An assessment of the translational relevance of Drosophila in drug discovery

References

• Bellen HJ, Tong C, Tsuda H. 100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future. Nat Rev Neurosci. 2010;11(7): 514–522. PubMed PMID: 20383202.
   PubMed Web of Science ®Google Scholar
• Adams MD, Celniker SE, Holt RA, et al. The genome sequence of Drosophila melanogaster. Science. 2000;287(5461):2185–2195. PubMed PMID: 10731132.
   PubMed Web of Science ®Google Scholar
• Chien S, Reiter LT, Bier E, et al. Homophila: human disease gene cognates in Drosophila. Nucleic Acids Res. 2002;30(1): 149–151. PubMed PMID: 11752278.
   PubMed Web of Science ®Google Scholar
• Perrimon N, Pitsouli C, Shilo B-Z. Signaling mechanismscontrolling cell fate and embryonic patterning. Cold Spring Harb Perspect Biol. 2012;4:a005975.
   PubMed Web of Science ®Google Scholar
• Angeles D, Ho P, Dymock B, et al. Antioxidants inhibit neuronal toxicity in Parkinson’s disease-linked LRRK2. Ann Clin Transl Neurol. 2016;3:288–294.
   PubMed Web of Science ®Google Scholar
• Pandey UB, Nichols CD. Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol Rev. 2011;63(2): 411–436. PubMed PMID: 21415126.
   PubMed Web of Science ®Google Scholar
• Fernandez-Hernandez I, Scheenaard E, Pollarolo G, et al. The translational relevance of Drosophila in drug discovery. EMBO Rep. 2016;17(4): 471–472. PubMed PMID: 26882560.
   PubMed Web of Science ®Google Scholar
• Quraishe S, Cowan CM, Mudher A. NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy. Mol Psychiatry. 2013;18(7):834–842. PubMed PMID: 23587881; PubMed Central PMCID: PMC3690421.
   PubMed Web of Science ®Google Scholar
• St Johnston D. The art and design of genetic screens: Drosophila melanogaster. Nat Rev Genet. 2002;3(3): 176–188. PubMed PMID: 11972155.
   PubMed Web of Science ®Google Scholar
• Şentürk M, Bellen HJ. Genetic strategies to tackle neurological diseases in fruit flies. Curr Opin Neurobiol. 2018;50:24–32. PubMed PMID: 29128849.
   PubMed Web of Science ®Google Scholar
• Caygill EE, Brand AH. The GAL4 system: a versatile system for the manipulation and analysis of gene expression. Methods Mol Biol. 2016;1478:33–52. PubMed PMID: 27730574.
   PubMedGoogle Scholar
• Jenett A, Rubin GM, Ngo TT, et al. A GAL4-driver line resource for Drosophila neurobiology. Cell Rep. 2012;2(4):991–1001. PubMed PMID: 23063364.
   PubMed Web of Science ®Google Scholar
• Matthews KA, Kaufman TC, Gelbart WM. Research resources for Drosophila: the expanding universe. Nat Rev Genet. 2005;6:170–193.
   Web of Science ®Google Scholar
• Roman G. The genetics of Drosophila transgenics. BioEssays. 2004;26(11):1243–1253.
   PubMed Web of Science ®Google Scholar
• Papanikolopoulou K, Skoulakis EM. Temporally distinct phosphorylations differentiate Tau-dependent learning deficits and premature mortality in Drosophila. PubMed PMID: 25524708 Hum Mol Genet. 2015;247:2065–2077.
   PubMed Web of Science ®Google Scholar
• Warr C, Shaw K, Azim A, et al. Using mouse and drosophila models to investigate the mechanistic links between diet, obesity, type II diabetes, and cancer. Int J Mol Sci. 2018 Dec 18;19(12):pii: E4110.
   PubMed Web of Science ®Google Scholar
• Enomoto M, Siow C, Igaki T. Drosophila as a cancer model. Adv Exp Med Biol. 2018;1076:173–194.
