyer K, Ispierto L, Latorre P, Tolosa E, Ariza A. Alpha- and beta-synuclein expression in Parkinson disease with and without dementia. J Neurol Sci. 2011;310:112-7.   DOI
109 Bill BR, Petzold AM, Clark KJ, Schimmenti LA, Ekker SC. A primer for morpholino use in zebrafish. Zebrafish. 2009;6:69-77.   DOI
110 Blader P, Strahle U. Zebrafish developmental genetics and central nervous system development. Hum Mol Genet. 2000;9:945-51.   DOI
111 Borrelli L, Aceto S, Agnisola C, De Paolo S, Dipineto L, Stilling RM, et al. Probiotic modulation of the microbiota-gut-brain axis and behaviour in zebrafish. Sci Rep. 2016;6:30046.   DOI
112 Shaltiel-Karyo R, Frenkel-Pinter M, Egoz-Matia N, Frydman-Marom A, Shalev DE, Segal D, et al. Inhibiting α-synuclein oligomerization by stable cell-penetrating β-synuclein fragments recovers phenotype of Parkinson's disease model flies. PLOS ONE. 2010;5:e13863.   DOI
113 Hashimoto M, Rockenstein E, Mante M, Mallory M, Masliah E. β-Synuclein inhibits α-synuclein aggregation: a possible role as an anti-parkinsonian factor. Neuron. 2001;32:213-23.   DOI
114 Jiang W, Li J, Zhang Z, Wang H, Wang Z. Epigenetic upregulation of alpha-synuclein in the rats exposed to methamphetamine. Eur J Pharmacol. 2014;745:243-8.   DOI
115 Jakes R, Spillantini MG, Goedert M. Identification of two distinct synucleins from human brain. FEBS Lett. 1994;345:27-32.   DOI
116 Jo E, McLaurin J, Yip CM, St. George-Hyslop P, Fraser PE. alpha-Synuclein membrane interactions and lipid specificity. J Biol Chem. 2000;275:34328-34.   DOI
117 Adams-Carr KL, Bestwick JP, Shribman S, Lees A, Schrag A, Noyce AJ. Constipation preceding Parkinson's disease: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2016;87:710-6.   DOI
118 Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990;215:403-10.   DOI
119 Beach TG, Adler CH, Sue LI, Shill HA, Driver-Dunckley E, Mehta SH, et al. Vagus nerve and stomach synucleinopathy in Parkinson's disease, incidental Lewy body disease, and normal elderly subjects: evidence against the "body-first" hypothesis. J Parkinsons Dis. 2021;11:1833-43.   DOI
120 Abeliovich A, Schmitz Y, Farinas I, Choi-Lundberg D, Ho WH, Castillo PE, et al. Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron. 2000;25:239-52.   DOI
121 Ahmad M, Attoub S, Singh MN, Martin FL, El-Agnaf OMA. Gamma-synuclein and the progression of cancer. FASEB J. 2007;21:3419-30.   DOI
122 Alestrom P, D'Angelo L, Midtlyng PJ, Schorderet DF, Schulte-Merker S, Sohm F, et al. Zebrafish: housing and husbandry recommendations. Lab Anim. 2020;54:213-24.   DOI
123 Keatinge M, Bui H, Menke A, Chen YC, Sokol AM, Bai Q, et al. Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provide evidence of early microglial activation preceding alpha-synuclein-independent neuronal cell death. Hum Mol Genet. 2015;24:6640-52.   DOI
124 Johnson ME, Stringer A, Bobrovskaya L. Rotenone induces gastrointestinal pathology and microbiota alterations in a rat model of Parkinson's disease. Neurotoxicology. 2018;65:174-85.   DOI
125 Kalueff AV, Stewart AM, Gerlai R. Zebrafish as an emerging model for studying complex brain disorders. Trends Pharmacol Sci. 2014;35:63-75.   DOI
126 Kaur G, Behl T, Bungau S, Kumar A, Uddin MS, Mehta V, et al. Dysregulation of the gut-brain axis, dysbiosis and influence of numerous factors on gut microbiota associated Parkinson's disease. Curr Neuropharmacol. 2021;19:233-47.   DOI
127 Keller JM, Keller ET. The use of mature zebrafish (Danio rerio) as a model for human aging and disease. In: Ram JL, Conn PM, editors. Conn's handbook of models for human aging. London: Academic Press; 2018. p. 351-9.
