Skip to main content
SpringerLink
Log in

Parkinson’s Disease Model

  • Chapter
  • First Online:
Drosophila Models for Human Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1076))

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. It is known that there are many factors, either genetic or environmental factors, involved in PD, but the mechanism of PD is still not fully understood. Several animal models have been established to study the mechanisms of PD. Among these models, Drosophila melanogaster has been utilized as a valuable model to get insight into important features of PD. Drosophila melanogaster possesses a well-developed dopaminergic (DA) neuron system which is known to play an important role in PD pathogenesis. The well understanding of DA neurons from early larval through adult stage makes Drosophila as a powerful model for investigating the progressive neurodegeneration in PD. Besides, the short life cycle of Drosophila melanogaster serves an advantage in studying epidemiological features of PD. Most of PD symptoms can be mimicked in Drosophila model such as progressive impairment in locomotion, DA neuron degeneration, and some other non-motor symptoms. The Drosophila models of PD, therefore, show a great potential in application for PD genetic and drug screening.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Adams MD, et al. The genome sequence of Drosophila melanogaster. Science. 2000;287(5461):2185–95.

    Article  PubMed  Google Scholar 

  • Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R. Mutations in the glucocerebrosidase gene and Parkinson’s disease in Ashkenazi Jews. N Engl J Med. 2004;351(19):1972–7.

    Article  PubMed  CAS  Google Scholar 

  • Alberio T, Lopiano L, Fasano M. Cellular models to investigate biochemical pathways in Parkinson’s disease. FEBS J. 2012;279(7):1146–55.

    Article  PubMed  CAS  Google Scholar 

  • Ameel KN, et al. Paraquat induced dopaminergic neuronal loss in Drosophila melanogaster. FASEB J. 2007;21(6):LB65.

    Google Scholar 

  • Angeles DC, et al. Antioxidants inhibit neuronal toxicity in Parkinson’s disease-linked LRRK2. Ann Clin Transl Neurol. 2016;3(4):288–94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Annesi G, et al. DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex. Ann Neurol. 2005;58(5):803–7.

    Article  PubMed  CAS  Google Scholar 

  • Arranz AM, et al. LRRK2 functions in synaptic vesicle endocytosis through a kinase-dependent mechanism. J Cell Sci. 2015;128(3):541–52.

    Article  PubMed  CAS  Google Scholar 

  • Berry JA, et al. Dopamine is required for learning and forgetting in Drosophila. Neuron. 2012;74(3):530–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Blanco J, et al. Orthodenticle is necessary for survival of a cluster of clonally related dopaminergic neurons in the Drosophila larval and adult brain. Neural Dev. 2011;6:34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Blesa J, et al. The use of nonhuman primate models to understand processes in Parkinson’s disease. J Neural Transm (Vienna). 2017;125(3):325-33.

    Article  PubMed  CAS  Google Scholar 

  • Bonifati V, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science. 2003;299(5604):256–9.

    Article  PubMed  CAS  Google Scholar 

  • Botella JA, Bayersdorfer F, Schneuwly S. Superoxide dismutase overexpression protects dopaminergic neurons in a Drosophila model of Parkinson’s disease. Neurobiol Dis. 2008;30(1):65–73.

    Article  PubMed  CAS  Google Scholar 

  • Budnik V, White K. Catecholamine-containing neurons in Drosophila melanogaster: distribution and development. J Comp Neurol. 1988;268(3):400–13.

    Article  PubMed  CAS  Google Scholar 

  • Butler EK, et al. The mitochondrial chaperone protein TRAP1 mitigates alpha-Synuclein toxicity. PLoS Genet. 2012;8(2):e1002488.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Byers B, Lee HL, Reijo Pera R. Modeling Parkinson’s disease using induced pluripotent stem cells. Curr Neurol Neurosci Rep. 2012;12(3):237–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Celardo I, et al. Mitofusin-mediated ER stress triggers neurodegeneration in pink1/parkin models of Parkinson’s disease. Cell Death Dis. 2016;7(6):e2271.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen L, Feany MB. Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat Neurosci. 2005;8(5):657–63.

    Article  PubMed  CAS  Google Scholar 

  • Chen X, et al. Using C. elegans to discover therapeutic compounds for ageing-associated neurodegenerative diseases. Chem Cent J. 2015;9:65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Clark IE, et al. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature. 2006;441(7097):1162–6.