   PubMed Web of Science ®Google Scholar
• Venken KJT, Simpson JH, Bellen HJ. Genetic manipulation of genes and cells in the nervous system of the fruit fly. Neuron. 2011;72:202–230.
   PubMed Web of Science ®Google Scholar
• Fortini ME, Skupski MP, Boguski MS, et al. A survey of human disease gene counterparts in the Drosophila genome. J Cell Biol. 2000;150:F23–F30.
   PubMed Web of Science ®Google Scholar
• Bellen HJ, Yamamoto S. Morgan’s legacy: fruit flies and the functional annotation of conserved genes. Cell. 2015;163:12–14.
   PubMed Web of Science ®Google Scholar
• Boulianne GL, Livne-Bar I, Humphreys JM, et al. Cloning and characterization of the Drosophila presenilin homologue. Neuroreport. 1997;8(4):1025–1029. PubMed PMID: 9141085.
   PubMed Web of Science ®Google Scholar
• Hong CS, Koo EH. Isolation and characterization of Drosophila presenilin homolog. Neuroreport. 1997;8(3): 665–668. PubMed PMID: 9106743.
   PubMed Web of Science ®Google Scholar
• Ye Y, Lukinova N, Fortini ME. Neurogenic phenotypes and altered notch processing in Drosophila presenilin mutants. Nature. 1999;3986727:525–529. PubMed PMID: 10206647.
   PubMed Web of Science ®Google Scholar
• Shulman JM. Drosophila and experimental neurology in the post-genomic era. Exp Neurol. 2015;274:4–13.
   PubMed Web of Science ®Google Scholar
• Shulman JM, Imboywa S, Giagtzoglou N, et al. Functional screening in Drosophila identifies Alzheimer’s disease susceptibility genes and implicates Tau-mediated mechanisms. Hum Mol Genet. 2014;23(4):870–877. PubMed PMID: 24067533.
   PubMed Web of Science ®Google Scholar
• Dutta S, Rieche F, Eckl N, et al. 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;9:283–294.
   PubMed Web of Science ®Google Scholar
• Rubin G, Yandell M, Wortman J, et al. Comparative genomics of the eukaryotes. Science. 2000;287(5461):2204–2215.
   PubMed Web of Science ®Google Scholar
• Hall D, Berry-Kravis E. Fragile X syndrome and fragile X-associated tremor ataxia syndrome. Handb Clin Neurol. 2018;147:377–391.
   PubMedGoogle Scholar
• Drozd M, Bardoni B, Capovilla M. Modeling Fragile X syndrome in Drosophila. Front Mol Neurosci. 2018 Apr 16;11:124.
   PubMed Web of Science ®Google Scholar
• Walker J, Gouzi J, Long J, et al. Genetic and functional studies implicate synaptic overgrowth and ring gland cAMP/PKA signaling defects in the Drosophila melanogaster neurofibromatosis-1 growth deficiency. PLoS Genet. 2013;9(11):e1003958.
   PubMed Web of Science ®Google Scholar
• Shulman J, Chipendo P, Chibnik L, et al. Functional screening of Alzheimer pathology genome-wide association signals in Drosophila. Am J Hum Genet. 2011;88(2):232–238.
   PubMed Web of Science ®Google Scholar
• Chapuis J, Hansmannel F, Gistelinck M, et al. Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology. Mol Psychiatry. 2013;18(11):1225–1234. Epub 2013/ 02/13. PubMed PMID: 23399914; PubMed Central PMCID: PMC3807661.
   PubMed Web of Science ®Google Scholar
• Moreau K, Fleming A, Imarisio S, et al. PICALM modulates autophagy activity and tau accumulation. Nat Commun. 2014;5:4998. PubMed PMID: 25241929; PubMed Central PMCID: PMC4199285.
