ISSN 0564-3783  
Main page
Contacts
Preview papers  
Contents  
Themes
Subscription
Information to authors
Editorial board
Standard version



In Ukrainian

Export citations   UNIMARC   BibTeX   RIS


Drosophila melanogaster model system for the study of human neuropathy and testing of neuroprotectors

Matiytsiv N.P., Chernyk Ya.I.

Review 




SUMMARY. At present, molecular characteristics of the occurrence and development of neurodegenerative diseases some of the most severe and currently incurable ones are yet to be studied in full detail. Therefore, it is still relevant to search for medicines to eliminate, relieve or delay the symptoms of these pathologies. Given the complexity of research in humans, the detection of genes that are associated with the development of neurodegenerative changes, the study of their functioning in various tissues (neuronal and glial) and at different stages of ontogenesis are carried out on model objects. Drosophila melanogaster is one of the best and affordable models to find out the molecular genetic mechanisms of neurodegeneration development, as well as for initial testing of new compounds with neuroprotective properties. Here we discuss the methods of genetic analysis on the Drosophila, the use of D. melanogaster to model neurodegenerative human disorders, the opportunities to use these models as test systems for the study of potential neuroprotectors.

Key words: Drosophila, neurodegeneration, neuroprotectors, brain, UAS / Gal4 system

Tsitologiya i Genetika 2020, vol. 54, no. 3, pp. 81-95

  • Ivan Franko National University of Lviv, Department of Genetics and Biotechnology

E-mail: matiytsiv yahoo.com

Matiytsiv N.P., Chernyk Ya.I. Drosophila melanogaster model system for the study of human neuropathy and testing of neuroprotectors, Tsitol Genet., 2020, vol. 54, no. 3, pp. 81-95.

In "Cytology and Genetics":
N. P. Matiytsiv & Ya. I. Chernyk Drosophila melanogaster as a Model System for the Study of Human Neuropathy and the Testing of Neuroprotectors, Cytol Genet., 2020, vol. 54, no. 3, pp. 243256
DOI: 10.3103/S0095452720030081


References

1. Cuny, G.D., Neurodegenerative diseases: challenges and opportunities, Future Med. Chem, 2012, vol. 4, pp. 16471649.

2. Saxena, S., Funk, M., and Chisholm, D., World Health Assembly adopts comprehensive mental health action plan 20132020, Lancet, 2013, vol. 381, pp. 19701971.

3. Lage, O.M., Ramos, M.C., Calisto, R., Almeida, E., Vasconcelos, V., and Vicente, F., Current screening methodologies in drug discovery for selected human diseases, Mar. Drugs, 2018, vol. 16, no. 8, pp. 279. https://doi.org/10.3390/md16080279

4. Kenney, D., and Borisy, G., Thomas Hunt Morgan at the Marine Biological Laboratory: naturalist and experimentalist, Genetics, 2009, vol. 181, no. 3, pp. 841846.

5. Adams, M., Celniker, S., Holt, R., Evans, C., Gocayne, J., Amanatides, P., Scherer, S., Li, P., Hoskins, R., Galle, R., et al., The genome sequence of Drosophila melanogaster,Science, 2000, vol. 287, no. 5461, pp. 21852195.

6. Pandey, U. and Nichols, C.D., Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery, Pharmacol. Rev., 2011, vol. 63, no. 2, pp. 411436.

7. Millburn, G., Crosby, M., Gramates, L., and Tweedie, S., FlyBase portals to human disease research using Drosophila models, Dis. Models Mech., 2016, vol. 9, no. 3, pp. 245252.

8. Takano-Shimizu-Kouno, T., and Ohsako, T., Humanized flies and resources for cross-species study, Adv. Exp. Med. Biol., 2018, vol. 1076, pp. 277288, https://doi.org/10.1007/978-981-13-0529-0_15

9. Benzer, S., From the gene to behavior, JAMA, 1971, vol. 15, no. 7, pp. 10151022.

10. Mohylyak, I. and Chernyk, Ya., Functioning of glia and neurodegeneration in Drosophila melanogaster, Cytol. Genet., 2017, vol. 51, pp. 202213.

11. Andretic, R., Kim, Y., Jones, F., Han, K., and Greenspan, R., Drosophila D1 dopamine receptor mediates caffeine-induced arousal, Proc. Natl. Acad. Sci. U. S. A., 2008, vol. 105, no. 51, pp. 2039220397. https://doi.org/10.1073/pnas.0806776105

12. Wolf, M. and Rockman, H., Drosophila melanogaster as a model system for genetics of postnatal cardiac function, Drug Discov. Today Dis. Models, 2008, vol. 5, no. 3, pp. 117123.