    Article  PubMed  CAS  Google Scholar 

  • Coulom H, Birman S. Chronic exposure to rotenone models sporadic Parkinson’s disease in Drosophila melanogaster. J Neurosci. 2004;24(48):10993–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron. 2003;39(6):889–909.

    Article  PubMed  CAS  Google Scholar 

  • Dawson TM, Ko HS, Dawson VL. Genetic animal models of Parkinson’s disease. Neuron. 2010;66(5):646–61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • de Lau LM, Breteler MM. Epidemiology of Parkinson’s disease. Lancet Neurol. 2006;5(6):525–35.

    Article  PubMed  Google Scholar 

  • Deng H, et al. The Parkinson’s disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci U S A. 2008;105(38):14503–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dexter DT, Jenner P. Parkinson disease: from pathology to molecular disease mechanisms. Free Radic Biol Med. 2013;62:132–44.

    Article  PubMed  CAS  Google Scholar 

  • Di Fonzo A, et al. A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson’s disease. Lancet. 2005;365(9457):412–5.

    Article  PubMed  CAS  Google Scholar 

  • Dodson MW, et al. Roles of the Drosophila LRRK2 homolog in Rab7-dependent lysosomal positioning. Hum Mol Genet. 2012;21(6):1350–63.

    Article  PubMed  CAS  Google Scholar 

  • Dodson MW, et al. Novel ethyl methanesulfonate (EMS)-induced null alleles of the Drosophila homolog of LRRK2 reveal a crucial role in endolysosomal functions and autophagy in vivo. Dis Model Mech. 2014;7(12):1351–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ebrahimi-Fakhari D, Wahlster L, McLean PJ. Protein degradation pathways in parkinson’s disease – curse or blessing. Acta Neuropathol. 2012;124(2):153–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Esposito G, et al. Aconitase causes iron toxicity in Drosophila pink1 mutants. PLoS Genet. 2013;9(4):e1003478.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Exner N, et al. Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci. 2007;27(45):12413–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fahn S, Sulzer D. Neurodegeneration and neuroprotection in Parkinson disease. NeuroRx. 2004;1(1):139–54.

    Article  PubMed  PubMed Central  Google Scholar 

  • Falkenburger BH, Schulz JB. Limitations of cellular models in Parkinson’s disease research. J Neural Transm Suppl. 2006;70:261–8.

    Article  CAS  Google Scholar 

  • Falkenburger BH, Saridaki T, Dinter E. Cellular models for Parkinson’s disease. J Neurochem. 2016;139(Suppl 1):121–30.

    Article  PubMed  CAS  Google Scholar 

  • Feany MB, Bender WW. A Drosophila model of Parkinson’s disease. Nature. 2000;404(6776):394–8.

    Article  PubMed  CAS  Google Scholar 

  • Fernandes C, Rao Y. Genome-wide screen for modifiers of Parkinson’s disease genes in Drosophila. Mol Brain. 2011;4:17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Forno LS. Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol. 1996;55(3):259–72.

    Article  PubMed  CAS  Google Scholar 

  • Gautier CA, Kitada T, Shen J. Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc Natl Acad Sci U S A. 2008;105(32):11364–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gegg ME, et al. Silencing of PINK1 expression affects mitochondrial DNA and oxidative phosphorylation in dopaminergic cells. PLoS One. 2009;4(3):e4756.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • German DC, et al. Midbrain dopaminergic cell loss in Parkinson’s disease: computer visualization. Ann Neurol. 1989;26(4):507–14.

    Article  PubMed  CAS  Google Scholar 

  • Giacomotto J, Ségalat L. High-throughput screening and small animal models, where are we? Br J Pharmacol. 2010;160(2):204–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Goldman JG, Postuma R. Premotor and nonmotor features of Parkinson’s disease. Curr Opin Neurol. 2014;27(4):434–41.

    Article  PubMed  PubMed Central  Google Scholar 

  • Greene JC, et al. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci U S A. 2003;100(7):4078–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Greene JC, et al. Genetic and genomic studies of Drosophila parkin mutants implicate oxidative stress and innate immune responses in pathogenesis. Hum Mol Genet. 2005;14(6):799–811.

