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Modeling of Human Parkinson’s Disease in Fly

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Insights into Human Neurodegeneration: Lessons Learnt from Drosophila

Abstract

Years of in-depth research have contributed substantially to the understanding of the pathophysiology of Parkinson’s diseases (PD). However, many crucial questions related to the etiology of the disease remain unanswered, which compelled the need for developing more realistic and genetically malleable model systems for modeling the precise neuropathology of the disease in vivo.

Ever-expanding genetic toolkit and conservation of implicated signaling pathways and neurological properties have prompted the use of Drosophila melanogaster (fly) as an instrumental model. Humanized fly models have aided in gaining insight into different cellular disturbances (protein aggregation and misfolding), mitochondrial deficits, and oxidative stress toward causation of Parkinson’s disease. The transgenic and humanized Drosophila model provides a decisive platform to assess the pathogenic properties of rare variants and open a window to analyze the cellular processes and signaling pathways that have been disrupted, which is ultimately manifested by the death of dopaminergic neurons in the brain of Parkinson-affected subjects.

Apart from gaining molecular insight, toxin-induced models of Drosophila recapitulate multiple symptoms of environmental toxin-induced PD. Environmental toxin-induced models of Drosophila have proven to be an efficient means to study gene-environment interactions, which elevate susceptibility for Parkinsonism. Employment of Drosophila to scrutinize gene-environment interactions has led to the screening of many genetic risk factors. Additionally, the rapid development of genome manipulation technologies have paced up the development of more realistic models, which can precisely replicate all pathological features of the disease. This should be worthwhile to elucidate uncharted genetic and environmental risk factors, which are responsible for the complex pathogenesis associated with Parkinson’s disease. The ease of genetic manipulations that mimic symptoms of PD in Drosophila makes it one of the most favorite model organisms for analyzing the underlying cause of PD, the second most prevalent neurological disorder after Alzheimer’s disease.

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References

  • Abeliovich, A., Schmitz, Y., Fariñas, I., Choi-Lundberg, D., Ho, W.-H., Castillo, P. E., Shinsky, N., Verdugo, J. M. G., Armanini, M., & Ryan, A. (2000). Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron, 25(1), 239–252.

    Article  CAS  PubMed  Google Scholar 

  • Abou-Sleiman, P. M., Muqit, M. M., & Wood, N. W. (2006). Expanding insights of mitochondrial dysfunction in Parkinson’s disease. Nature Reviews Neuroscience, 7(3), 207.

    Article  CAS  PubMed  Google Scholar 

  • Adams, R. D., Van Bogaert, L., & Vander Eecken, H. (1964). Striato-nigral degeneration. Journal of Neuropathology & Experimental Neurology, 23(4), 584–608.

    CAS  Google Scholar 

  • Agim, Z. S., & Cannon, J. R. (2015). Dietary factors in the etiology of Parkinson’s disease. BioMed Research International, 2015.

    Google Scholar 

  • Ambegaokar, S. S., Roy, B., & Jackson, G. R. (2010). Neurodegenerative models in Drosophila: Polyglutamine disorders, Parkinson disease, and amyotrophic lateral sclerosis. Neurobiology of Disease, 40(1), 29–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Auluck, P. K., Chan, H. E., Trojanowski, J. Q., Lee, V. M.-Y., & Bonini, N. M. (2002). Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson’s disease. Science, 295(5556), 865–868.

    Article  CAS  PubMed  Google Scholar 

  • Ayajuddin, M., Das, A., Phom, L., Modi, P., Chaurasia, R., Koza, Z., Thepa, A., Jamir, N., Singh, P. R., & Longkumer, S. (2018). Parkinson’s disease: Insights from Drosophila model. In Drosophila melanogaster-model for recent advances in genetics and therapeutics. IntechOpen.

    Google Scholar 

  • Balija, M. B. G., Griesinger, C., Herzig, A., Zweckstetter, M., & Jäckle, H. (2011). Pre-fibrillar α-synuclein mutants cause Parkinson’s disease-like non-motor symptoms in Drosophila. PLoS One, 6(9), e24701.

    Article  CAS  Google Scholar 

  • Bayersdorfer, F., Voigt, A., Schneuwly, S., & Botella, J. A. (2010). Dopamine-dependent neurodegeneration in Drosophila models of familial and sporadic Parkinson’s disease. Neurobiology of Disease, 40(1), 113–119.

    Article  CAS  PubMed  Google Scholar 

  • Betarbet, R., Canet-Aviles, R. M., Sherer, T. B., Mastroberardino, P. G., McLendon, C., Kim, J.-H., Lund, S., Na, H.-M., Taylor, G., & Bence, N. F. (2006). Intersecting pathways to neurodegeneration in Parkinson’s disease: Effects of the pesticide rotenone on DJ-1, α-synuclein, and the ubiquitin–proteasome system. Neurobiology of Disease, 22(2), 404–420.

    Article  CAS  PubMed  Google Scholar 

  • Bingol, B., Tea, J. S., Phu, L., Reichelt, M., Bakalarski, C. E., Song, Q., Foreman, O., Kirkpatrick, D. S., & Sheng, M. (2014). The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature, 510(7505), 370.

    Article  CAS  PubMed  Google Scholar 

  • Bonnet, A. M., & Czernecki, V. (2013). Non-motor symptoms in Parkinson’s disease: Cognition and behavior. Geriatrie et Psychologie Neuropsychiatrie du Vieillissement, 11(3), 295–304.

    PubMed  Google Scholar 

  • Botella, J. A., Bayersdorfer, F., & Schneuwly, S. (2008). Superoxide dismutase overexpression protects dopaminergic neurons in a Drosophila model of Parkinson’s disease. Neurobiology of Disease, 30(1), 65–73.