13. Bilder, D., and Irvine, K., Taking stock of the Drosophila research ecosystem, Genetics, 2017, vol. 206, no. 3, pp. 12271236.

14. Stocker, H. and Gallant, P., Getting started: an overview on raising and handling Drosophila,Methods Mol. Biol., 2008, vol. 420, pp. 2744.

15. St Johnston, D., The art and design of genetic screens: Drosophila melanogaster,Nat. Rev. Genet., 2002, vol. 3, no. 3, pp. 17688.

16. Bokel, C., EMS screens: From mutagenesis to screening and mapping, Methods Mol. Biol., 2008, vol. 420, pp. 119138.

17. Moulton, M. and Letsou, A., Modeling congenital disease and inborn errors of development in Drosophila melanogaster,Dis. Models Mech., 2016, vol. 9, no. 3, pp. 253269.

18. Hales, K., Korey, C., Larracuente, A., and Roberts, D., Genetics on the fly: a primer on the Drosophila model system, Genetics, 2015, vol. 201, no. 3, pp. 815842.

19. Greenspan, R.J., Fly Publishing. The Theory and Practice of Drosophila Genetics, New York: Cold Spring Harbor Lab. Press, 2000.

20. Hummel, T. and Klambt, C., P-element mutagenesis, Methods Mol. Biol., 2008, vol. 420, pp. 97117.

21. Cooley, L., Berg, C., and Spradling, A., Controlling P element insertional mutagenesis, Trends Genet., 1988, vol. 4, no. 9, pp. 254258.

22. OHare, K. and Rubin, G.M., Structures of P transposable elements and their sites of insertion and excision in the Drosophila melanogaster genome, Cell, 1983, vol. 34, no. 1, pp. 2535.

23. Rubin, G.M. and Spradling, A.C., Genetic transformation of Drosophila with transposable element vectors, Science, 1982, vol. 218, no. 4570, pp. 348353.

24. Venken, K.J. and Bellen, H.J., Transgenesis upgrades for Drosophila melanogaster, Development, 2007, vol. 134, no. 20, pp. 35713584.

25. Karess, R.E. and Rubin, G.M., Analysis of P transposable element functions in Drosophila,Cell, 1984, vol. 38, no. 1, pp. 135146.

26. Brand, A.H. and Perrimon, N., Targeted gene expression as a means of altering cell fates and generating dominant phenotypes, Development, 1993, vol. 118, no. 2, pp. 401415.

27. Limmer, S., Weiler, A., Volkenkoff, A., Babatz, F., and Klambt C., The Drosophila blood-brain barrier: development and function of a glial endothelium, Front. Neurosci., 2014, vol. 8. https://doi.org/10.3389/fnins.2014.00365

28. Buchanan, R.L. and Benzer, S., Defective glia in the Drosophila brain degeneration mutant drop-dead, Neuron, 1993, vol. 10, no. 5, pp. 839850.

29. Kretzschmar, D., Hasan, G., Sharma, S., Heisenberg, M., and Benzer, S., The swiss cheese mutant cause glial hyperwrapping and brain degeneration in Drosophila,J. Neurosci., 1997, vol. 17, pp. 74257432.

30. Lush, M., Li, Y., Read, D., Willis, A., and Glynn, P., Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man, Biochem. J., 1998, vol. 332, pp. 14.

31. Rainier, S., Bui, M., Mark, E., Thomas D., Tokarz D., Ming L., Delaney, C, Richardson, R., Albers, J., Matsunami, N., Stevens, J., Coon, H., Leppert, M., and Fink, J., Neuropathy target esterase gene mutations cause motorneuron disease, Am. J. Hum Genet., 2008, vol. 82, pp. 780785.

32. Synofzik, M., Gonzalez, M., Lourenco, C., Coutelier, M., Haack, T., Rebelo, A., Hannequin, D., Strom, T., Prokisch, H., Kernstock, C., Durr, A., Schöls, L., Lima-Martínez., M., Farooq, A., Schiile, R., Stevanin, G., Marques, W., and Ziichner, S., PNPLA6 mutations cause Boucher-Neuha-user and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum, Brain, 2014, vol. 137, pp. 6977.