    Article  PubMed  CAS  Google Scholar 

  • Grunewald A, et al. Mutant Parkin impairs mitochondrial function and morphology in human fibroblasts. PLoS One. 2010;5(9):e12962.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guo M. What have we learned from Drosophila models of Parkinson’s disease? Prog Brain Res. 2010;184:3–16.

    PubMed  CAS  Google Scholar 

  • Hao L-Y, Giasson BI, Bonini NM. DJ-1 is critical for mitochondrial function and rescues PINK1 loss of function. Proc Natl Acad Sci U S A. 2010;107(21):9747–52.

    Article  PubMed  PubMed Central  Google Scholar 

  • Harrington AJ, et al. C. elegans as a model organism to investigate molecular pathways involved with Parkinson’s disease. Dev Dyn. 2010;239(5):1282–95.

    PubMed  CAS  Google Scholar 

  • Hedrich K, et al. Clinical spectrum of homozygous and heterozygous PINK1 mutations in a large German family with Parkinson disease: role of a single hit? Arch Neurol. 2006;63(6):833–8.

    Article  PubMed  Google Scholar 

  • Hindle S, et al. Dopaminergic expression of the Parkinsonian gene LRRK2-G2019S leads to non-autonomous visual neurodegeneration, accelerated by increased neural demands for energy. Hum Mol Genet. 2013;22(11):2129–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hisahara S, Shimohama S. Toxin-induced and genetic animal models of Parkinson’s disease. Parkinson’s Dis. 2011;2011: 951709.

    Article  CAS  Google Scholar 

  • Hoenicka J, et al. Molecular findings in familial Parkinson disease in Spain. Arch Neurol. 2002;59(6):966–70.

    Article  PubMed  Google Scholar 

  • Hosamani R. Acute exposure of Drosophila melanogaster to paraquat causes oxidative stress and mitochondrial dysfunction. Arch Insect Biochem Physiol. 2013;83(1):25–40.

    Article  PubMed  CAS  Google Scholar 

  • Hosamani R, Ramesh SR, Muralidhara. Attenuation of rotenone-induced mitochondrial oxidative damage and neurotoxicty in Drosophila melanogaster supplemented with creatine. Neurochem Res. 2010;35(9):1402–12.

    Article  PubMed  CAS  Google Scholar 

  • Hwang S, et al. Drosophila DJ-1 decreases neural sensitivity to stress by negatively regulating Daxx-like protein through dFOXO. PLoS Genet. 2013;9(4):e1003412.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hwang RD, et al. The neuroprotective effect of human uncoupling protein 2 (hUCP2) requires cAMP-dependent protein kinase in a toxin model of Parkinson’s disease. Neurobiol Dis. 2014;69:180–91.

    Article  PubMed  CAS  Google Scholar 

  • Imai Y, et al. Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila. EMBO J. 2008;27(18):2432–43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Islam MS, et al. Human R1441C LRRK2 regulates the synaptic vesicle proteome and phosphoproteome in a Drosophila model of Parkinson’s disease. Hum Mol Genet. 2016;25(24):5365–82.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Jagmag SA, et al. Evaluation of models of Parkinson’s disease. Front Neurosci. 2016;9:503.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79(4):368–76.

    Article  PubMed  CAS  Google Scholar 

  • Jennings BH. Drosophila – a versatile model in biology & medicine. Mater Today. 2011;14(5):190–5.

    Article  Google Scholar 

  • Julienne H, et al. Drosophila PINK1 and parkin loss-of-function mutants display a range of non-motor Parkinson’s disease phenotypes. Neurobiol Dis. 2017;104:15–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kitada T, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392(6676):605–8.

    Article  PubMed  CAS  Google Scholar 

  • Klemann CJHM, et al. Integrated molecular landscape of Parkinson’s disease. NPJ Parkinson’s Dis. 2017;3:14.

    Article  CAS  Google Scholar 

  • Koprich JB, et al. Towards a non-human primate model of alpha-synucleinopathy for development of therapeutics for Parkinson’s disease: optimization of AAV1/2 delivery parameters to drive sustained expression of alpha synuclein and dopaminergic degeneration in macaque. PLoS One. 2016;11(11):e0167235.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lakso M, et al. Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein. J Neurochem. 2003;86(1):165–72.