128 Khotimah H, Ali M, Sumitro SB, Widodo MA. Decreasing α-synuclein aggregation by methanolic extract of Centella asiatica in zebrafish Parkinson's model. Asian Pac J Trop Biomed. 2015a;5:948-54.   DOI
129 Kimmel CB. Genetics and early development of zebrafish. Trends Genet. 1989;5:283-8.   DOI
130 Kimmel CB. Patterning the brain of the zebrafish embryo. Annnu Rev Neurosci. 1993;16:707-32.   DOI
131 Johnson ME, Bobrovskaya L. An update on the rotenone models of Parkinson's disease: their ability to reproduce the features of clinical disease and model gene-environment interactions. Neurotoxicology. 2015;46:101-16.   DOI
132 Bai Q, Burton EA. Zebrafish models of Tauopathy. Biochim Biophys Acta 2011;1812:353-63.   DOI
133 Allison JR, Rivers RC, Christodoulou JC, Vendruscolo M, Dobson CM. A relationship between the transient structure in the monomeric state and the aggregation propensities of α-synuclein and β-synuclein. Biochemistry. 2014;53:7170-83.   DOI
134 Appel-Cresswell S, Vilarino-Guell C, Encarnacion M, Sherman H, Yu I, Shah B, et al. Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease. Mov Disord. 2013;28:811-3.   DOI
135 Asakawa K, Kawakami K. The Tol2-mediated Gal4-UAS method for gene and enhancer trapping in zebrafish. Methods. 2009;49:275-81.   DOI
136 Baker PA, Meyer MD, Tsang A, Uribe RA. Immunohistochemical and ultrastructural analysis of the maturing larval zebrafish enteric nervous system reveals the formation of a neuropil pattern. Sci Rep. 2019;9:6941.   DOI
137 Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF. Stages of embryonic development of the zebrafish. Dev Dyn. 1995;203:253-310.   DOI
138 Marx FP, Holzmann C, Strauss KM, Li L, Eberhardt O, Gerhardt E, et al. Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease. Hum Mol Genet. 2003;12:1223-31.   DOI
139 Chepelev NL, Moffat ID, Bowers WJ, Yauk CL. Neurotoxicity may be an overlooked consequence of benzo[a]pyrene exposure that is relevant to human health risk assessment. Mutat Res Rev Mutat Res. 2015;764:64-89.   DOI
140 Anderson JP, Walker DE, Goldstein JM, de Laat R, Banducci K, Caccavello RJ, et al. Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J Biol Chem. 2006;281:29739-52.   DOI
141 Barbazuk WB, Korf I, Kadavi C, Heyen J, Tate S, Wun E, et al. The syntenic relationship of the zebrafish and human genomes. Genome Res. 2000;10:1351-8.   DOI
142 Cuomo M, Borrelli L, Della Monica R, Coretti L, De Riso G, D'Angelo Lancellotti di Durazzo L, et al. DNA methylation profiles of Tph1A and BDNF in gut and brain of L. Rhamnosus-treated zebrafish. Biomolecules. 2021;11:142.   DOI
143 Dehal P, Boore JL. Two rounds of whole genome duplication in the ancestral vertebrate. PLOS Biol. 2005;3:e314.   DOI
144 Ng CH, Basil AH, Hang L, Tan R, Goh KL, O'Neill S, et al. Genetic or pharmacological activation of the Drosophila PGC-1α ortholog spargel rescues the disease phenotypes of genetic models of Parkinson's disease. Neurobiol Aging. 2017;55:33-7.   DOI
145 Chen M, Martins RN, Lardelli M. Complex splicing and neural expression of duplicated tau genes in zebrafish embryos. J Alzheimers Dis. 2009a;18:305-17.   DOI
146 Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinson's disease. J Parkinsons Dis. 2013;3:461-91.   DOI
147 Ingelsson M. Alpha-synuclein oligomers-neurotoxic molecules in Parkinson's disease and other lewy body disorders. Front Neurosci. 2016;10:408.   DOI