33. Finley K.D., Edeen P.T., Cumming R.C., Mardahl-Dumesnil M.D., Taylor B.J., Rodriguez, M., Hwang, C., Benedetti, M., and McKeown, M., blue cheese mutations define a novel, conserved gene involved in progressive neural degeneration, J. Neurosci., 2003, vol. 23, no. 4, pp. 12541264.

34. Lim, A. and Kraut R., The Drosophila BEACH family protein, blue cheese, links lysosomal axon transport with motor neuron degeneration, J. Neurosci., 2009, vol. 29, no. 4, pp. 951963, .https://doi.org/10.1523/JNEUROSCI.2582-08.2009

35. Kadir, R., Harel, T., Markus, B., Perez, Y., Bakhrat, A., Cohen, I., Volodarsky, M., Feintsein-Linial, M., Chervinski, E., Zlotogora, J., Sivan, S., Birnbaum, R. Y., Abdu, U., Shalev, S., and Birk, O., S. ALFY-controlled DVL3 autophagy regulates Wnt signaling, determining human brain size, PLoS Genet., 2016. https://doi.org/10.1371/journal.pgen.1005919

36. Pei, Z., Oey, N., Zuidervaart, M., Jia, Z., Li, Y., Steinberg, S., Smith, K., and Watkins, P., The acyl-CoA synthetase bubblegum (lipidosin): further characterization and role in neuronal fatty acid beta-oxidation, J. Biol. Chem., 2003, vol. 278, no. 47, pp. 4707047078.

37. Sivachenko, A., Gordon, H., Kimball, S., Gavin, E., Bonkowsky, J., and Letsou, A., Neurodegeneration in a Drosophila model of drenoleukodystrophy: the roles of the Bubblegum and Double bubble acyl-CoA synthetases, Dis. Model., 2016, vol. 9, no. 4, pp. 377387. https://doi.org/10.1242/dmm.022244

38. Asheuer, M., Bieche, I., Laurendeau, I., Moser, A., Hainque, B., Vidaud, M., Aubourg, P., Decreased expression of ABCD4 and BG1 genes early in the pathogenesis of X-linked adrenoleukodystrophy, Hum. Mol. Genet., 2005, vol. 14, pp. 12931303.

39. Conway, S., Sansone, C., Benske, A., Kentala, K., Billen, J., Vanden Broeck J., and Blumenthal, E., Pleiotropic and novel phenotypes in the Drosophila gut caused by mutation of drop-dead, J. Insect. Physiol., 2018, vol. 105, pp. 7684. https://doi.org/10.1016/j.jinsphys.2018.01.007

40. Freeman, M., Dobritsa, A., Gaines, P., Segraves, W., and Carlson, J., The dare gene: steroid hormone production, olfactory behavior, and neural degeneration in Drosophila,Development, 1999, vol. 126, no. 20, pp. 45914602.

41. Paul, A., Drecourt, A., Petit, F., Deguine, D.D., Vasnier, C., Oufadem, M., Masson, C., Bonnet, C., Masmoudi, S., Mosnier, I., Mahieu, L., Bouccara, D., and 16 others, FDXR mutations cause sensorial neuropathies and expand the spectrum of mitochondrial Fe-S-synthesis diseases, Am. J. Hum. Genet., 2017, vol. 101, pp. 630637.

42. Roos, J., Hummel, T., Ng. N., Klambt, C., and Davis, G., Drosophila Futsch regulates synaptic microtubule organization and is necessary for synaptic growth, Neuron, 2000, vol. 26, no 2, pp. 371382.

43. Brazill, J., Cruz, B., Zhu, Y., and Zhai, R., Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy, Dis. Model Mech., 2018, vol. 11, no. 6, pii: dmm032938. https://doi.org/10.1242/dmm.032938

44. Halpain, S. and Dehmelt, L., The MA P1 family of microtubule-associated proteins, Genome Biol., 2006, vol. 7, no. 6, p. 224. https://doi.org/10.1186/gb-2006-7-6-224

45. Cook, M., Bolkan, B., and Kretzschmar, D., Increased actin polymerization and stabilization interferes with neuronal function and survival in the AMPKγ mutant Loechrig, PLoS One, 2014, vol. 9, no. 2, e89847. https://doi.org/10.1371/journal.pone.0089847

46. Morita, H., Rehm, H.L., Menesses, A., McDonough, B., Roberts, A.E., Kucherlapati, R., Towbin, J.A., Seidman, J.G., Seidman, C.E. Shared genetic causes of cardiac hypertrophy in children and adults, New Eng. J. Med., 2008, vol. 358, pp. 18991908.