    Article  CAS  PubMed  Google Scholar 

  • Botella, J. A., Bayersdorfer, F., Gmeiner, F., & Schneuwly, S. (2009). Modelling Parkinson’s disease in Drosophila. Neuromolecular Medicine, 11(4), 268.

    Article  CAS  PubMed  Google Scholar 

  • Bouhouche, A., Tibar, H., Ben El Haj, R., El Bayad, K., Razine, R., Tazrout, S., Skalli, A., Bouslam, N., Elouardi, L., & Benomar, A. (2017). LRRK2 G2019S mutation: Prevalence and clinical features in Moroccans with Parkinson’s disease. Parkinson’s Disease, 2017.

    Google Scholar 

  • Brooks, A., Chadwick, C., Gelbard, H., Cory-Slechta, D., & Federoff, H. (1999). Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Research, 823(1–2), 1–10.

    Article  CAS  PubMed  Google Scholar 

  • Brown, T. P., Rumsby, P. C., Capleton, A. C., Rushton, L., & Levy, L. S. (2005). Pesticides and Parkinson’s disease—is there a link? Environmental Health Perspectives, 114(2), 156–164.

    Article  PubMed Central  Google Scholar 

  • Burré, J. (2015). The synaptic function of α-synuclein. Journal of Parkinson’s Disease, 5(4), 699–713.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bus, J. S., Aust, S. D., & Gibson, J. E. (1976). Paraquat toxicity: Proposed mechanism of action involving lipid peroxidation. Environmental Health Perspectives, 16, 139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Butler, E. K., Voigt, A., Lutz, A. K., Toegel, J. P., Gerhardt, E., Karsten, P., Falkenburger, B., Reinartz, A., Winklhofer, K. F., & Schulz, J. B. (2012). The mitochondrial chaperone protein TRAP1 mitigates α-Synuclein toxicity. PLoS Genetics, 8(2), e1002488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cannon, J. R., & Greenamyre, J. T. (2011). The role of environmental exposures in neurodegeneration and neurodegenerative diseases. Toxicological Sciences, 124(2), 225–250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cassar, M., Issa, A.-R., Riemensperger, T., Petitgas, C., Rival, T., Coulom, H., Iché-Torres, M., Han, K.-A., & Birman, S. (2014). A dopamine receptor contributes to paraquat-induced neurotoxicity in Drosophila. Human Molecular Genetics, 24(1), 197–212.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Castello, P. R., Drechsel, D. A., & Patel, M. (2007). Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain. Journal of Biological Chemistry, 282(19), 14186–14193.

    Article  CAS  Google Scholar 

  • Cesari, R., Martin, E. S., Calin, G. A., Pentimalli, F., Bichi, R., McAdams, H., Trapasso, F., Drusco, A., Shimizu, M., & Masciullo, V. (2003). Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25–q27. Proceedings of the National Academy of Sciences, 100(10), 5956–5961.

    Article  CAS  Google Scholar 

  • Chai, C., & Lim, K.-L. (2013). Genetic insights into sporadic Parkinson’s disease pathogenesis. Current Genomics, 14(8), 486–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chance, B., & Hollunger, G. (1963). Inhibition of electron and energy transfer in mitochondria I. Effects of Amytal, thiopental, rotenone, progesterone, and methylene glycol. Journal of Biological Chemistry, 238(1), 418–431.

    CAS  Google Scholar 

  • Charcot, J. M. (1879). Lectures on the diseases of the nervous system: Delivered at la Salpêtrière. Philadelphia: Lea.

    Book  Google Scholar 

  • Chartier-Harlin, M.-C., Kachergus, J., Roumier, C., Mouroux, V., Douay, X., Lincoln, S., Levecque, C., Larvor, L., Andrieux, J., & Hulihan, M. (2004). α-synuclein locus duplication as a cause of familial Parkinson’s disease. The Lancet, 364(9440), 1167–1169.

    Article  CAS  Google Scholar 

  • Chaudhuri, A., Bowling, K., Funderburk, C., Lawal, H., Inamdar, A., Wang, Z., & O’Donnell, J. M. (2007). Interaction of genetic and environmental factors in a Drosophila parkinsonism model. Journal of Neuroscience, 27(10), 2457–2467.

    Article  CAS  PubMed  Google Scholar 

  • Chen, A., Wilburn, P., Hao, X., & Tully, T. (2014). Walking deficits and centrophobism in an α-synuclein fly model of Parkinson’s disease. Genes, Brain and Behavior, 13(8), 812–820.

    Article  CAS  Google Scholar 

  • Chouliaras, L., Sierksma, A., Kenis, G., Prickaerts, J., Lemmens, M., Brasnjevic, I., van Donkelaar, E., Martinez-Martinez, P., Losen, M., & De Baets, M. (2010). Gene-environment interaction research and transgenic mouse models of Alzheimer’s disease. International Journal of Alzheimer’s Disease, 2010.

    Google Scholar 

  • Cirnaru, M. D., Marte, A., Belluzzi, E., Russo, I., Gabrielli, M., Longo, F., Arcuri, L., Murru, L., Bubacco, L., & Matteoli, M. (2014). LRRK2 kinase activity regulates synaptic vesicle trafficking and neurotransmitter release through modulation of LRRK2 macro-molecular complex. Frontiers in Molecular Neuroscience, 7, 49.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Clark, I. E., Dodson, M. W., Jiang, C., Cao, J. H., Huh, J. R., Seol, J. H., Yoo, S. J., Hay, B. A., & Guo, M. (2006). Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature, 441(7097), 1162.

    Article  CAS  PubMed  Google Scholar 

  • Conradi, S. E., Olanoff, L. S., & Dawson, W. T., Jr. (1983). Fatality due to paraquat intoxication: Confirmation by postmortem tissue analysis. American Journal of Clinical Pathology, 80(5), 771–776.