148 Kumar A, Anuppalle M, Maddirevula S, Huh TL, Choe J, Rhee M. Peli1b governs the brain patterning via ERK signaling pathways in zebrafish embryos. Gene. 2019;694:1-6.   DOI
149 Mudo G, Makela J, Di Liberto V, Tselykh TV, Olivieri M, Piepponen P, et al. Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson's disease. Cell Mol Life Sci. 2012;69:1153-65.   DOI
150 Musgrove REJ, King AE, Dickson TC. Neuroprotective upregulation of endogenous alpha-synuclein precedes ubiquitination in cultured dopaminergic neurons. Neurotox Res. 2011;19:592-602.   DOI
151 Burre J, Sharma M, Sudhof TC. Cell biology and pathophysiology of α-synuclein. Cold Spring Harb Perspect Med. 2018;8:a024091.   DOI
152 Bonini NM, Giasson BI. Snaring the function of α-synuclein. Cell. 2005;123:359-61.   DOI
153 Bertotto LB, Catron TR, Tal T. Exploring interactions between xenobiotics, microbiota, and neurotoxicity in zebrafish. Neurotoxicology. 2020;76:235-44.   DOI
154 Shaafi S, Najmi S, Aliasgharpour H, Mahmoudi J, Sadigh-Etemad S, Farhoudi M, et al. The efficacy of the ketogenic diet on motor functions in Parkinson's disease: a rat model. Iran J Neurol. 2016;15:63-9.
155 Braak H, Braak E. Pathoanatomy of Parkinson's disease. J Neurol. 2000;247:II3-II10.   DOI
156 Braak H, Rub U, Gai WP, Del Tredici K. Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm. 2003;110:517-36.   DOI
157 Sager JJ, Bai Q, Burton EA. Transgenic zebrafish models of neurodegenerative diseases. Brain Struct Funct. 2010;214:285-302.   DOI
158 Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell. 2016;167:1469-80.e12.   DOI
159 Sargent D, Betemps D, Drouyer M, Verchere J, Gaillard D, Arsac JN, et al. Investigating the neuroprotective effect of AAV-mediated β-synuclein overexpression in a transgenic model of synucleinopathy. Sci Rep. 2018;8:17563.   DOI
160 Savica R, Boeve BF, Mielke MM. When do α-synucleinopathies start? An epidemiological timeline: a review. JAMA Neurol. 2018;75:503-9.   DOI
161 Northam C, LeMoine CMR. Metabolic regulation by the PGC1α and PGC-1β coactivators in larval zebrafish (Danio rerio). Comp Biochem Physiol A Mol Integr Physiol. 2019;234:60-7.   DOI
162 Musgrove RE, Horne J, Wilson R, King AE, Edwards LM, Dickson TC. The metabolomics of alpha-synuclein (SNCA) gene deletion and mutation in mouse brain. Metabolomics. 2014;10:114-22.   DOI
163 Najib NHM, Nies YH, Abd Halim SAS, Yahaya MF, Das S, Lim WL, et al. Modeling Parkinson's disease in zebrafish. CNS Neurol Disord Drug Targets. 2020;19:386-99.   DOI
164 NLM. SNCA - synuclein alpha. [Internet]. 2017 [cited 2021 Jun 21]. https://www.ncbi.nlm.nih.gov/kis/ortholog/6622/?scope=7776
165 Nuytemans K, Theuns J, Cruts M, Van Broeckhoven C. Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update. Hum Mutat. 2010;31:763-80.   DOI
166 O'Donnell KC, Lulla A, Stahl MC, Wheat ND, Bronstein JM, Sagasti A. Axon degeneration and PGC-1α-mediated protection in a zebrafish model of α-synuclein toxicity. Dis Model Mech. 2014;7:571-82.   DOI
167 O'Hara DM, Pawar G, Kalia SK, Kalia LV. LRRK2 and α-synuclein: distinct or synergistic players in Parkinson's disease? Front Neurosci. 2020;14:577.   DOI
168 Ohnesorge N, Heinl C, Lewejohann L. Current methods to investigate nociception and pain in zebrafish. Front Neurosci. 2021;15:632634.   DOI
169 Ohno M, Nikaido M, Horiuchi N, Kawakami K, Hatta K. The enteric nervous system in zebrafish larvae can regenerate via migration into the ablated area and proliferation of neural crest-derived cells. Development. 2021;148:dev195339.