   PubMed Web of Science ®Google Scholar
• Dourlen P, Fernandez-Gomez FJ, Dupont C, et al. Functional screening of Alzheimer risk loci identifies PTK2B as an in vivo modulator and early marker of Tau pathology. Mol Psychiatry. 2017;22(6):874–883. PubMed PMID: 27113998; PubMed Central PMCID: PMCPMC5444024.
   PubMed Web of Science ®Google Scholar
• Williams DW, Tyrer M, Shepherd D. Tau and tau reporters disrupt central projections of sensory neurons in Drosophila. J Comp Neurol. 2000;428(4): 630–640. PubMed PMID: 11077417.
   PubMed Web of Science ®Google Scholar
• Wittmann CW, Wszolek MF, Shulman JM, et al. Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science . 2001;293(5530):711–714. PubMed PMID: 11408621. .
   PubMed Web of Science ®Google Scholar
• Kosmidis S, Grammenoudi S, Papanikolopoulou K, et al. Differential effects of Tau on the integrity and function of neurons essential for learning in Drosophila. J Neurosci. 2010;30:464–477.
   PubMed Web of Science ®Google Scholar
• Sealey MA, Vourkou E, Cowan CM, et al. Distinct phenotypes of three-repeat and four-repeat human Tau in a transgenic model of tauopathy. Neurobiol Dis. 2017;105:74–83. PubMed PMID: 28502805.
   PubMed Web of Science ®Google Scholar
• Chee F, Mudher A, Newman TA, et al. Overexpression of tau results in defective synaptic transmission in Drosophila neuromuscular junctions. PubMed PMID: 16417489 Biochem Soc Trans. 2006;34Pt 1:88–90.
   PubMedGoogle Scholar
• Chouhan AK, Guo C, Hsieh YC, et al. Uncoupling neuronal death and dysfunction in Drosophila models of neurodegenerative disease. Acta Neuropathol Commun. 2016;4(1):62. PubMed PMID: 27338814.
   PubMedGoogle Scholar
• Cowan CM, Chee F, Shepherd D, et al. Disruption of neuronal function by soluble hyperphosphorylated tau in a Drosophila model of tauopathy. PubMed PMID: 20298222 Biochem Soc Trans. 2010;382:564–570.
   PubMedGoogle Scholar
• Wang T, Montell C. Phototransduction and retinal degeneration in Drosophila. Pflugers Arch. 2007;454(5): 821–847. PubMed PMID: 17487503.
   PubMed Web of Science ®Google Scholar
• Ali YO, Ruan K, Zhai RG. NMNAT suppresses tau-induced neurodegeneration by promoting clearance of hyperphosphorylated tau oligomers in a Drosophila model of tauopathy. Hum Mol Genet. 2012;21(2): 237–250. PubMed PMID: 21965302.
   PubMed Web of Science ®Google Scholar
• Khurana V, Elson-Schwab I, Fulga TA, et al. Lysosomal dysfunction promotes cleavage and neurotoxicity of tau in vivo. PLoS Genet. 2010;6(7):e1001026. PubMed PMID: 20664788.
   PubMed Web of Science ®Google Scholar
• Khurana V, Lu Y, Steinhilb ML, et al. TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model. Curr Biol. 2006;16(3): 230–241. PubMed PMID: 16461276.
   PubMed Web of Science ®Google Scholar
• Papanikolopoulou K, Kosmidis S, Grammenoudi S, et al. Phosphorylation differentiates tau-dependent neuronal toxicity and dysfunction. PubMed PMID: 20658989 Biochem Soc Trans. 2010;384:981–987.
   PubMedGoogle Scholar
• Povellato G, Tuxworth RI, Hanger DP, et al. Modification of the Drosophila model of in vivo Tau toxicity reveals protective phosphorylation by GSK3beta. PubMed PMID: 24429107; PubMed Central PMCID: PMC3892155 Biol Open. 2014;31:1–11.
   PubMed Web of Science ®Google Scholar
• Şahin A, Held A, Bredvik K, et al. Human SOD1 ALS mutations in a Drosophila knock-in model cause severe phenotypes and reveal dosage-sensitive gain- and loss-of-function components. Genetics. 2017;205(2):707–723.