    Article  CAS  PubMed  Google Scholar 

  • Cooper, A. A., Gitler, A. D., Cashikar, A., Haynes, C. M., Hill, K. J., Bhullar, B., Liu, K., Xu, K., Strathearn, K. E., & Liu, F. (2006). α-Synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson’s models. Science, 313(5785), 324–328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cording, A. C., Shiaelis, N., Petridi, S., Middleton, C. A., Wilson, L. G., & Elliott, C. J. (2017). Targeted kinase inhibition relieves slowness and tremor in a Drosophila model of LRRK2 Parkinson’s disease. npj Parkinson’s Disease, 3(1), 34.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cornelissen, T., Vilain, S., Vints, K., Gounko, N., Verstreken, P., & Vandenberghe, W. (2018). Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila. eLife, 7, e35878.

    Article  PubMed  PubMed Central  Google Scholar 

  • Costello, S., Cockburn, M., Bronstein, J., Zhang, X., & Ritz, B. (2009). Parkinson’s disease and residential exposure to maneb and paraquat from agricultural applications in the central valley of California. American Journal of Epidemiology, 169(8), 919–926.

    Article  PubMed  PubMed Central  Google Scholar 

  • Coulom, H., & Birman, S. (2004). Chronic exposure to rotenone models sporadic Parkinson’s disease in Drosophila melanogaster. Journal of Neuroscience, 24(48), 10993–10998.

    Article  CAS  PubMed  Google Scholar 

  • Damier, P., Hirsch, E., Agid, Y., & Graybiel, A. (1999). The substantia nigra of the human brain: II. Patterns of loss of dopamine-containing neurons in Parkinson’s disease. Brain, 122(8), 1437–1448.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Davis, M. Y., Trinh, K., Thomas, R. E., Yu, S., Germanos, A. A., Whitley, B. N., Sardi, S. P., Montine, T. J., & Pallanck, L. J. (2016). Glucocerebrosidase deficiency in Drosophila results in α-synuclein-independent protein aggregation and neurodegeneration. PLoS Genetics, 12(3), e1005944.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dawson, T. M., Golde, T. E., & Lagier-Tourenne, C. (2018). Animal models of neurodegenerative diseases. Nature Neuroscience, 21(10), 1370–1379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dimant, H., Ebrahimi-Fakhari, D., & McLean, P. J. (2012). Molecular chaperones and co-chaperones in Parkinson disease. The Neuroscientist, 18(6), 589–601.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dinter, E., Saridaki, T., Nippold, M., Plum, S., Diederichs, L., Komnig, D., Fensky, L., May, C., Marcus, K., & Voigt, A. (2016). Rab7 induces clearance of α-synuclein aggregates. Journal of Neurochemistry, 138(5), 758–774.

    Article  CAS  PubMed  Google Scholar 

  • Fato, R., Bergamini, C., Bortolus, M., Maniero, A. L., Leoni, S., Ohnishi, T., & Lenaz, G. (2009). Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1787(5), 384–392.

    Article  CAS  Google Scholar 

  • Feany, M. B., & Bender, W. W. (2000). A Drosophila model of Parkinson’s disease. Nature, 404(6776), 394.

    Article  CAS  PubMed  Google Scholar 

  • Fernagut, P.-O., Hutson, C., Fleming, S., Tetreaut, N., Salcedo, J., Masliah, E., & Chesselet, M. (2007). Behavioral and histopathological consequences of paraquat intoxication in mice: Effects of α-synuclein over-expression. Synapse, 61(12), 991–1001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Filograna, R., Godena, V. K., Sanchez-Martinez, A., Ferrari, E., Casella, L., Beltramini, M., Bubacco, L., Whitworth, A. J., & Bisaglia, M. (2016). SOD-mimetic M40403 is protective in cell and fly models of paraquat toxicity: Implications for Parkinson disease. Journal of Biological Chemistry, M115, 708057.

    Google Scholar 

  • Fuchs, J., Nilsson, C., Kachergus, J., Munz, M., Larsson, E.-M., Schüle, B., Langston, J., Middleton, F., Ross, O., & Hulihan, M. (2007). Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication. Neurology, 68(12), 916–922.

    Article  CAS  PubMed  Google Scholar 

  • Fujiwara, H., Hasegawa, M., Dohmae, N., Kawashima, A., Masliah, E., Goldberg, M. S., Shen, J., Takio, K., & Iwatsubo, T. (2002). α-Synuclein is phosphorylated in synucleinopathy lesions. Nature Cell Biology, 4(2), 160.

    Article  CAS  PubMed  Google Scholar 

  • Gandhi, S., Muqit, M., Stanyer, L., Healy, D., Abou-Sleiman, P., Hargreaves, I., Heales, S., Ganguly, M., Parsons, L., & Lees, A. (2006). PINK1 protein in normal human brain and Parkinson’s disease. Brain, 129(7), 1720–1731.

    Article  CAS  PubMed  Google Scholar 

  • Gandhi, P. N., Chen, S. G., & Wilson-Delfosse, A. L. (2009). Leucine-rich repeat kinase 2 (LRRK2): A key player in the pathogenesis of Parkinson’s disease. Journal of Neuroscience Research, 87(6), 1283–1295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gehrke, S., Imai, Y., Sokol, N., & Lu, B. (2010). Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature, 466(7306), 637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gillet, J.-P., Varma, S., & Gottesman, M. M. (2013). The clinical relevance of cancer cell lines. Journal of the National Cancer Institute, 105(7), 452–458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Godena, V. K., Brookes-Hocking, N., Moller, A., Shaw, G., Oswald, M., Sancho, R. M., Miller, C. C., Whitworth, A. J., & De Vos, K. J. (2014). Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations. Nature Communications, 5, 5245.