170 Senior SL, Ninkina N, Deacon R, Bannerman D, Buchman VL, Cragg SJ, et al. Increased striatal dopamine release and hyperdopaminergic-like behaviour in mice lacking both alpha-synuclein and gamma-synuclein. Eur J Neurosci. 2008;27:947-57.   DOI
171 Shen T, Yue Y, He T, Huang C, Qu B, Lv W, et al. The association between the gut microbiota and Parkinson's disease, a meta-analysis. Front Aging Neurosci. 2021;13:636545.   DOI
172 Shepherd I, Eisen J. Development of the zebrafish enteric nervous system. Methods Cell Biol. 2011;101:143-60.   DOI
173 Shishido T, Nagano Y, Araki M, Kurashige T, Obayashi H, Nakamura T, et al. Synphilin-1 has neuroprotective effects on MPP+-induced Parkinson's disease model cells by inhibiting ROS production and apoptosis. Neurosci Lett. 2019;690:145-50.   DOI
174 Siddiqui IJ, Pervaiz N, Abbasi AA. The Parkinson disease gene SNCA: evolutionary and structural insights with pathological implication. Sci Rep. 2016;6:24475.   DOI
175 Specht CG, Schoepfer R. Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice. BMC Neurosci. 2001;2:11.   DOI
176 Bendor JT, Logan TP, Edwards RH. The function of α-synuclein. Neuron. 2013;79:1044-66.   DOI
177 Benner EJ, Banerjee R, Reynolds AD, Sherman S, Pisarev VM, Tsiperson V, et al. Nitrated α-synuclein immunity accelerates degeneration of nigral dopaminergic neurons. PLOS ONE. 2008;3:e1376.   DOI
178 Oueslati A, Ximerakis M, Vekrellis K. Protein transmission, seeding and degradation: key steps for α-synuclein prion-like propagation. Exp Neurobiol. 2014;23:324-36.   DOI
179 Olsson C, Holmberg A, Holmgren S. Development of enteric and vagal innervation of the zebrafish (Danio rerio) gut. J Comp Neurol. 2008;508:756-70.   DOI
180 Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J, et al. α-Synuclein shares physical and functional homology with 14-3-3 proteins. J Neurosci. 1999;19:5782-91.   DOI
181 Parichy DM, Elizondo MR, Mills MG, Gordon TN, Engeszer RE. Normal table of postembryonic zebrafish development: staging by externally visible anatomy of the living fish. Dev Dyn. 2009;238:2975-3015.   DOI
182 Park JY, Lansbury PT Jr. β-Synuclein inhibits formation of α-synuclein protofibrils: a possible therapeutic strategy against Parkinson's disease. Biochemistry. 2003;42:3696-700.   DOI
183 Parkinson J. An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci. 2002;14:223-36.   DOI
184 Periquet M, Fulga T, Myllykangas L, Schlossmacher MG, Feany MB. Aggregated α-synuclein mediates dopaminergic neurotoxicity in vivo. J Neurosci. 2007;27:3338-46.   DOI
185 Peters OM, Shelkovnikova T, Highley JR, Cooper-Knock J, Hortobagyi T, Troakes C, et al. Gamma-synuclein pathology in amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2015;2:29-37.   DOI