47. Botella, J., Ulschmid, J., Gruenewald, C., Moehle, C., Kretzschmar, D., Becker, K., and Schneuwly, S., The Drosophila carbonyl reductase sniffer prevents oxidative stress-induced neurodegeneration, Curr. Biol., 2004, vol. 14, no. 9, pp. 782786.

48. Boynton, T. and Shimkets, L., Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are cardiolipin phospholipases, Genes Dev., 2015, vol. 29, no. 18, pp. 19031914, https://doi.org/10.1101/gad.268482.115

49. Skorczyk-Werner, A., Pawłowski, P., Michalczuk, M., Warowicka, A., Wawrocka, A., Wicher, K., Bakunowicz-Łazarczyk, A., and Krawczyński, M., Fundus albipunctatus: review of the literature and report of a novel RDH5 gene mutation affecting the invariant tyrosine (p.Tyrl75Phe), Appl. Genet., 2015, vol. 56, no. 3, pp. 317327. https://doi.org/10.1007/sl3353-015-0281-x

50. Celotto, A., Liu, Z., Vandemark, A., and Palladino, M., A novel Drosophila SOD2 mutant demonstrates a role for mitochondrial ROS in neurodevelopment and disease, Brain Behav., 2012, vol. 2, no 4, pp. 424434. https://doi.org/10.1002/brb3.73

51. Vitushynska, M.V., Matiytsiv, N.P., and Chernyk, Y., Sensitivity to the oxidative stress conditions lifespan and neurodegenerative changes in the brain structure of Drosophila melanogaster superoxide dismutase mutants, Visn. Lviv Univ.,Ser. Biol., 2013, vol. 62, pp. 108116.

52. De Rose, F., Marotta, R., Talani, G., Catelani, T., Solari, P., Poddighe, S., Borghero, G., Marrosu, F., Sanna, E., Kasture, S., Acquas, E., and Liscia, A., Differential effects of phytotherapic preparations in the hSODl Drosophila melanogaster model of ALS, Sci. Rep., 2017, vol. 7. https://doi.org/10.1038/srep41059

53. Hebbar, S., Khandelwal, A., Jayashree, R., Hindle, S., Chiang, Y., Yew, J., Sweeney, S., and Schwudke, D., Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders, Mol. Biol. Cell, 2017, vol. 8, no. 26, pp. 37283740. https://doi.org/10.1091/mbc.E16-09-0674

54. Miihlig-Versen, M., da Cruz, A., Tschäpe, J., Moser, M., Biittner, R., Athenstaedt, K., Glynn, P., and Kretzschmar, D., Loss of Swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila,J. Neurosci., 2005, vol. 25, no. 11, pp. 28652873.

55. Dutta, S., Rieche, F., Eckl, N., Duch, C., and Kretzschmar, D., Glial expression of Swiss cheese (SWS), the Drosophila orthologue of neuropathy target esterase (NTE), is required for neuronal ensheathment and function, Dis. Model Mech., 2016, vol. 9, no. 3, pp. 283294. https://doi.org/10.1242/dmm.022236

56. Ryabova, E., Matiytsiv, N., Trush, O., Mohylyak, I., Kislik, G., Melentev, P., and Sarantseva, S., Swiss cheese, Drosophila ortholog of hereditary spastic paraplegia gene NTE, maintains neuromuscular junction development and microtubule network, in Drosophila melanogasterModel for Recent Advances in Genetics and Therapeutics, Perveen, F.K., Ed., InTech, 2018. https://doi.org/10.5772/intechopen.73077

57. Crowther, D., Kinghorn, K., Miranda, E., Page, R., Curry, J., Duthie, F., Gubb, D., and Lomas, D., Intraneuronal Abeta, non-amyloid aggregates and neurodegeneration in a Drosophila model of Alzheimers disease, Neuroscience, 2005, vol. 132, pp. 123135.