    Article  CAS  PubMed  Google Scholar 

  • Gomez-Suaga, P., Luzon-Toro, B., Churamani, D., Zhang, L., Bloor-Young, D., Patel, S., Woodman, P. G., Churchill, G. C., & Hilfiker, S. (2011). Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP. Human Molecular Genetics, 21(3), 511–525.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Greenfield, J., & Bosanquet, F. D. (1953). The brain-stem lesions in Parkinsonism. Journal of Neurology, Neurosurgery, and Psychiatry, 16(4), 213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hales, K. G., Korey, C. A., Larracuente, A. M., & Roberts, D. M. (2015). Genetics on the fly: A primer on the Drosophila model system. Genetics, 201(3), 815–842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hardy, J., Cai, H., Cookson, M. R., Gwinn-Hardy, K., & Singleton, A. (2006). Genetics of Parkinson’s disease and parkinsonism. Annals of Neurology, 60(4), 389–398.

    Article  CAS  PubMed  Google Scholar 

  • Haywood, A. F., & Staveley, B. E. (2006). Mutant α-synuclein-induced degeneration is reduced by parkin in a fly model of Parkinson’s disease. Genome, 49(5), 505–510.

    Article  CAS  PubMed  Google Scholar 

  • Hindle, S., Afsari, F., Stark, M., Middleton, C. A., Evans, G. J., Sweeney, S. T., & Elliott, C. J. (2013). Dopaminergic expression of the Parkinsonian gene LRRK2-G2019S leads to non-autonomous visual neurodegeneration, accelerated by increased neural demands for energy. Human Molecular Genetics, 22(11), 2129–2140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirth, F. (2010). Drosophila melanogaster in the study of human neurodegeneration. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders), 9(4), 504–523.

    CAS  Google Scholar 

  • Hoehn, M. M., & Yahr, M. D. (1998). Parkinsonism: Onset, progression, and mortality. Neurology, 50(2), 318–318.

    Article  PubMed  Google Scholar 

  • Hosamani, R. (2009). Neuroprotective efficacy of Bacopa monnieri against rotenone induced oxidative stress and neurotoxicity in Drosophila melanogaster. Neurotoxicology, 30(6), 977–985.

    Article  CAS  PubMed  Google Scholar 

  • Hruska, K. S., Goker-Alpan, O., & Sidransky, E. (2006). Gaucher disease and the synucleinopathies. BioMed Research International, 2006.

    Google Scholar 

  • Imai, Y., Gehrke, S., Wang, H. Q., Takahashi, R., Hasegawa, K., Oota, E., & Lu, B. (2008). Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila. The EMBO Journal, 27(18), 2432–2443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inamdar, A. A., Chaudhuri, A., & O’Donnell, J. (2012). The protective effect of minocycline in a paraquat-induced Parkinson’s disease model in Drosophila is modified in altered genetic backgrounds. Parkinson’s Disease, 2012.

    Google Scholar 

  • Islam, M. S., & Moore, D. J. (2017). Mechanisms of LRRK2-dependent neurodegeneration: Role of enzymatic activity and protein aggregation. Biochemical Society Transactions, 45(1), 163–172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jagmag, S. A., Tripathi, N., Shukla, S. D., Maiti, S., & Khurana, S. (2016). Evaluation of models of Parkinson’s disease. Frontiers in Neuroscience, 9, 503.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kamel, F., Tanner, C., Umbach, D., Hoppin, J., Alavanja, M., Blair, A., Comyns, K., Goldman, S., Korell, M., & Langston, J. (2006). Pesticide exposure and self-reported Parkinson’s disease in the agricultural health study. American Journal of Epidemiology, 165(4), 364–374.

    Article  PubMed  Google Scholar 

  • Kawajiri, S., Saiki, S., Sato, S., & Hattori, N. (2011). Genetic mutations and functions of PINK1. Trends in Pharmacological Sciences, 32(10), 573–580.

    Article  CAS  PubMed  Google Scholar 

  • Kim, Y., Park, J., Kim, S., Song, S., Kwon, S.-K., Lee, S.-H., Kitada, T., Kim, J.-M., & Chung, J. (2008). PINK1 controls mitochondrial localization of Parkin through direct phosphorylation. Biochemical and Biophysical Research Communications, 377(3), 975–980.

    Article  CAS  PubMed  Google Scholar 

  • Kinghorn, K. J., Grönke, S., Castillo-Quan, J. I., Woodling, N. S., Li, L., Sirka, E., Gegg, M., Mills, K., Hardy, J., & Bjedov, I. (2016). A Drosophila model of neuronopathic Gaucher disease demonstrates lysosomal-autophagic defects and altered mTOR signalling and is functionally rescued by rapamycin. Journal of Neuroscience, 36(46), 11654–11670.

    Article  CAS  PubMed  Google Scholar 

  • Krüger, R., Kuhn, W., Müller, T., Woitalla, D., Graeber, M., Kösel, S., Przuntek, H., Epplen, J. T., Schols, L., & Riess, O. (1998). AlaSOPro mutation in the gene encoding α-synuclein in Parkinson’s disease. Nature Genetics, 18(2), 106–108.

    Article  PubMed  Google Scholar 

  • Kuzuhara, S., Mori, H., Izumiyama, N., Yoshimura, M., & Ihara, Y. (1988). Lewy bodies are ubiquitinated. Acta Neuropathologica, 75(4), 345–353.

    Article  CAS  PubMed  Google Scholar 

  • Labbé, C., & Ross, O. A. (2014). Association studies of sporadic Parkinson’s disease in the genomic era. Current Genomics, 15(1), 2–10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lakkappa, N., Krishnamurthy, P. T., Yamjala, K., Hwang, S. H., Hammock, B. D., & Babu, B. (2018). Evaluation of antiparkinson activity of PTUPB by measuring dopamine and its metabolites in Drosophila melanogaster: LC–MS/MS method development. Journal of Pharmaceutical and Biomedical Analysis, 149, 457–464.