186 Pham LN, Kanther M, Semova I, Rawls JF. Methods for generating and colonizing gnotobiotic zebrafish. Nat Protoc. 2008;3:1862-75.   DOI
187 Pietrucci D, Teofani A, Unida V, Cerroni R, Biocca S, Stefani A, et al. Can gut microbiota be a good predictor for Parkinson's disease? A machine learning approach. Brain Sci. 2020;10:242.   DOI
188 Sun Z, Gitler AD. Discovery and characterization of three novel synuclein genes in zebrafish. Dev Dyn. 2008;237:2490-5.   DOI
189 Spillantini MG, Schmidt ML, Lee VMY, Trojanowski JQ, Jakes R, Goedert M. α-synuclein in Lewy bodies. Nature. 1997;388:839-40.   DOI
190 Stefanis L. α-Synuclein in Parkinson's disease. Cold Spring Harb Perspect Med. 2012;2:a009399.   DOI
191 Tanaka M, Kim YM, Lee G, Junn E, Iwatsubo T, Mouradian MM. Aggresomes formed by α-synuclein and synphilin-1 are cytoprotective. J Biol Chem. 2004;279:4625-31.   DOI
192 Rotshenker S. Wallerian degeneration: the innate-immune response to traumatic nerve injury. J Neuroinflammation. 2011;8:109.   DOI
193 Prabhudesai S, Sinha S, Attar A, Kotagiri A, Fitzmaurice AG, Lakshmanan R, et al. A novel "molecular tweezer" inhibitor of α-synuclein neurotoxicity in vitro and in vivo. Neurotherapeutics. 2012;9:464-76.   DOI
194 Provost E, Rhee J, Leach SD. Viral 2A peptides allow expression of multiple proteins from a single ORF in transgenic zebrafish embryos. Genesis. 2007;45:625-9.   DOI
195 Ravi V, Venkatesh B. The divergent genomes of teleosts. Annnu Rev Anim Biosci. 2018;6:47-68.   DOI
196 Sanchez E, Azcona LJ, Paisan-Ruiz C. Pla2g6 deficiency in zebrafish leads to dopaminergic cell death, axonal degeneration, increased beta-synuclein expression, and defects in brain functions and pathways. Mol Neurobiol. 2018;55:6734-54.   DOI
197 Sen S, West AB. The therapeutic potential of LRRK2 and α-synuclein in Parkinson's disease. Antioxid Redox Signal. 2009;11:2167-87.   DOI
198 Chavarria C, Souza JM. Oxidation and nitration of α-synuclein and their implications in neurodegenerative diseases. Arch Biochem Biophys. 2013;533:25-32.   DOI
199 Cansiz D, unal I, ustundag uV, Alturfan AA, Altinoz MA, Elmaci I, et al. Caprylic acid ameliorates rotenone induced inflammation and oxidative stress in the gut-brain axis in Zebrafish. Mol Biol Rep. 2021;48:5259-73.   DOI
200 Cantarero-Prieto D, Leon PL, Blazquez-Fernandez C, Juan PS, Cobo CS. The economic cost of dementia: a systematic review. Dementia. 2020;19:2637-57.   DOI
201 Tyson T, Steiner JA, Brundin P. Sorting out release, uptake and processing of alpha-synuclein during prion-like spread of pathology. J Neurochem. 2016;139:275-89.   DOI
202 Tannenbaum J, Bennett BT. Russell and Burch's 3Rs then and now: the need for clarity in definition and purpose. J Am Assoc Lab Anim Sci. 2015;54:120-32.