   PubMed Web of Science ®Google Scholar
• Gorsky M, Burnouf S, Sofola-Adesakin O, et al. Pseudo-acetylation of multiple sites on human Tau proteins alters Tau phosphorylation and microtubule binding, and ameliorates amyloid beta toxicity. Sci Rep. 2017;7(1):9984.
   PubMedGoogle Scholar
• Feany M, Bender W. A Drosophila model of Parkinson’s disease. Nature. 2000;404:394–398.
   PubMed Web of Science ®Google Scholar
• Ordonez D, Lee M, Feany M. α-synuclein induces mitochondrial dysfunction through spectrin and the actin cytoskeleton. Neuron. 2018;97(1):108–124.
   PubMed Web of Science ®Google Scholar
• Healy D, Falchi M, O’Sullivan S, et al. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson’s disease: a case-control study. Lancet Neurol. 2008;7:583–590.
   PubMed Web of Science ®Google Scholar
• Iijima K, Liu H, Chiang A, et al. Dissecting the pathological effects of human abeta40 and abeta42 in Drosophila: a potential model for Alzheimer’s disease. Proc Natl Acad Sci U S A. 2004;101(17):6623–6628.
   PubMed Web of Science ®Google Scholar
• O’Keefe L, Denton D. Using Drosophila models of amyloid toxicity to study autophagy in the pathogenesis of Alzheimer’s disease. Biomed Res Int. 2018 May 20;2018:5195416.
   PubMedGoogle Scholar
• Tsuda L, Lim Y. Alzheimer’s disease model system using Drosophila. Adv Exp Med Biol. 2018;1076:25–40.
   PubMed Web of Science ®Google Scholar
• Ambegaokar SS, Jackson GR. Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation. Hum Mol Genet. 2011;20(24): 4947–4977. PubMed PMID: 21949350.
   PubMed Web of Science ®Google Scholar
• Vossfeldt H, Butzlaff M, Prüssing K, et al. Large-scale screen for modifiers of ataxin-3-derived polyglutamine-induced toxicity in Drosophila. PLoS One. 2012;7(11):e47452.
   PubMed Web of Science ®Google Scholar
• Shulman JM, Feany MB. Genetic modifiers of tauopathy in Drosophila. Genetics. 2003;165(3):1233–1242. PubMed PMID: 14668378.
   PubMed Web of Science ®Google Scholar
• Martin I, Chittoor V. Parkinson disease: insect screens for PD therapies – keep the flies in. Nat Rev Neurol. 2016 Jun;12(6):318–319.
   PubMedGoogle Scholar
• Al-Ramahi I, Pérez A, Lim J, et al. dAtaxin-2 mediates expanded ataxin-1-induced neurodegeneration in a Drosophila model of SCA1. PLoS Genet. 2007;3(12):234.
   Web of Science ®Google Scholar
• Martín-Peña A, Rincón-Limas D, Fernandez-Fúnez P. Engineered Hsp70 chaperones prevent Aβ42-induced memory impairments in a Drosophila model of Alzheimer’s disease. Sci Rep. 2018;8(1):9915.
   PubMedGoogle Scholar
• Falzone TL, Gunawardena S, McCleary D, et al. Kinesin-1 transport reductions enhance human tau hyperphosphorylation, aggregation and neurodegeneration in animal models of tauopathies. Hum Mol Genet. 2010;19(22):4399–4408. PubMed PMID: 20817925.
   PubMed Web of Science ®Google Scholar
• Talmat-Amar Y, Arribat Y, Redt-Clouet C, et al. Important neuronal toxicity of microtubule-bound Tau in vivo in Drosophila. Hum Mol Genet. 2011;20(19):3738–3745. PubMed PMID: 21705366.