    Article  CAS  PubMed  Google Scholar 

  • Lascano, R., Muñoz, N., Robert, G., Rodriguez, M., Melchiorre, M., Trippi, V., & Quero, G. (2012). Paraquat: An oxidative stress inducer. In Herbicides-properties, synthesis and control of weeds. InTech.

    Google Scholar 

  • Lawal, H. O., Chang, H.-Y., Terrell, A. N., Brooks, E. S., Pulido, D., Simon, A. F., & Krantz, D. E. (2010). The Drosophila vesicular monoamine transporter reduces pesticide-induced loss of dopaminergic neurons. Neurobiology of Disease, 40(1), 102–112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, S. B., Kim, W., Lee, S., & Chung, J. (2007). Loss of LRRK2/PARK8 induces degeneration of dopaminergic neurons in Drosophila. Biochemical and Biophysical Research Communications, 358(2), 534–539.

    Article  CAS  PubMed  Google Scholar 

  • Lewy, F. H. (1912). Paralysis agitans. I. Pathologische anatomie. In M. Lewandowsky (Ed.), Handbuch der neurologie. Berlin: Springer.

    Google Scholar 

  • Li, T., Yang, D., Sushchky, S., Liu, Z., & Smith, W. W. (2011). Models for LRRK2-linked parkinsonism. Parkinson’s Disease, 2011, 942412.

    PubMed  PubMed Central  Google Scholar 

  • Liao, J., Morin, L. W., & Ahmad, S. T. (2014). Methods to characterize spontaneous and startle-induced locomotion in a rotenone-induced Parkinson’s disease model of Drosophila. JoVE (Journal of Visualized Experiments), 90, e51625.

    Google Scholar 

  • Lin, C.-H., Tsai, P.-I., Wu, R.-M., & Chien, C.-T. (2010). LRRK2 G2019S mutation induces dendrite degeneration through mislocalization and phosphorylation of tau by recruiting autoactivated GSK3β. Journal of Neuroscience, 30(39), 13138–13149.

    Article  CAS  PubMed  Google Scholar 

  • Lin, C.-H., Li, H., Lee, Y.-N., Cheng, Y.-J., Wu, R.-M., & Chien, C.-T. (2015). Lrrk regulates the dynamic profile of dendritic Golgi outposts through the golgin Lava lamp. Journal of Cell Biology, 201411033.

    Google Scholar 

  • Liou, H., Tsai, M., Chen, C., Jeng, J., Chang, Y., Chen, S., & Chen, R. (1997). Environmental risk factors and Parkinson’s disease A case-control study in Taiwan. Neurology, 48(6), 1583–1588.

    Article  CAS  PubMed  Google Scholar 

  • Liu, Z., Wang, X., Yu, Y., Li, X., Wang, T., Jiang, H., Ren, Q., Jiao, Y., Sawa, A., & Moran, T. (2008). A Drosophila model for LRRK2-linked parkinsonism. Proceedings of the National Academy of Sciences, 105(7), 2693–2698.

    Article  CAS  Google Scholar 

  • Liu, L.-F., Song, J.-X., Lu, J.-H., Huang, Y.-Y., Zeng, Y., Chen, L.-L., Durairajan, S. S. K., Han, Q.-B., & Li, M. (2015). Tianma Gouteng Yin, a Traditional Chinese Medicine decoction, exerts neuroprotective effects in animal and cellular models of Parkinson’s disease. Scientific Reports, 5, 16862.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu, B., & Vogel, H. (2009). Drosophila models of neurodegenerative diseases. Annual Review of Pathological Mechanical Disease, 4, 315–342.

    Article  CAS  Google Scholar 

  • MacLeod, D. A., Rhinn, H., Kuwahara, T., Zolin, A., Di Paolo, G., McCabe, B. D., Marder, K. S., Honig, L. S., Clark, L. N., & Small, S. A. (2013). RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson’s disease risk. Neuron, 77(3), 425–439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manning-Bog, A. B., McCormack, A. L., Li, J., Uversky, V. N., Fink, A. L., & Di Monte, D. A. (2002). The herbicide paraquat causes up-regulation and aggregation of α-synuclein in mice paraquat and α-synuclein. Journal of Biological Chemistry, 277(3), 1641–1644.

    Article  CAS  Google Scholar 

  • Maor, G., Rencus-Lazar, S., Filocamo, M., Steller, H., Segal, D., & Horowitz, M. (2013). Unfolded protein response in Gaucher disease: From human to Drosophila. Orphanet Journal of Rare Diseases, 8(1), 140.

    Article  PubMed  PubMed Central  Google Scholar 

  • Maor, G., Cabasso, O., Krivoruk, O., Rodriguez, J., Steller, H., Segal, D., & Horowitz, M. (2016). The contribution of mutant GBA to the development of Parkinson disease in Drosophila. Human Molecular Genetics, 25(13), 2712–2727.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marín, I. (2006). The Parkinson disease gene LRRK2: Evolutionary and structural insights. Molecular Biology and Evolution, 23(12), 2423–2433.

    Article  PubMed  CAS  Google Scholar 

  • Maroteaux, L., Campanelli, J. T., & Scheller, R. H. (1988). Synuclein: A neuron-specific protein localized to the nucleus and presynaptic nerve terminal. The Journal of Neuroscience, 8, 2804–2815.

    Google Scholar 

  • Marshall, L. E., & Himes, R. H. (1978). Rotenone inhibition of tubulin self-assembly. Biochimica et Biophysica Acta (BBA)-General Subjects, 543(4), 590–594.