203 Thawkar BS, Kaur G. Zebrafish as a promising tool for modeling neurotoxin-induced Alzheimer's disease. Neurotox Res. 2021;39:949-65.   DOI
204 Touchman JW, Dehejia A, Chiba-Falek O, Cabin DE, Schwartz JR, Orrison BM, et al. Human and mouse alpha-synuclein genes: comparative genomic sequence analysis and identification of a novel gene regulatory element. Genome Res. 2001;11:78-86.   DOI
205 Ugalde CL, Finkelstein DI, Lawson VA, Hill AF. Pathogenic mechanisms of prion protein, amyloid-β and α-synuclein misfolding: the prion concept and neurotoxicity of protein oligomers. J Neurochem. 2016;139:162-80.   DOI
206 Unal I, Ustundag UV, Ates PS, Egilmezer G, Alturfan AA, Yigitbasi T, et al. Rotenone impairs oxidant/antioxidant balance both in brain and intestines in zebrafish. Int J Neurosci. 2019;129:363-8.   DOI
207 Shi L, Huang C, Luo Q, Xia Y, Liu H, Li L, et al. Pilot study: molecular risk factors for diagnosing sporadic Parkinson's disease based on gene expression in blood in MPTP-induced rhesus monkeys. Oncotarget. 2017;8:105606-14.   DOI
208 Cariulo C, Martufi P, Verani M, Azzollini L, Bruni G, Weiss A, et al. Phospho-S129 alpha-synuclein is present in human plasma but not in cerebrospinal fluid as determined by an ultrasensitive immunoassay. Front Neurosci. 2019;13:889.   DOI
209 Chen YC, Cheng CH, Chen GD, Hung CC, Yang CH, Hwang SPL, et al. Recapitulation of zebrafish sncga expression pattern and labeling the habenular complex in transgenic zebrafish using green fluorescent protein reporter gene. Dev Dyn. 2009b;238:746-54.   DOI
210 Cheng B, Yang X, An L, Gao B, Liu X, Liu S. Ketogenic diet protects dopaminergic neurons against 6-OHDA neurotoxicity via up-regulating glutathione in a rat model of Parkinson's disease. Brain Res. 2009;1286:25-31.   DOI
211 Slijkerman R, Goloborodko A, Broekman S, de Vrieze E, Hetterschijt L, Peters T, et al. Poor splice-site recognition in a humanized zebrafish knockin model for the recurrent deep-intronic c.7595-2144A>G mutation in USH2A. Zebrafish. 2018;15:597-609.   DOI
212 Spillantini MG, Divane A, Goedert M. Assignment of human alpha-synuclein (SNCA) and beta-synuclein (SNCB) genes to chromosomes 4q21 and 5q35. Genomics. 1995;27:379-81.   DOI
213 Stewart AM, Braubach O, Spitsbergen J, Gerlai R, Kalueff AV. Zebrafish models for translational neuroscience research: from tank to bedside. Trends Neurosci. 2014;37:264-78.   DOI
214 Varga M. The doctor of delayed publications: the remarkable life of George Streisinger (1927-1984). Zebrafish. 2018;15:314-9.   DOI
215 Vaccaro R, Toni M, Casini A, Vivacqua G, Yu S, D'este L, et al. Localization of α-synuclein in teleost central nervous system: immunohistochemical and Western blot evidence by 3D5 monoclonal antibody in the common carp, Cyprinus carpio. J Comp Neurol. 2015;523:1095-124.   DOI
216 Van Den Berge N, Ulusoy A. Animal models of brainfirst and body-first Parkinson's disease. Neurobiol Dis. 2022;163:105599.   DOI
217 Van Laar VS, Chen J, Zharikov AD, Bai Q, Di Maio R, Dukes AA, et al. α-Synuclein amplifies cytoplasmic peroxide flux and oxidative stress provoked by mitochondrial inhibitors in CNS dopaminergic neurons in vivo. Redox Biol. 2020;37:101695.   DOI