58. Singh, S., Srivastav, S., Yadav, A., and Srikrishna, S., Knockdown of APPL mimics transgenic Ap induced neuro-degenerative phenotypes in Drosophila,Neurosci. Lett., 2017, vol. 648, pp. 813. https://doi.org/10.1016/j.neulet.2017.03.030

59. Luheshi, L., Tartaglia, G., Brorsson, A., Pawar, A., Watson, I., Chiti, F., Vendruscolo, M., Lomas, D., Dobson, C., and Crowther, D., Systematic in vivo analysis of the intrinsic determinants of amyloid beta pathogenicity, PLoS Biol., 2007. doi.org/https://doi.org/10.1371/journal.pbio.0050290

60. Saburova, E., Vasiliev, A., Kravtsova, V., Ryabova, E., Zefirov, A., Bolshakova, O., Sarantseva, S., and Krivoi, I., Human APP gene expression alters active zone distribution and spontaneous neurotransmitter release at the Drosophila larval neuromuscular junction, Neural. Plast., 2017. https://doi.org/10.1155/2017/9202584

61. Wentzell, J., Bolkan, B., Carmine-Simmen, K., Swanson, T., Musashe, D., and Kretzschmar, D., Amyloid precursor proteins are protective in Drosophila models of progressive neurodegeneration, Neurobiol. Dis., vol. 46, no. 1, pp. 7887. https://doi.org/10.1016/j.nbd.2011.12.047

62. Seidner, G., Ye, Y., Faraday, M., Alvord, W., and Fortini, M., Modeling clinically heterogeneous presenilin mutations with transgenic Drosophila,Curr. Biol., 2006, vol. 16, pp. 10261033.

63. Kang, J., Shin, S., Perrimon, N., and Shen, J., An evolutionarily conserved role of presenilin in neuronal protection in the aging Drosophila brain, Genetics, 2017, vol. 206, no. 3, pp. 14791493. https://doi.org/10.1534/genetics.116.196881

64. Chee, F., Mudher, A., Cuttle, M., Newman, T., MacKay, D., Lovestone, S., and Shepherd, D., Overexpression of tau results in defective synaptic transmission in Drosophila neuromuscular junctions, Neurobiol. Dis., 2005, vol. 20, pp. 918928.

65. Gorsky, M., Burnouf, S., Sofola-Adesakin, O., Dols, J., Augustin, H., Weigelt, C., Grönke, S., and Partridge, L., Pseudoacetylation of multiple sites on human Tau proteins alters Tau phosphorylation and microtubule binding, and ameliorates amyloid beta toxicity, Sci. Rep., 2017, vol. 7. no 1, p. 9984. https://doi.org/10.1038/s41598-017-10225-0

66. Talmat-Amar, Y., Arribat, Y., and Parmentier, M., Vesicular axonal transport is modified in vivo by Tau deletion or overexpression in Drosophila, Int. J. Mol. Sci., 2018, vol. 19, no 3, https://doi.org/10.3390/ijms19030744

67. Auluck, P., and Bonini, N., Pharmacological prevention of Parkinson disease in Drosophila,Nat. Med., 2002, vol. 8, pp. 11851186.

68. Mohite, G., Dwivedi, S., Das, S., Kumar, R., Paluri, S., Mehra, S., Ruhela, N.,S., Jha, N., and Maji, S., Parkinsons disease associated α-synuclein familial mutants promote dopaminergic neuronal death in Drosophila melanogaster,ACS Chem. Neurosci., 2018, vol. 9, no. 11, pp. 26282638. https://doi.org/10.1021/cschemneuro.8b00107

69. Sang, T., Chang, H., Lawless, G., Ratnaparkhi, A., Mee, L., Ackerson, L., Maidment, N., Krantz, D., and Jackson, G., A Drosophila model of mutant human parkin-induced toxicity demonstrates selective loss of dopaminergic neurons and dependence on cellular dopamine, J. Neurosci., 2007, vol. 27, pp. 981992.

70. Cornelissen, T., Vilain, S., Vints, K., Gounko, N., Verstreken, P., and Vandenberghe, W., Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila,Elife, 2018, vol. 9, no. 7. https://doi.org/10.7554/eLife.35878

71. Zhuang, N., Li, L., Chen, S., and Wang, T., PINK1-dependent phosphorylation of PINK1 and Parkin is essential for mitochondrial quality control, Cell Death Dis., 2016, vol. 7, no. 12. https://doi.org/10.1038/cddis.2016.396

72. Gunawardena, S., Her, L., Brusch, R., Laymon, R., Niesman, I., Gordesky-Gold, B., Sintasath, L., Bonini, N., and Goldstein, L., Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila,Neuron, 2003, vol. 40, pp. 2540.

73. Calpena, E., Lopez Del Amo, V., Chakraborty, M., Llamusi, B., Artero, R., Espinos, C., and Galindo, M., The Drosophila junctophilin gene is functionally equivalent to its four mammalian counterparts and is a modifier of a Huntingtin poly-Q expansion and the Notch pathway, Dis. Model. Mech., 2018, vol. 11, no 1. https://doi.org/10.1242/dmm.029082

74. Weiss, K., and Littleton, J., Characterization of axonal transport defects in Drosophila Huntingtin mutants, J. Neurogenet., 2016, vol. 30, pp. 21221.