    Article  CAS  Google Scholar 

  • Martin, C. A., Barajas, A., Lawless, G., Lawal, H. O., Assani, K., Lumintang, Y. P., Nunez, V., & Krantz, D. E. (2014a). Synergistic effects on dopamine cell death in a Drosophila model of chronic toxin exposure. Neurotoxicology, 44, 344–351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin, I., Kim, J. W., Lee, B. D., Kang, H. C., Xu, J.-C., Jia, H., Stankowski, J., Kim, M.-S., Zhong, J., & Kumar, M. (2014b). Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson’s disease. Cell, 157(2), 472–485.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martinez, A., Lectez, B., Ramirez, J., Popp, O., Sutherland, J. D., Urbé, S., Dittmar, G., Clague, M. J., & Mayor, U. (2017). Quantitative proteomic analysis of Parkin substrates in Drosophila neurons. Molecular Neurodegeneration, 12(1), 29.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mata, I. F., Wilhoite, G. J., Yearout, D., Bacon, J. A., Cornejo-Olivas, M., Mazzetti, P., Marca, V., Ortega, O., Acosta, O., & Cosentino, C. (2011). Lrrk2 p. Q1111H substitution and Parkinson’s disease in Latin America. Parkinsonism & Related Disorders, 17(8), 629–631.

    Article  Google Scholar 

  • Mazzulli, J. R., Zunke, F., Tsunemi, T., Toker, N. J., Jeon, S., Burbulla, L. F., Patnaik, S., Sidransky, E., Marugan, J. J., & Sue, C. M. (2016). Activation of β-glucocerebrosidase reduces pathological α-synuclein and restores lysosomal function in Parkinson’s patient midbrain neurons. Journal of Neuroscience, 36(29), 7693–7706.

    Article  CAS  PubMed  Google Scholar 

  • McCormack, A. L., Thiruchelvam, M., Manning-Bog, A. B., Thiffault, C., Langston, J. W., Cory-Slechta, D. A., & Di Monte, D. A. (2002). Environmental risk factors and Parkinson’s disease: Selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiology of Disease, 10(2), 119–127.

    Article  CAS  PubMed  Google Scholar 

  • Miller, D., Hague, S., Clarimon, J., Baptista, M., Gwinn-Hardy, K., Cookson, M., & Singleton, A. (2004). α-synuclein in blood and brain from familial Parkinson disease with SNCA locus triplication. Neurology, 62(10), 1835–1838.

    Article  CAS  PubMed  Google Scholar 

  • Muñoz-Soriano, V., & Paricio, N. (2011). Drosophila models of Parkinson’s disease: Discovering relevant pathways and novel therapeutic strategies. Parkinson’s Disease, 2011.

    Google Scholar 

  • Nagoshi, E. (2018). Drosophila models of sporadic Parkinson’s disease. International Journal of Molecular Sciences, 19(11), 3343.

    Article  PubMed Central  CAS  Google Scholar 

  • Neumann, J., Bras, J., Deas, E., O’sullivan, S. S., Parkkinen, L., Lachmann, R. H., Li, A., Holton, J., Guerreiro, R., & Paudel, R. (2009). Glucocerebrosidase mutations in clinical and pathologically proven Parkinson’s disease. Brain, 132(7), 1783–1794.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ordonez, D. G., Lee, M. K., & Feany, M. B. (2018). α-synuclein induces mitochondrial dysfunction through spectrin and the actin cytoskeleton. Neuron, 97(1), 108–124. e106.

    Article  CAS  PubMed  Google Scholar 

  • Park, J., Lee, S. B., Lee, S., Kim, Y., Song, S., Kim, S., Bae, E., Kim, J., Shong, M., & Kim, J.-M. (2006). Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature, 441(7097), 1157.

    Article  CAS  PubMed  Google Scholar 

  • Parkinson, J. (1817). An essay on the shaking palsy Whittingham and Rowland for Sherwood. London: Needly and Jones.

    Google Scholar 

  • Penney, J., Tsurudome, K., Liao, E. H., Kauwe, G., Gray, L., Yanagiya, A., Calderon, M. R., Sonenberg, N., & Haghighi, A. P. (2016). LRRK2 regulates retrograde synaptic compensation at the Drosophila neuromuscular junction. Nature Communications, 7, 12188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pesah, Y., Pham, T., Burgess, H., Middlebrooks, B., Verstreken, P., Zhou, Y., Harding, M., Bellen, H., & Mardon, G. (2004). Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress. Development, 131(9), 2183–2194.

    Article  CAS  PubMed  Google Scholar 

  • Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., & Boyer, R. (1997). Mutation in the α-synuclein gene identified in families with Parkinson’s disease. Science, 276(5321), 2045–2047.

    Article  CAS  PubMed  Google Scholar 

  • Poole, A. C., Thomas, R. E., Andrews, L. A., McBride, H. M., Whitworth, A. J., & Pallanck, L. J. (2008). The PINK1/Parkin pathway regulates mitochondrial morphology. Proceedings of the National Academy of Sciences, 105(5), 1638–1643.

    Article  CAS  Google Scholar 

  • Raina, S., Kumar, V., Kaushal, S., & Gupta, D. (2008). Two cases of Paraquat poisoning from Himachal Pradesh. Journal, Indian Academy of Clinical Medicine, 9, 130–132.

    Google Scholar 

  • Rauch, J., Volinsky, N., Romano, D., & Kolch, W. (2011). The secret life of kinases: Functions beyond catalysis. Cell Communication and Signaling, 9(1), 23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanchez-Martinez, A., Beavan, M., Gegg, M. E., Chau, K.-Y., Whitworth, A. J., & Schapira, A. H. (2016). Parkinson disease-linked GBA mutation effects reversed by molecular chaperones in human cell and fly models. Scientific Reports, 6, 31380.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sang, T.-K., Chang, H.-Y., Lawless, G. M., Ratnaparkhi, A., Mee, L., Ackerson, L. C., Maidment, N. T., Krantz, D. E., & Jackson, G. R. (2007). A Drosophila model of mutant human parkin-induced toxicity demonstrates selective loss of dopaminergic neurons and dependence on cellular dopamine. Journal of Neuroscience, 27(5), 981–992.