    Article  PubMed  CAS  Google Scholar 

  • Lavara-Culebras E, Paricio N. Drosophila DJ-1 mutants are sensitive to oxidative stress and show reduced lifespan and motor deficits. Gene. 2007;400(1–2):158–65.

    Article  PubMed  CAS  Google Scholar 

  • Lawal HO, et al. Drosophila modifier screens to identify novel neuropsychiatric drugs including aminergic agents for the possible treatment of Parkinson’s disease and depression. Mol Psychiatry. 2014;19(2):235–42.

    Article  PubMed  CAS  Google Scholar 

  • Le Bourg E, Lints FA. Hypergravity and aging in Drosophila melanogaster. 4. Climbing activity. Gerontology. 1992;38(1–2):59–64.

    Article  PubMed  Google Scholar 

  • Lee YC, Hsu SD. Familial mutations and post-translational modifications of UCH-L1 in Parkinson’s disease and neurodegenerative disorders. Curr Protein Pept Sci. 2017;18(7):733–45.

    Article  PubMed  CAS  Google Scholar 

  • Lee SB, et al. Loss of LRRK2/PARK8 induces degeneration of dopaminergic neurons in Drosophila. Biochem Biophys Res Commun. 2007;358(2):534–9.

    Article  PubMed  CAS  Google Scholar 

  • Lee S, et al. LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction. J Neurosci. 2010;30(50):16959–69.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Leroy E, et al. The ubiquitin pathway in Parkinson’s disease. Nature. 1998;395(6701):451–2.

    Article  PubMed  CAS  Google Scholar 

  • Li J, Le W. Modeling neurodegenerative diseases in Caenorhabditis elegans. Exp Neurol. 2013;250:94–103.

    Article  PubMed  CAS  Google Scholar 

  • Lim K-L, Ng C-H. Genetic models of Parkinson disease. Biochim Biophys Acta (BBA) Mol Basis Dis. 2009;1792(7):604–15.

    Article  CAS  Google Scholar 

  • Linhart R, et al. Vacuolar protein sorting 35 (Vps35) rescues locomotor deficits and shortened lifespan in Drosophila expressing a Parkinson’s disease mutant of leucine-rich repeat kinase 2 (LRRK2). Mol Neurodegener. 2014;9:23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu Y, et al. The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility. Cell. 2002;111(2):209–18.

    Article  PubMed  CAS  Google Scholar 

  • Liu Z, et al. A Drosophila model for LRRK2-linked parkinsonism. Proc Natl Acad Sci U S A. 2008;105(7):2693–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Malagelada C, Greene LA. Chapter 29 – PC12 cells as a model for Parkinson’s disease research. In: Parkinson’s disease. San Diego: Academic; 2008. p. 375–87.

    Google Scholar 

  • Mao Z, Davis RL. Eight different types of dopaminergic neurons innervate the Drosophila mushroom body neuropil: anatomical and physiological heterogeneity. Front Neural Circuits. 2009;3:5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Maor G, et al. Unfolded protein response in Gaucher disease: from human to Drosophila. Orphanet J Rare Dis. 2013;8:140.

    Article  PubMed  PubMed Central  Google Scholar 

  • Maor G, et al. The contribution of mutant GBA to the development of Parkinson disease in Drosophila. Hum Mol Genet. 2016;25(13):2712–27.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Martinez-Morales PL, Liste I. Stem cells as in vitro model of Parkinson’s disease. Stem Cells Int. 2012;2012:980941.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Matsui H. Dopamine system, cerebellum, and nucleus ruber in fish and mammals. Develop Growth Differ. 2017;59(4):219–27.

    Article  CAS  Google Scholar 

  • Matsui H, Takahashi R. Parkinson’s disease pathogenesis from the viewpoint of small fish models. J Neural Transm (Vienna). 2017. https://doi.org/10.1007/s00702-017-1772-1

  • Matsui H, Gavinio R, Takahashi R. Medaka fish Parkinson’s disease model. Exp Neurobiol. 2012;21(3):94–100.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mayes-Burnett DM. Central nervous system drugs, pharmacology for nurses. Burlington: Jones & Bartlett Learning; 2016. p. 91–130.