75. Babcock, D. and Ganetzky, B., Transcellular spreading of huntingtin aggregates in the Drosophila brain, Proc. Natl. Acad. Sci. U. S. A., 2015, vol. 112, no. 39. https://doi.org/10.1073/pnas.1516217112

76. Watson, M., Lagow, R., Xu, K., Zhang, B., and Bonini, N., A Drosophila model for amyotrophic lateral sclerosis reveals motor neuron damage by human SOD1, J. Biol. Chem., 2008, vol. 283, pp. 2497224981.

77. Cummings, J., Lee, G., Ritter, A., and Zhong, K., Alzheimers disease drug development pipeline, Alzheimers Dement. (NY), 2018, vol. 4, pp. 195214.https://doi.org/10.1016/j.trci.2018.03.009

78. Fernandez-Funez, P., de Mena, L., and Rincon-Limas, D.E., Modeling the complex pathology of Alzheimers disease in Drosophila, Exp. Neurol., 2015, vol. 274, pt. A, pp. 5871.

79. Chatterjee, S., Sang, T., Lawless, G., and Jackson, G., Dissociation of tau toxicity and phosphorylation: role of GSK-3beta, MARK and Cdk5 in a Drosophila model, Hum. Mol. Genet., 2009, vol. 18, no 1, pp. 164177.

80. Kosmidis, S., Grammenoudi,S., Papanikolopoulou, K., and Skoulakis, E., Differential effects of tau on the integrity and function of neurons essential for learning in Drosophila,J. Neurosci., 2010, vol. 30, no. 2, pp. 464477.

81. Frost B., Hemberg M., Lewis J., Feany M.B., Tau promotes neurodegeneration through global chromatin relaxation, Nat. Neurosci., 2014, vol. 17, no. 3, pp. 357366.

82. Cowan, C., Bossing, T., Page, A., Shepherd, D., and Mudher, A., Soluble hyperphosphorylated tau causes micro-tubule breakdown and functionally compromises normal tau in vivo, Acta Neuropathol., 2010, vol. 120, no. 5, pp. 593604.

83. Cacabelos, R., Parkinsons disease: from pathogenesis to pharmacogenomics, Int. J. Mol. Sci., 2017, vol. 18, no. 3. https://doi.org/10.3390/ijms18030551

84. Ishizawa, T., Mattila, P., Davies, P., Wang, D., and Dickson, D., Colocalization of tau and alpha-synuclein epitopes in Lewy bodies, J. Neuropathol. Exper. Neurol., 2003, vol. 62, no. 4, pp. 389397.

85. Michel, P., Hirsch, E., and Hunot, S., Understanding dopaminergic cell death pathways in Parkinson disease, Neuron, 2016, vol. 90, no 4, pp. 675669.

86. Shulman, J. and De Jager, PL., Evidence for a common pathway linking neurodegenerative disease, Nat. Genet., 2009, vol. 41, no. 12, pp. 12611262.

87. Steffan, J., Bodai, L., Pallos, J., Poelman, M., McCampbell, A., Apostol, B.L., Kazantsev, A., Schmidt, E., Zhu, Y., Greenwald, M., Kurokawa, R., Housman, D., Jackson, G., Marsh, J., Thompson, L., Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila,Nature, 2001, vol. 413, no. 6857, pp. 739743.

88. Casci, I., and Pandey, U., A fruitful endeavor: modeling ALS in the fruit fly, Brain Res., 2015, vol. 1607, pp. 4774.

89. Nassel, D., Substrates for neuronal cotransmission with neuropeptides and small molecule neurotransmitters in Drosophila,Front. Cell Neurosci., 2018. https://doi.org/10.3389/fncel.2018.00083

90. Chad, M., Artymovych, N., Makarenko, O., and Matiytsiv, N., Effects of mitochondrin-2 on the dynamics of degeneration of brain tissues in Drosophila with an altered function of the swiss cheese gene, Neurophysiology, 2014, vol. 6, pp. 519524.

91. Agrell, I. and Lundquist, A. Physiological and biochemical changes during insect development; in The Physiology of Insecta, Rockstein, M., Ed., New York: Academic Press, 1973, vol. 1, pp. 159233.