    Article  CAS  PubMed  Google Scholar 

  • Sanz, F. J., Solana-Manrique, C., Muñoz-Soriano, V., Calap-Quintana, P., Moltó, M. D., & Paricio, N. (2017). Identification of potential therapeutic compounds for Parkinson’s disease using Drosophila and human cell models. Free Radical Biology and Medicine, 108, 683–691.

    Article  CAS  PubMed  Google Scholar 

  • Schulz, J. B. (2007). Mechanisms of neurodegeneration in idiopathic Parkinson’s disease. Parkinsonism & Related Disorders, 13, S306–S308.

    Article  Google Scholar 

  • Sherer, T. B., Betarbet, R., Testa, C. M., Seo, B. B., Richardson, J. R., Kim, J. H., Miller, G. W., Yagi, T., Matsuno-Yagi, A., & Greenamyre, J. T. (2003). Mechanism of toxicity in rotenone models of Parkinson’s disease. Journal of Neuroscience, 23(34), 10756–10764.

    Article  CAS  PubMed  Google Scholar 

  • Shimura, H., Hattori, N., Kubo, S. I., Yoshikawa, M., Kitada, T., Matsumine, H., Asakawa, S., Minoshima, S., Yamamura, Y., & Shimizu, N. (1999). Immunohistochemical and subcellular localization of Parkin protein: Absence of protein in autosomal recessive juvenile parkinsonism patients. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 45(5), 668–672.

    Article  CAS  Google Scholar 

  • Shimura, H., Hattori, N., Kubo, S.-i., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., & Tanaka, K. (2000). Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nature Genetics, 25(3), 302.

    Article  CAS  PubMed  Google Scholar 

  • Shukla, A. K., Pragya, P., Chaouhan, H. S., Tiwari, A. K., Patel, D. K., Abdin, M. Z., & Chowdhuri, D. K. (2014). Heat shock protein-70 (Hsp-70) suppresses paraquat-induced neurodegeneration by inhibiting JNK and caspase-3 activation in Drosophila model of Parkinson’s disease. PLoS One, 9(6), e98886.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shukla, A. K., Ratnasekhar, C., Pragya, P., Chaouhan, H. S., Patel, D. K., Chowdhuri, D. K., & Mudiam, M. K. R. (2016). Metabolomic analysis provides insights on paraquat-induced Parkinson-like symptoms in drosophila melanogaster. Molecular Neurobiology, 53(1), 254–269.

    Article  CAS  PubMed  Google Scholar 

  • Singleton, A., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., & Nussbaum, R. (2003). α-Synuclein locus triplication causes Parkinson’s disease. Science, 302(5646), 841–841.

    Article  CAS  PubMed  Google Scholar 

  • Spillantini, M. G., Crowther, R. A., Jakes, R., Hasegawa, M., & Goedert, M. (1998). α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proceedings of the National Academy of Sciences, 95(11), 6469–6473.

    Article  CAS  Google Scholar 

  • St Laurent, G., Tackett, M. R., Nechkin, S., Shtokalo, D., Antonets, D., Savva, Y. A., Maloney, R., Kapranov, P., Lawrence, C. E., & Reenan, R. A. (2013). Genome-wide analysis of A-to-I RNA editing by single-molecule sequencing in Drosophila. Nature Structural & Molecular Biology, 20(11), 1333.

    Article  CAS  Google Scholar 

  • Stephano, F., Nolte, S., Hoffmann, J., El-Kholy, S., Frieling, J., Bruchhaus, I., Fink, C., & Roeder, T. (2018). Impaired Wnt signaling in dopamine containing neurons is associated with pathogenesis in a rotenone triggered Drosophila Parkinson’s disease model. Scientific Reports, 8(1), 2372.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sudati, J. H., Vieira, F. A., Pavin, S. S., Dias, G. R. M., Seeger, R. L., Golombieski, R., Athayde, M. L., Soares, F. A., Rocha, J. B. T., & Barbosa, N. V. (2013). Valeriana officinalis attenuates the rotenone-induced toxicity in Drosophila melanogaster. Neurotoxicology, 37, 118–126.

    Article  CAS  PubMed  Google Scholar 

  • Suzuki, M., Fujikake, N., Takeuchi, T., Kohyama-Koganeya, A., Nakajima, K., Hirabayashi, Y., Wada, K., & Nagai, Y. (2015). Glucocerebrosidase deficiency accelerates the accumulation of proteinase K-resistant α-synuclein and aggravates neurodegeneration in a Drosophila model of Parkinson’s disease. Human Molecular Genetics, 24(23), 6675–6686.

    Article  CAS  PubMed  Google Scholar 

  • Tain, L. S., Mortiboys, H., Tao, R. N., Ziviani, E., Bandmann, O., & Whitworth, A. J. (2009). Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss. Nature Neuroscience, 12(9), 1129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Talpade, D. J., Greene, J. G., Higgins, D. S., Jr., & Greenamyre, J. T. (2000). In vivo labeling of mitochondrial complex I (NADH: Ubiquinone oxidoreductase) in rat brain using [3H] dihydrorotenone. Journal of Neurochemistry, 75(6), 2611–2621.

    Article  CAS  PubMed  Google Scholar 

  • Tayebi, N., Walker, J., Stubblefield, B., Orvisky, E., LaMarca, M., Wong, K., Rosenbaum, H., Schiffmann, R., Bembi, B., & Sidransky, E. (2003). Gaucher disease with parkinsonian manifestations: Does glucocerebrosidase deficiency contribute to a vulnerability to parkinsonism? Molecular Genetics and Metabolism, 79(2), 104–109.

