Drosophila in the Study of Neurodegenerative Disease

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Drosophila in the Study of Neurodegenerative Disease J. Lawrence Marsh, Leslie Michels Thompson Neuron Volume 52, Issue 1, Pages 169-178 (October 2006) DOI: 10.1016/j.neuron.2006.09.025 Copyright © 2006 Elsevier Inc. Terms and Conditions

Figure 1 Humanized Flies Express Human Genes in Drosophila with the Binary GAL4/UAS System Genes can be either mutant disease genes or modifiers of human disease genes. Neuron 2006 52, 169-178DOI: (10.1016/j.neuron.2006.09.025) Copyright © 2006 Elsevier Inc. Terms and Conditions

Figure 2 Schematic of Utility of Drosophila Models of Neurodegenerative Disease Neuron 2006 52, 169-178DOI: (10.1016/j.neuron.2006.09.025) Copyright © 2006 Elsevier Inc. Terms and Conditions

Figure 3 EGCG Diminishes the Toxicity of Mutant htt Fragments in Fly Models of HD (A) Rescue of degeneration of photoreceptor neurons in Drosophila expressing mutant htt fragments with 93 glutamines. Newly eclosed flies were kept on food supplemented with different amounts of EGCG (0.01, 0.1, 1, 10, and 100 μM) or solvent only, and the average number of photoreceptor cells per ommatidium were scored 7 days post-eclosion via the pseudopupil technique. Error bars represent ± standard error. Day 0 shows the neuronal loss that has occurred during pupal development prior to drug treatment. Values for ≥0.1 μM are all significantly different (p < 0.002) from the no-drug control; 0.01 μM EGCG had no significant effect. Maximal rescue in the representative experiment shown was 29%. (B) Representative deep-pseudopupil images of eyes from 7-day-old EGCG-treated and solvent-treated flies. Left panel: Solvent-treated flies show extensive degeneration with many ommatidia containing either three (white arrowhead) or four (yellow arrowhead) rhabdomeres. Right panel: Flies fed 100 μM EGCG show less degeneration; most ommatidia contain 5–6 rhabdomeres, with some retaining seven (green arrowhead). (C) Age-dependent deterioration of climbing abilities in flies expressing mutant htt fragments with 93 glutamines (UAS-httQ93) in neurons was monitored by placement of the flies on the bottom of a vertical glass tube and measurement of the distance covered within 60 s. Flies mated and raised on food with 500 μM EGCG performed significantly better than solvent-treated controls. From Ehrnhoefer et al. [2006], by permission of Oxford University Press. Neuron 2006 52, 169-178DOI: (10.1016/j.neuron.2006.09.025) Copyright © 2006 Elsevier Inc. Terms and Conditions