92. Nichols, C., Ronesi, J., Pratt, W., and Sanders-Bush, E., Hallucinogens and Drosophila: linking serotonin receptor activation to behavior, Neuroscience, 2002, vol. 115, pp. 979984.

93. Wang, L., Hagemann, T., Messing A., and Feany, M., An in vivo pharmacological screen identifies cholinergic signaling as a therapeutic target in glial-based nervous system disease, J. Neurosci., 2016, vol. 36, no. 5, pp. 14451455. https://doi.org/10.1523/JNEUROSCI.0256-15.2016

94. Dzitoyeva, S., Dimitrijevic, N., and Manev, H., Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence, Proc. Natl. Acad. Sci. U. S. A., 2003, vol. 100, pp. 54855490.

95. Uttara, B., Singh, A., Zamboni, P., and Mahajan, R.T., Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options, Curr. Neuropharmacol., 2009, vol. 7, pp. 6574.

96. Angelova, P.R. and Abramov, A.Y., Role of mitochondrial ROS in the brain: from physiology to neurodegeneration, FEBS Lett., 2018, vol. 592, no. 5, pp. 692702. https://doi.org/10.1002/1873-3468.12964

97. Oswald, M.C.W., Garnham, N., Sweeney, S.T., and Landgraf, M., Regulation of neuronal development and function by ROS, FEBS Lett., 2018, vol. 592, no. 5, pp. 679691. https://doi.org/10.1002/1873-3468.12972

98. Poljsak, B., Šuput, D., and Milisav, I., Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants, Oxid. Med. Cell. Longev., 2013, article ID 956792.

99. Mathur, S., and Hoskins, C., Drug development: lessons from nature, Biomed. Rep., 2017, vol. 6, pp. 612614.

100. Harvey, A., Edrada-Ebel, R., and Quinn, R., The reemergence of natural products for drug discovery in the genomics era, Nat. Rev. Drug Discov., 2015, vol. 14, pp. 111129.

101. Lakkappa, N., Krishnamurthy, P., M D P., Hammock, B., and Hwang, S., Soluble epoxide hydrolase inhibitor, APAU, protects dopaminergic neurons against rotenone induced neurotoxicity: implications for Parkinsons disease, Neurotoxicology, 2018, vol. 70, pp. 135145. https://doi.org/10.1016/j.neuro.2018.11.010

102. Siddique, Y., Naz, F., and Jyoti S., Effect of capsaicin on the oxidative stress and dopamine content in the transgenic Drosophila model of Parkinsons disease, Acta Biol. Hung., 2018, vol. 69, no. 2, pp. 115124. doi 10.1556/018.69.2018.2.1

103. Phom, L., Achumi, B., Alone, D., Muralidhara, and Yenisetti, S., Curcumins neuroprotective efficacy in Drosophila model of idiopathic Parkinsons disease is phase specific: implication of its therapeutic effectiveness, Rejuvenation Res., 2014, vol. 7, no. 6, pp. 481489. https://doi.org/10.1089/rej.2014.1591

104. Nguyen, T., Vuu, M., Huynh, M., Yamaguchi, M., Tran, L., and Dang, T., Curcumin effectively rescued Parkinsons disease-like phenotypes in a novel Drosophila melanogaster model with dUCH knockdown, Oxid. Med. Cell Longev., 2018. https://doi.org/10.1155/2018/2038267

105. Chongtham, A. and Agrawal, N., Curcumin modulates cell death and is protective in Huntingtons disease model, Sci. Rep., 2016, vol. 6, p. 18736. https://doi.org/10.1038/srep18736

106. Rao, S., Muralidhara, Yenisetti, S., and Rajini, P., Evidence of neuroprotective effects of saffron and crocin in a Drosophila model of parkinsonism, Neurotoxicology, 2016, vol. 52, pp. 230242. https://doi.org/10.1016/j.neuro.2015.12.010

107. Varga, J., Dér, N., Zsindely, N., and Bodai, L., Green tea infusion alleviates neurodegeneration induced by mutant Huntingtin in Drosophila,Nutr. Neurosci., 2018. https://doi.org/10.1080/1028415X.2018.1484021

108. Ng, C., Basil, A., Hang, L., Tan, R., Goh, K., ONeill, S., Zhang, X., Yu, F., and Lim, K., Genetic or pharmacological activation of the Drosophila PGC-1α ortholog spargel rescues the disease phenotypes of genetic models of Parkinsons disease, Neurobiol. Aging, 2017, vol. 55, pp. 3337. https://doi.org/10.1016/j.obiolaging.2017.03.017