   PubMed Web of Science ®Google Scholar
• Papanikolopoulou K, Grammenoudi S, Samiotaki M, et al. Differential effects of 14-3-3 dimers on Tau phosphorylation, stability and toxicity in vivo. Hum Mol Genet. 2018;27(13):2244–2261.
   PubMed Web of Science ®Google Scholar
• Colodner KJ, Feany MB. Glial fibrillary tangles and jak/stat-mediated glial and neuronal cell death in a Drosophila model of glial tauopathy. J Neurosci. 2010;30(48):16102–16113. PubMed PMID: 21123557.
   PubMed Web of Science ®Google Scholar
• McGurk L, Berson A, Bonini NM. Drosophila as an in vivo model for human neurodegenerative disease. Genetics. 2015;201(2):377–402. PubMed PMID: 26447127.
   PubMed Web of Science ®Google Scholar
• Jackson GR, Wiedau-Pazos M, Sang TK, et al. Human wild-type tau interacts with wingless pathway components and produces neurofibrillary pathology in Drosophila. Neuron. 2002;34(4):509–519. PubMed PMID: 12062036.
   PubMed Web of Science ®Google Scholar
• Hewitt V, Whitworth A. Mechanisms of Parkinson’s disease: lessons from Drosophila. Curr Top Dev Biol. 2017;121:173–200.
   PubMed Web of Science ®Google Scholar
• Dias-Santagata D, Fulga TA, Duttaroy A, et al. Oxidative stress mediates tau-induced neurodegeneration in Drosophila. PubMed PMID: 17173140; PubMed Central PMCID: PMC1697799 J Clin Invest. 2007;1171:236–245.
   PubMed Web of Science ®Google Scholar
• Busser J, Geldmacher DS, Herrup K. Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer’s disease brain. J Neurosci. 1998;18(8): 2801–2807. PubMed PMID: 9525997.
   PubMed Web of Science ®Google Scholar
• Davis RL. Olfactory memory formation in Drosophila: from molecular to systems neuroscience. Annu Rev Neurosci. 2005;28:275–302.
   PubMed Web of Science ®Google Scholar
• Folwell J, Cowan CM, Ubhi KK, et al. Abeta exacerbates the neuronal dysfunction caused by human tau expression in a Drosophila model of Alzheimer’s disease. Exp Neurol. 2010;223(2):401–409. PubMed PMID: 19782075.
   PubMed Web of Science ®Google Scholar
• Lin C, Lin H, Chen M, et al. Lovastatin protects neurite degeneration in LRRK2-G2019S parkinsonism through activating the Akt/Nrf pathway and inhibiting GSK3β activity. Hum Mol Genet. 2016 May 15;25(10):1965–1978.
   PubMed Web of Science ®Google Scholar
• Burr A, Tsou W, Ristic G, et al. Using membrane-targeted green fluorescent protein to monitor neurotoxic protein-dependent degeneration of Drosophila eyes. J Neurosci Res. 2014;92(9):1100–1109.
   PubMed Web of Science ®Google Scholar
• Dourlen P. Identification of Tau toxicity modifiers in the drosophila eye. Methods Mol Biol. 2017;1523: 375–389. PubMed PMID: 27975266.
   PubMedGoogle Scholar
• Lőrincz P, Takáts S, Kárpáti M, et al. iFly: the eye of the fruit fly as a model to study autophagy and related trafficking pathways. Exp Eye Res. 2016;144:90–98.
   PubMed Web of Science ®Google Scholar
• Kumar JP. Building an ommatidium one cell at a time. Dev Dyn. 2012;241(1):136–149. PubMed PMID: 22174084.
   PubMed Web of Science ®Google Scholar
• Iyer J, Wang Q, Le T, et al. Quantitative assessment of eye phenotypes for functional genetic studies using drosophila melanogaster. G3 (Bethesda). 2017;6(5):1427–1437.
   Google Scholar
• Trotter MB, Stephens TD, McGrath JP, et al. The Drosophila model system to study tau action. Methods Cell Biol. 2017;141:259–286. PubMed PMID: 28882306.