    Google Scholar 

  • Medina-Leendertz S, et al. Longterm melatonin administration alleviates paraquat mediated oxidative stress in Drosophila melanogaster. Investig Clin. 2014;55(4):352–64.

    Google Scholar 

  • Mehdi SH, Qamar A. Paraquat-induced ultrastructural changes and DNA damage in the nervous system is mediated via oxidative-stress-induced cytotoxicity in Drosophila melanogaster. Toxicol Sci. 2013;134(2):355–65.

    Article  PubMed  CAS  Google Scholar 

  • Meulener M, et al. Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson’s disease. Curr Biol. 2005;15(17):1572–7.

    Article  PubMed  CAS  Google Scholar 

  • Min VA, Condron BG. An assay of behavioral plasticity in Drosophila larvae. J Neurosci Methods. 2005;145(1–2):63–72.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mizuno H, et al. α-Synuclein transgenic Drosophila as a model of Parkinson’s disease and related synucleinopathies. Parkinson’s Dis. 2011;2011:212706.

    Google Scholar 

  • Montgomery EB Jr. Heavy metals and the etiology of Parkinson’s disease and other movement disorders. Toxicology. 1995;97(1–3):3–9.

    Article  PubMed  CAS  Google Scholar 

  • Moon HE, Paek SH. Mitochondrial dysfunction in Parkinson’s disease. Exp Neurobiol. 2015;24(2):103–16.

    Article  PubMed  PubMed Central  Google Scholar 

  • Muftuoglu M, et al. Mitochondrial complex I and IV activities in leukocytes from patients with parkin mutations. Mov Disord. 2004;19(5):544–8.

    Article  PubMed  Google Scholar 

  • Nassel DR, Elekes K. Aminergic neurons in the brain of blowflies and Drosophila: dopamine- and tyrosine hydroxylase-immunoreactive neurons and their relationship with putative histaminergic neurons. Cell Tissue Res. 1992;267(1):147–67.

    Article  PubMed  CAS  Google Scholar 

  • Navarro JA, et al. Analysis of dopaminergic neuronal dysfunction in genetic and toxin-induced models of Parkinson’s disease in Drosophila. J Neurochem. 2014;131(3):369–82.

    Article  PubMed  CAS  Google Scholar 

  • Nussbaum RL, Polymeropoulos MH. Genetics of Parkinson’s disease. Hum Mol Genet. 1997;6(10):1687–91.

    Article  PubMed  CAS  Google Scholar 

  • Paisán-Ruız C, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron. 2004;44(4):595–600.

    Article  PubMed  Google Scholar 

  • Palacino JJ, et al. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem. 2004;279(18):18614–22.

    Article  PubMed  CAS  Google Scholar 

  • Park J, et al. Drosophila DJ-1 mutants show oxidative stress-sensitive locomotive dysfunction. Gene. 2005;361:133–9.

    Article  PubMed  CAS  Google Scholar 

  • Park J, et al. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature. 2006;441(7097):1157–61.

    Article  PubMed  CAS  Google Scholar 

  • Park J, Lee G, Chung J. The PINK1-Parkin pathway is involved in the regulation of mitochondrial remodeling process. Biochem Biophys Res Commun. 2009;378(3):518–23.

    Article  PubMed  CAS  Google Scholar 

  • Perez-Lloret S, Barrantes FJ. Deficits in cholinergic neurotransmission and their clinical correlates in Parkinson’s disease. NPJ Parkinsons Dis. 2016;2:16001.

    Article  PubMed  PubMed Central  Google Scholar 

  • Periquet M, et al. Aggregated alpha-synuclein mediates dopaminergic neurotoxicity in vivo. J Neurosci. 2007;27(12):3338–46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pesah Y, et al. Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress. Development. 2004;131(9):2183–94.

    Article  PubMed  CAS  Google Scholar 

  • Pezzoli G, Cereda E. Exposure to pesticides or solvents and risk of Parkinson disease. Neurology. 2013;80(22):2035–41.

    Article  PubMed  CAS  Google Scholar 

  • Polymeropoulos MH, et al. Mutation in the α-synuclein gene identified in families with Parkinson’s disease. Science. 1997;276(5321):2045–7.