109. Abolaji, A., Adedara, A., Adie, M., Vicente-Crespo, M., and Farombi, E., Resveratrol prolongs lifespan and improves 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced oxidative damage and behavioural deficits in Drosophila melanogaster,Biochem. Biophys. Res. Commun., 2018, vol. 503, no. 2, pp. 10421048. https://doi.org/10.1016/j.bbrc.2018.06.114

110. Wu, Z., Wu, A., Dong, J., Sigears, A., and Lu, B., Grape skin extract improves muscle function and extends lifespan of a Drosophila model of Parkinsons disease through activation of mitophagy, Exp. Gerontol., 2018, vol. 113, pp. 1017. https://doi.org/10.1016/j.exger.2018.09.014

111. Büttner, S., Broeskamp, F., Sommer, C., Markaki, M., Habernig, L., Alavian-Ghavanini, A., Carmona-Gutierrez, D., Eisenberg, T., Michael, E., Kroemer, G., Tavernarakis, N., Sigrist, S., and Madeo, F., Spermidine protects against α-synuclein neurotoxicity, Cell Cycle, 2014, vol. 13, no. 24, pp. 39033908. https://doi.org/10.4161/15384101.2014.973309

112. Jahromi, S., Haddadi, M., Shivanandappa, T., and Ramesh, S., Attenuation of neuromotor deficits by natural antioxidants of Decalepis hamiltonii in transgenic Drosophila model of Parkinsons disease, Neuroscience, 2015, vol. 293, pp. 136150.

113. Briffa, M., Ghio, S., Neuner, J., Gauci, A.J., Cacciottolo, R., Marchal, C., Caruana, M., Cullin, C., Vassallo, N., Cauchi, R., Extracts from two ubiquitous Mediterranean plants ameliorate cellular and animal models of neurodegenerative proteinopathies, Neurosci. Lett., 2017, vol. 638, pp. 1220.

114. Burnstock, G., Do some nerve cells release more than one transmitter?, Neuroscience, 1976, vol. 1, pp. 239248.

115. Vaaga, C., Borisovska, M., and Westbrook, G., Dual-transmitter neurons: functional implications of co-release and co-transmission, Curr. Opin. Neurobiol., 2014, vol. 29, pp. 2532. https://doi.org/10.1016/j.conb.2014.04.010

116. Nusbaum, M., and Blitz, D., Neuropeptide modulation of microcircuits, Curr. Opin. Neurobiol., 2012, vol. 22, pp. 592601. https://doi.org/10.1016/j.conb.2012.01.003

117. Glantz, R., Miller, C., and Nssel, D., Tachykinin-related peptide and GABA-mediated presynaptic inhibition of crayfish photoreceptors, J. Neurosci., 2000, vol. 20, pp. 17801790.

118. Nässel, D., Neuropeptide signaling near and far: how localized and timedis the action of neuropeptides in brain circuits?, Invert. Neurosci., 2009, vol. 9, pp. 5775. https://doi.org/10.1007/s10158-009-0090-1

119. Veenstra, J., Agricola, H., and Sellami, A., Regulatory peptides in fruit fly midgut, Cell Tissue Res., 2008, vol. 334, pp. 499516. https://doi.org/10.1007/s00441-008-0708-3

120. Zandawala, M., Marley, R., Davies, S. A., and Nässel, D., Characterization of a set of abdominal neuroendocrine cells that regulate stress physiology using colocalized diuretic peptides in Drosophila,Cell Mol. Life. Sci., 2018, vol. 75, pp. 1099115. https://doi.org/10.1007/s00018-017-2682-y

121. Sharma, H., Sharma, A., Mössler, H., Muresanu, D., Neuroprotective effects of cerebrolysin, a combination of different active fragments of neurotrophic factors and peptides on the whole body hyperthermia-induced neurotoxicity: Modulatory roles of comorbidity factors and nanoparticle intoxication, Int. Rev. Neurobiol., 2012, vol. 102, p. 249.

122. Makarenko, A., Kulchikov, A., and Morozov, S., Medicinal preparation for treatment of hypoxic and toxic-mitochondrial abnormalities and the techniquefor its synthesis, Inventors Certificate no. 2405558 Russia, Published December 10, 2010, Byull. Izobret., 2010, no. 23.

Copyright© ICBGE 2002-2021 Coded & Designed by Volodymyr Duplij Modified 26.10.21