   PubMed Web of Science ®Google Scholar
• Bolkan BJ, Kretzschmar D. Loss of Tau results in defects in photoreceptor development and progressive neuronal degeneration in Drosophila. Dev Neurobiol. 2014;74(12):1210–1225. PubMed PMID: 24909306.
   PubMed Web of Science ®Google Scholar
• Butzlaff M, Hannan SB, Karsten P, et al. Impaired retrograde transport by the dynein/dynactin complex contributes to Tau-induced toxicity. Hum Mol Genet. 2015;24(13):3623–3637. PubMed PMID: 25794683.
   PubMed Web of Science ®Google Scholar
• Lessing D, Bonini N. Polyglutamine genes interact to modulate the severity and progression of neurodegeneration in Drosophila. PLoS Biol. 2008;6(2):e29.
   PubMed Web of Science ®Google Scholar
• Sang T, Jackson G. Drosophila models of neurodegenerative disease. NeuroRx. 2005;3:438–446.
   Google Scholar
• Marcogliese P, Abuaish S, Kabbach G, et al. LRRK2(I2020T) functional genetic interactors that modify eye degeneration and dopaminergic cell loss in Drosophila. Hum Mol Genet. 2017;26(7):1247–1257.
   PubMed Web of Science ®Google Scholar
• Raghu P, Coessens E, Manifava M, et al. Rhabdomere biogenesis in Drosophila photoreceptors is acutely sensitive to phosphatidic acid levels. J Cell Biol. 2009;185(1):129–145. PubMed PMID: 19349583.
   PubMed Web of Science ®Google Scholar
• Arendt T, Stieler JT, Holzer M. Tau and tauopathies. PubMed PMID: 27615390 Brain Res Bull. 2016;126Pt 3:238–292.
   PubMed Web of Science ®Google Scholar
• Yeh PA, Chien JY, Chou CC, et al. Drosophila notal bristle as a novel assessment tool for pathogenic study of Tau toxicity and screening of therapeutic compounds. Biochem Biophys Res Commun. 2010;391(1):510–516. PubMed PMID: 19931224.
   PubMed Web of Science ®Google Scholar
• Mudher A, Shepherd D, Newman TA, et al. GSK-3beta inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila. Mol Psychiatry. 2004;9(5):522–530. PubMed PMID: 14993907.
   PubMed Web of Science ®Google Scholar
• Ubhi KK, Shaibah H, Newman TA, et al. A comparison of the neuronal dysfunction caused by Drosophila tau and human tau in a Drosophila model of tauopathies. PubMed PMID: 17636367 Invert Neurosci. 2007;73:165–171.
   PubMedGoogle Scholar
• Kosmidis S, Botella J, Mandilaras K, et al. Ferritin overexpression in Drosophila glia leads to iron deposition in the optic lobes and late-onset behavioral defects. Neurobiol Dis. 2011;43(1):213–219.
   PubMed Web of Science ®Google Scholar
• Khalil B, Cabirol-Pol M, Miguel L, et al. Enhancing mitofusin/marf ameliorates neuromuscular dysfunction in Drosophila models of TDP-43 proteinopathies. Neurobiol Aging. 2017;54:71–83.
   PubMed Web of Science ®Google Scholar
• Riemensperger T, Issa A, Pech U, et al. A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease. Cell Rep. 2013 Nov 27;5(4):952–960.
   PubMed Web of Science ®Google Scholar
• Talmat-Amar Y, Arribat Y, Parmentier ML. Vesicular axonal transport is modified in vivo by tau deletion or overexpression in Drosophila. Int J Mol Sci. 2018;19(3). PubMed PMID: 29509687.
   PubMed Web of Science ®Google Scholar
• Torroja L, Chu H, Kotovsky I, et al. Neuronal overexpression of APPL, the Drosophila homologue of the amyloid precursor protein (APP), disrupts axonal transport. Curr Biol. 1999;9:489–492.