218 Vascellari S, Melis M, Palmas V, Pisanu S, Serra A, Perra D, et al. Clinical phenotypes of Parkinson's disease associate with distinct gut microbiota and metabolome enterotypes. Biomolecules. 2021;11:144.   DOI
219 Visanji NP, Brotchie JM, Kalia LV, Koprich JB, Tandon A, Watts JC, et al. α-Synuclein-based animal models of Parkinson's disease: challenges and opportunities in a new era. Trends Neurosci. 2016;39:750-62.   DOI
220 Wang Y, Liu W, Yang J, Wang F, Sima Y, Zhong Z, et al. Parkinson's disease-like motor and non-motor symptoms in rotenone-treated zebrafish. Neurotoxicology. 2017;58:103-9.   DOI
221 Wang YC, Feng GY, Xia QJ, Hu Y, Xu Y, Xiong L, et al. Knockdown of α-synuclein in cerebral cortex improves neural behavior associated with apoptotic inhibition and neurotrophin expression in spinal cord transected rats. Apoptosis. 2016;21:404-20.   DOI
222 Uemura O, Okada Y, Ando H, Guedj M, Higashijima S, Shimazaki T, et al. Comparative functional genomics revealed conservation and diversification of three enhancers of the isl1 gene for motor and sensory neuron-specific expression. Dev Biol. 2005;278:587-606.   DOI
223 Tagliaferro P, Burke RE. Retrograde axonal degeneration in Parkinson disease. J Parkinsons Dis. 2016;6:1-15.   DOI
224 Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, et al. Rotenone, paraquat, and Parkinson's disease. Environ Health Perspect. 2011;119:866-72.   DOI
225 Toni M, Cioni C. Fish synucleins: an update. Mar Drugs. 2015;13:6665-86.   DOI
226 Vargas KJ, Colosi PL, Girardi E, Park JM, Chandra SS. α-Synuclein facilitates clathrin assembly in synaptic vesicle endocytosis [Internal]. bioRxiv. 2021 [cited 2022 Jan 10]. https://doi.org/10.1101/2020.04.29.069344   DOI
227 Vaz RL, Outeiro TF, Ferreira JJ. Zebrafish as an animal model for drug discovery in Parkinson's disease and other movement disorders: a systematic review. Front Neurol. 2018;9:347.   DOI
228 Wakabayashi K, Tanji K, Mori F, Takahashi H. The Lewy body in Parkinson's disease: molecules implicated in the formation and degradation of α-synuclein aggregates. Neuropathology. 2007;27:494-506.   DOI
229 Weston LJ, Cook ZT, Stackhouse TL, Sal MK, Schultz BI, Tobias ZJC, et al. In vivo aggregation of presynaptic alpha-synuclein is not influenced by its phosphorylation at serine-129. Neurobiol Dis. 2021;152:105291.   DOI
230 Xi Y, Yu M, Godoy R, Hatch G, Poitras L, Ekker M. Transgenic zebrafish expressing green fluorescent protein in dopaminergic neurons of the ventral diencephalon. Dev Dyn. 2011;240:2539-47.   DOI
231 Xu Y, Li K, Qin W, Zhu B, Zhou Z, Shi J, et al. Unraveling the role of hydrogen peroxide in α-synuclein aggregation using an ultrasensitive nanoplasmonic probe. Anal Chem. 2015;87:1968-73.   DOI
232 Barbereau C, Cubedo N, Maurice T, Rossel M. Zebrafish models to study new pathways in tauopathies. Int J Mol Sci. 2021;22:4626.   DOI
233 Barnhill LM, Murata H, Bronstein JM. Studying the pathophysiology of Parkinson's disease using zebrafish. Biomedicines. 2020;8:197.   DOI
234 Bedell VM, Westcot SE, Ekker SC. Lessons from morpholino-based screening in zebrafish. Brief Funct Genomics. 2011;10:181-8.   DOI