    Article  CAS  PubMed  Google Scholar 

  • Thomas, B., & Beal, M. F. (2011). Molecular insights into Parkinson’s disease. F1000 Medicine Reports, 3, 7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Todorova, A., Jenner, P., & Chaudhuri, K. R. (2014). Non-motor Parkinson’s: Integral to motor Parkinson’s, yet often neglected. Practical Neurology, 14(5), 310–322.

    Article  PubMed  PubMed Central  Google Scholar 

  • Trétiakoff, C. (1919). Contribution a l’etude de l’Anatomie pathologique du Locus Niger de Soemmering avec quelques deduction relatives a la pathogenie des troubles du tonus musculaire et de la maladie de Parkinson. Theses de Paris.

    Google Scholar 

  • Trinh, K., Moore, K., Wes, P. D., Muchowski, P. J., Dey, J., Andrews, L., & Pallanck, L. J. (2008). Induction of the phase II detoxification pathway suppresses neuron loss in Drosophila models of Parkinson’s disease. Journal of Neuroscience, 28(2), 465–472.

    Article  CAS  PubMed  Google Scholar 

  • Trotta, L., Guella, I., Soldà, G., Sironi, F., Tesei, S., Canesi, M., Pezzoli, G., Goldwurm, S., Duga, S., & Asselta, R. (2012). SNCA and MAPT genes: Independent and joint effects in Parkinson disease in the Italian population. Parkinsonism & Related Disorders, 18(3), 257–262.

    Article  Google Scholar 

  • Vives-Bauza, C., Zhou, C., Huang, Y., Cui, M., de Vries, R. L., Kim, J., May, J., Tocilescu, M. A., Liu, W., & Ko, H. S. (2010). PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proceedings of the National Academy of Sciences, 107(1), 378–383.

    Article  CAS  Google Scholar 

  • Wakabayashi, K., Engelender, S., Yoshimoto, M., Tsuji, S., Ross, C. A., & Takahashi, H. (2000). Synphilin-1 is present in Lewy bodies in Parkinson’s disease. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 47(4), 521–523.

    Article  CAS  Google Scholar 

  • Wallings, R., Manzoni, C., & Bandopadhyay, R. (2015). Cellular processes associated with LRRK2 function and dysfunction. The FEBS Journal, 282(15), 2806–2826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, D., Tang, B., Zhao, G., Pan, Q., Xia, K., Bodmer, R., & Zhang, Z. (2008). Dispensable role of Drosophila ortholog of LRRK2 kinase activity in survival of dopaminergic neurons. Molecular Neurodegeneration, 3(1), 3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whitworth, A. J., Wes, P. D., & Pallanck, L. J. (2006). Drosophila models pioneer a new approach to drug discovery for Parkinson’s disease. Drug Discovery Today, 11(3–4), 119–126.

    Article  CAS  PubMed  Google Scholar 

  • Wu, B., Song, B., Tian, S., Huo, S., Cui, C., Guo, Y., & Liu, H. (2012). Central nervous system damage due to acute paraquat poisoning: A neuroimaging study with 3.0 T MRI. Neurotoxicology, 33(5), 1330–1337.

    Article  CAS  PubMed  Google Scholar 

  • Xiong, Y., & Yu, J. (2018). Modeling Parkinson’s disease in Drosophila: What have we learned for dominant traits? Frontiers in Neurology, 9, 228.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang, Y., Ouyang, Y., Yang, L., Beal, M. F., McQuibban, A., Vogel, H., & Lu, B. (2008). Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proceedings of the National Academy of Sciences, 105(19), 7070–7075.

    Article  CAS  Google Scholar 

  • Yin, G., Da Fonseca, T. L., Eisbach, S. E., Anduaga, A. M., Breda, C., Orcellet, M. L., Szegő, É. M., Guerreiro, P., Lázaro, D. F., & Braus, G. H. (2014). α-Synuclein interacts with the switch region of Rab 8a in a Ser129 phosphorylation-dependent manner. Neurobiology of Disease, 70, 149–161.

    Article  CAS  PubMed  Google Scholar 

  • Yue, Z. (2009). LRRK2 in Parkinson’s disease: In vivo models and approaches for understanding pathogenic roles. The FEBS Journal, 276(22), 6445–6454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zanon, A., Kalvakuri, S., Rakovic, A., Foco, L., Guida, M., Schwienbacher, C., Serafin, A., Rudolph, F., Trilck, M., & Grünewald, A. (2017). SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and Drosophila. Human Molecular Genetics, 26(13), 2412–2425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zarranz, J. J., Alegre, J., Gómez-Esteban, J. C., Lezcano, E., Ros, R., Ampuero, I., Vidal, L., Hoenicka, J., Rodriguez, O., & Atarés, B. (2004). The new mutation, E46K, of α-synuclein causes parkinson and Lewy body dementia. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 55(2), 164–173.

    Article  CAS  Google Scholar 

  • Zuberi, A., & Lutz, C. (2017). Mouse models for drug discovery. Can new tools and technology improve translational power? ILAR Journal, 57(2), 178–185.

    Article  CAS  Google Scholar 

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    Souradip Chatterjee, Ashim Mukherjee & Mousumi Mutsuddi

  2. Department of Biology, Johns Hopkins University, Baltimore, MD, USA

    Pradeep Kumar Bhaskar

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    Mousumi Mutsuddi

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Chatterjee, S., Bhaskar, P.K., Mukherjee, A., Mutsuddi, M. (2019). Modeling of Human Parkinson’s Disease in Fly. In: Mutsuddi, M., Mukherjee, A. (eds) Insights into Human Neurodegeneration: Lessons Learnt from Drosophila. Springer, Singapore. https://doi.org/10.1007/978-981-13-2218-1_10

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