    Article  PubMed  CAS  Google Scholar 

  • Poole AC, et al. The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A. 2008;105(5):1638–43.

    Article  PubMed  PubMed Central  Google Scholar 

  • Poole AC, et al. The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/Parkin pathway. PLoS One. 2010;5(4):e10054.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Porras G, Li Q, Bezard E. Modeling Parkinson’s disease in primates: the MPTP model. Cold Spring Harb Perspect Med. 2012;2(3):a009308.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Riemensperger T, et al. A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease. Cell Rep. 2013;5(4):952–60.

    Article  PubMed  CAS  Google Scholar 

  • Ross CA, Smith WW. Gene-environment interactions in Parkinson’s disease. Parkinsonism Relat Disord. 2007;13(Suppl 3):S309–15.

    Article  PubMed  Google Scholar 

  • Saha S, et al. LRRK2 modulates vulnerability to mitochondrial dysfunction in Caenorhabditis elegans. J Neurosci. 2009;29(29):9210–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sang TK, et al. A Drosophila model of mutant human parkin-induced toxicity demonstrates selective loss of dopaminergic neurons and dependence on cellular dopamine. J Neurosci. 2007;27(5):981–92.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sanz FJ, et al. Identification of potential therapeutic compounds for Parkinson’s disease using Drosophila and human cell models. Free Radic Biol Med. 2017;108:683–91.

    Article  PubMed  CAS  Google Scholar 

  • Scherzer CR, et al. Gene expression changes presage neurodegeneration in a Drosophila model of Parkinson’s disease. Hum Mol Genet. 2003;12(19):2457–66.

    Article  PubMed  CAS  Google Scholar 

  • Schule B, Pera RA, Langston JW. Can cellular models revolutionize drug discovery in Parkinson’s disease? Biochim Biophys Acta. 2009;1792(11):1043–51.

    Article  PubMed  CAS  Google Scholar 

  • Seidel K, et al. First appraisal of brain pathology owing to A30P mutant alpha-synuclein. Ann Neurol. 2010;67(5):684–9.

    PubMed  CAS  Google Scholar 

  • Selcho M, et al. The role of dopamine in Drosophila larval classical olfactory conditioning. PLoS One. 2009;4(6):e5897.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shadrina MI, Slominsky PA, Limborska SA. Molecular mechanisms of pathogenesis of Parkinson’s disease. Int Rev Cell Mol Biol. 2010;281:229–66.

    Article  PubMed  CAS  Google Scholar 

  • Shukla AK, et al. Metabolomic analysis provides insights on Paraquat-induced Parkinson-like symptoms in Drosophila melanogaster. Mol Neurobiol. 2016;53(1):254–69.

    Article  PubMed  CAS  Google Scholar 

  • Sidransky E, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease. N Engl J Med. 2009;361(17):1651–61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sulston J, Dew M, Brenner S. Dopaminergic neurons in the nematode Caenorhabditis elegans. J Comp Neurol. 1975;163(2):215–26.

    Article  PubMed  CAS  Google Scholar 

  • Suzuki T, et al. Expression of human Gaucher disease gene GBA generates neurodevelopmental defects and ER stress in Drosophila eye. PLoS One. 2013;8(8):e69147.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Takahashi R, et al. Phenolic compounds prevent the oligomerization of α-synuclein and reduce synaptic toxicity. J Neurochem. 2015;134(5):943–55.

    Article  PubMed  CAS  Google Scholar 

  • Tan JM, Wong ES, Lim KL. Protein misfolding and aggregation in Parkinson’s disease. Antioxid Redox Signal. 2009;11(9):2119–34.

    Article  PubMed  CAS  Google Scholar 

  • Tanaka A, et al. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol. 2010;191(7):1367–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thomas B, Beal MF. Parkinson’s disease. Hum Mol Genet. 2007;16(R2):R183–94.

    Article  PubMed  CAS  Google Scholar 

  • Tieu K. A guide to neurotoxic animal models of Parkinson’s disease. Cold Spring Harb Perspect Med. 2011;1(1):a009316.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Trimmer PA, Bennett JP. The cybrid model of sporadic Parkinson’s disease. Exp Neurol. 2009;218(2):320–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Trinh K, et al. Induction of the phase II detoxification pathway suppresses neuron loss in Drosophila models of Parkinson’s disease. J Neurosci. 2008;28(2):465–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ueno T, et al. Identification of a dopamine pathway that regulates sleep and arousal in Drosophila. Nat Neurosci. 2012;15(11):1516–23.