   PubMed Web of Science ®Google Scholar
• Fernius J, Starkenberg A, Thor S. Bar-coding neurodegeneration: identifying subcellular effects of human neurodegenerative disease proteins using Drosophila leg neurons. Dis Model Mech. 2017;10:1027–1038.
   PubMed Web of Science ®Google Scholar
• Pitman J, DasGupta S, Krashes M, et al. There are many ways to train a fly. Fly (Austin). 2009;3(1):3–9.
   PubMed Web of Science ®Google Scholar
• Mershin A, Pavlopoulos E, Fitch O, et al. Learning and memory deficits upon TAU accumulation in Drosophila mushroom body neurons. Learn Mem. 2004;11(3):277–287. PubMed PMID: 15169857.
   PubMed Web of Science ®Google Scholar
• McGuire SE, Mao Z, Davis RL. Spatiotemporal gene expression targeting with the TARGET and gene-switch systems in Drosophila. Sci STKE. 2004;2004(220): pl6. PubMed PMID: 14970377.
   PubMedGoogle Scholar
• Ping Y, Hahm E, Waro G, et al. Linking aβ42-induced hyperexcitability to neurodegeneration, learning and motor deficits, and a shorter lifespan in an Alzheimer’s model. PLoS Genet. 2015;11(3):e1005025.
   PubMed Web of Science ®Google Scholar
• Iijima K, Chiang H, Hearn S, et al. Abeta42 mutants with different aggregation profiles induce distinct pathologies in Drosophila. PLoS One. 2008;3(2):e1703.
   PubMed Web of Science ®Google Scholar
• Santos A, Kanellopoulos A, Bagni C. Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach us. Learn Mem. 2014;21(10):543–555.
   PubMed Web of Science ®Google Scholar
• Guo H, Tong J, Hannan F, et al. A neurofibromatosis-1-regulated pathway is required for learning in Drosophila. Nature. 2000;403(6772):895–898.
   PubMed Web of Science ®Google Scholar
• Mansilla A, Chaves-Sanjuan A, Campillo N, et al. Interference of the complex between NCS-1 and Ric8a with phenothiazines regulates synaptic function and is an approach for fragile X syndrome. Proc Natl Acad Sci U S A. 2017;114(6):E999–E1008.
   PubMed Web of Science ®Google Scholar
• Rand MD. Drosophotoxicology: the growing potential for Drosophila in neurotoxicology. Neurotoxicol Teratol. 2010;32(1): 74–83. PubMed PMID: 19559084.
   PubMed Web of Science ®Google Scholar
• Mayer F, Mayer N, Chinn L, et al. Evolutionary conservation of vertebrate blood-brain barrier chemoprotective mechanisms in Drosophila. J Neurosci. 2009;29(11): 3538–3550. PubMed PMID: 19295159.
   PubMed Web of Science ®Google Scholar
• Stork T, Engelen D, Krudewig A, et al. Organization and function of the blood-brain barrier in Drosophila. J Neurosci. 2008;28(3): 587–597. PubMed PMID: 18199760.
   PubMed Web of Science ®Google Scholar
• Limmer S, Weiler A, Volkenhoff A, et al. The Drosophila blood-brain barrier: development and function of a glial endothelium. Front Neurosci. 2014;8:365.
   PubMed Web of Science ®Google Scholar
• Turrel O, Goguel V, Preat T. Drosophila neprilysin 1 rescues memory deficits caused by amyloid-β peptide. J Neurosci. 2017;37(43):10334–10345.
   PubMed Web of Science ®Google Scholar
• Beg T, Jyoti S, Naz F, et al. Protective effect of kaempferol on the transgenic Drosophila model of Alzheimer’s Disease. CNS Neurol Disord Drug Targets. 2018;17(6):421–429.
   PubMed Web of Science ®Google Scholar
• Cushman-Nick M, Bonini N, Shorter J. Hsp104 suppresses polyglutamine-induced degeneration post onset in a drosophila MJD/SCA3 model. PLoS Genet. 2013;9(9):e1003781.