235 White RM, Sessa A, Burke C, Bowman T, LeBlanc J, Ceol C, et al. Transparent adult zebrafish as a tool for in vivo transplantation analysis. Cell Stem Cell. 2008;2:183-9.   DOI
236 Wyatt C, Bartoszek EM, Yaksi E. Methods for studying the zebrafish brain: past, present and future. Eur J Neurosci. 2015;42:1746-63.   DOI
237 Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, Ampuero I, et al. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol. 2004;55:164-73.   DOI
238 Zhang Z, Peng Q, Huo D, Jiang S, Ma C, Chang H, et al. Melatonin regulates the neurotransmitter secretion disorder induced by caffeine through the microbiota-gut-brain axis in zebrafish (Danio rerio). Front Cell Dev Biol. 2021;9:678190.   DOI
239 Zou J, Fan YJ, Meng YQ, Xu H, Fan J. An exploratory analysis of γ-synuclein expression in endometrioid endometrial cancer. BMJ Open. 2012;2:e000611.   DOI
240 Yang X, Xu S, Qian Y, He X, Chen S, Xiao Q. Hypermethylation of the gene coding for PGC-1α in peripheral blood leukocytes of patients with Parkinson's disease. Front Neurosci. 2020;14:97.   DOI
241 Chu Y, Kordower JH. Age-associated increases of alpha-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: is this the target for Parkinson's disease? Neurobiol Dis. 2007;25:134-49.   DOI
242 Choi TY, Choi TI, Lee YR, Choe SK, Kim CH. Zebrafish as an animal model for biomedical research. Exp Mol Med. 2021;53:310-7.   DOI
243 Choong CJ, Say YH. Neuroprotection of α-synuclein under acute and chronic rotenone and maneb treatment is abolished by its familial Parkinson's disease mutations A30P, A53T and E46K. Neurotoxicology. 2011;32:857-63.   DOI
244 Chou AP, Maidment N, Klintenberg R, Casida JE, Li S, Fitzmaurice AG, et al. Ziram causes dopaminergic cell damage by inhibiting E1 ligase of the proteasome. J Biol Chem. 2008;283:34696-703.   DOI
245 Liu J, Li T, Thomas JM, Pei Z, Jiang H, Engelender S, et al. Synphilin-1 attenuates mutant LRRK2-induced neurodegeneration in Parkinson's disease models. Hum Mol Genet. 2016;25:672-80.   DOI
246 Li X, Dang J, Li Y, Wang L, Li N, Liu K, et al. Developmental neurotoxicity fingerprint of silica nanoparticles at environmentally relevant level on larval zebrafish using a neurobehavioral-phenomics-based biological warning method. Sci Total Environ. 2021;752:141878.   DOI
247 Lingor P, Koch JC, Tonges L, Bahr M. Axonal degeneration as a therapeutic target in the CNS. Cell Tissue Res. 2012;349:289-311.   DOI
248 Linnertz C, Saucier L, Ge D, Cronin KD, Burke JR, Browndyke JN, et al. Genetic regulation of α-synuclein mRNA expression in various human brain tissues. PLOS ONE. 2009;4:e7480.   DOI
249 Zheng B, Liao Z, Locascio JJ, Lesniak KA, Roderick SS, Watt ML, et al. PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease. Sci Transl Med. 2010;2:52ra73.   DOI
250 Yurtsever I, ustundag uV, unal I, Ates PS, Emekli-Alturfan E. Rifampicin decreases neuroinflammation to maintain mitochondrial function and calcium homeostasis in rotenone-treated zebrafish. Drug Chem Toxicol. 2020:1-8.
251 Conforti L, Gilley J, Coleman MP. Wallerian degeneration: an emerging axon death pathway linking injury and disease. Nat Rev Neurosci. 2014;15:394-409.   DOI
252 Conway KA, Harper JD, Lansbury PT. Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nat Med. 1998;4:1318-20.   DOI