    Article  PubMed  CAS  Google Scholar 

  • Valente EM, et al. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science. 2004;304(5674):1158–60.

    Article  PubMed  CAS  Google Scholar 

  • Vartiainen S, et al. Identification of gene expression changes in transgenic C. elegans overexpressing human alpha-synuclein. Neurobiol Dis. 2006;22(3):477–86.

    Article  PubMed  CAS  Google Scholar 

  • Venderova K, et al. Leucine-rich repeat kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson’s disease. Hum Mol Genet. 2009;18(22):4390–404.

    Article  PubMed  CAS  Google Scholar 

  • Vernooy SY, et al. Cell death regulation in Drosophila: conservation of mechanism and unique insights. J Cell Biol. 2000;150(2):F69–76.

    Article  PubMed  CAS  Google Scholar 

  • Vincow ES, et al. The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo. Proc Natl Acad Sci U S A. 2013;110(16):6400–5.

    Article  PubMed  PubMed Central  Google Scholar 

  • Vingill S, Connor-Robson N, Wade-Martins R. Are rodent models of Parkinson’s disease behaving as they should? Behav Brain Res. 2017. https://doi.org/10.1016/j.bbr.2017.10.021

  • Wang D, et al. Dispensable role of Drosophila ortholog of LRRK2 kinase activity in survival of dopaminergic neurons. Mol Neurodegener. 2008;3:3–3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Whitworth AJ. Drosophila models of Parkinson’s disease. Adv Genet. 2011;73:1–50.

    PubMed  CAS  Google Scholar 

  • Whitworth AJ, et al. Increased glutathione S-transferase activity rescues dopaminergic neuron loss in a Drosophila model of Parkinson’s disease. Proc Natl Acad Sci U S A. 2005;102(22):8024–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Whitworth AJ, Wes PD, Pallanck LJ. Drosophila models pioneer a new approach to drug discovery for Parkinson’s disease. Drug Discov Today. 2006;11(3–4):119–26.

    Article  PubMed  CAS  Google Scholar 

  • Xi Y, Noble S, Ekker M. Modeling neurodegeneration in Zebrafish. Curr Neurol Neurosci Rep. 2011;11(3):274–82.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xicoy H, Wieringa B, Martens GJM. The SH-SY5Y cell line in Parkinson’s disease research: a systematic review. Mol Neurodegener. 2017;12:10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yang Y, et al. Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signaling. Proc Natl Acad Sci U S A. 2005;102(38):13670–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yang Y, et al. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc Natl Acad Sci U S A. 2006;103(28):10793–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yang Y, et al. Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc Natl Acad Sci U S A. 2008;105(19):7070–5.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang XM, Yin M, Zhang MH. Cell-based assays for Parkinson’s disease using differentiated human LUHMES cells. Acta Pharmacol Sin. 2014;35(7):945–56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang Y, et al. Rescue of Pink1 deficiency by stress-dependent activation of autophagy. Cell Chem Biol. 2017;24(4):471–480.e4.

    Article  PubMed  CAS  Google Scholar 

  • Zimprich A, et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004;44(4):601–7.

    Article  PubMed  CAS  Google Scholar 

  • Ziviani E, Tao RN, Whitworth AJ. Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci U S A. 2010;107(11):5018–23.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Science, Vietnam National University, Ho Chi Minh City, Vietnam

    Vuu My Dung & Dang Thi Phuong Thao

Authors
  1. Vuu My Dung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dang Thi Phuong Thao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dang Thi Phuong Thao .

Editor information

Editors and Affiliations

  1. Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan

    Masamitsu Yamaguchi

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dung, V.M., Thao, D.T.P. (2018). Parkinson’s Disease Model. In: Yamaguchi, M. (eds) Drosophila Models for Human Diseases. Advances in Experimental Medicine and Biology, vol 1076. Springer, Singapore. https://doi.org/10.1007/978-981-13-0529-0_4

Download citation

Publish with us

Policies and ethics

Search

Navigation