   PubMed Web of Science ®Google Scholar
• Nelson V, Ali A, Dutta N, et al. Azadiradione ameliorates polyglutamine expansion disease in Drosophila by potentiating DNA binding activity of heat shock factor 1. Oncotarget. 2016 Nov 29;7(48):78281–78296.
   PubMedGoogle Scholar
• Chang S, Bray S, Li Z, et al. Identification of small molecules rescuing fragile X syndrome phenotypes in Drosophila. Nat Chem Biol. 2008;4:256–263.
   PubMed Web of Science ®Google Scholar
• Henderson C, Wijetunge L, Kinoshita M, et al. Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABAB receptors with arbaclofen. Sci Transl Med. 2012 Sep 19;4(152):152ra28.
   Web of Science ®Google Scholar
• Willoughby L, Schlosser T, Manning S, et al. An in vivo large-scale chemical screening platform using Drosophila for anti-cancer drug discovery. Dis Model Mech. 2013 Mar;6(2):521–529.
   PubMed Web of Science ®Google Scholar
• Gladstone M, Frederick B, Zheng D, et al. A translation inhibitor identified in a Drosophila screen enhances the effect of ionizing radiation and taxol in mammalian models of cancer. Dis Model Mech. 2012 May;5(3):342–350.
   PubMed Web of Science ®Google Scholar
• Salado I, Redondo M, Bello M, et al. Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis. J Med Chem. 2014;57(6):2755–2772.
   PubMed Web of Science ®Google Scholar
• Styczyńska-Soczka K, Zechini L, Zografos L. Validating the predicted effect of astemizole and ketoconazole using a Drosophila model of Parkinson’s Disease. Assay Drug Dev Technol. 2017;15(3):106–112.
   PubMed Web of Science ®Google Scholar
• Dar A, Das T, Shokat K, et al. Chemical genetic discovery of targets and anti-targets for cancer polypharmacology. Nature. 2012;486(7401):80–84.
   PubMed Web of Science ®Google Scholar
• Magen I, Davunetide: GI. Peptide therapeutic in neurological disorders. Curr Med Chem. 2014;21(23):2591–2598.
   PubMed Web of Science ®Google Scholar
• Vidal M, Wells S, Ryan A, et al. ZD6474 suppresses oncogenic RET isoforms in a Drosophila model for type 2 multiple endocrine neoplasia syndromes and papillary thyroid carcinoma. Cancer Res. 2005;65(9):3538–3541.
   PubMed Web of Science ®Google Scholar
• Sanz F, Solana-Manrique C, Muñoz-Soriano V, et al. Identification of potential therapeutic compounds for Parkinson’s disease using Drosophila and human cell models. Free Radic Biol Med. 2017 Jul;108:683–691.
   PubMed Web of Science ®Google Scholar
• Gouzi J, Moressis A, Walker J, et al. The receptor tyrosine kinase alk controls neurofibromin functions in Drosophila growth and learning. PLoS Genet. 2011;7(9):e1002281.
   PubMed Web of Science ®Google Scholar
• Weiss J, Weber S, Marzulla T, et al. Pharmacological inhibition of anaplastic lymphoma kinase rescues spatial memory impairments in neurofibromatosis 1 mutant mice. Behav Brain Res. 2017;332:337–342.
   PubMed Web of Science ®Google Scholar
• Gouzi J, Bouraimi M, Roussou I, et al. The Drosophila receptor tyrosine kinase alk constrains long-term memory formation. J Neurosci. 2018;38(35):7701–7712.
   PubMed Web of Science ®Google Scholar
• Markstein M, Dettorre S, Cho J, et al. Systematic screen of chemotherapeutics in Drosophila stem cell tumors.111(12):. Proc Natl Acad Sci U S A. 2014;111(12):4530–4535.
   PubMed Web of Science ®Google Scholar