Table 2.
D. melanogaster models of ND used for small molecule screening.
| Drosophila model | Dev. stage | Screen design | Output measurement | References |
|---|---|---|---|---|
| A53T/A30P α-synuclein mutants (PD) | Adult | Candidate drug Decalepis Hamiltonii extract (known antioxidant) was fed to the flies for 21 Days. |
Negative Geotaxis Assay PQ Toxicity assay Lifespan assay |
Jahromi et al., 2015 |
| Lrrk2 mutants (PD) | Adult | Piceatannol, Thymoquinone, and Esculetin mixed with DMSO was incorporated into the fly food and fed to mutants. | Oxidative state assays Climbing assays Immunostaining Western blots |
Angeles et al., 2016 |
| PINK1 mutants (PD) | Larval | High-throughput screening of a compound library identified 2 small molecules (T0466 and T0467) which were effective. | Immunostaining Western Blots |
Shiba-Fukushima et al., 2020 |
| PINK1 mutants (PD) | Larval | High-throughput screening of 320 compounds which found 3 effective compounds (MRS1220, tranylcypromine, bromocriptine). | Immunostaining Crawling assays |
Yamaguchi et al., 2020 |
| DJ-1 double knockout mutants (PD) | Adult | Exposed mutants to a variety of oxidative stressors (paraquat), proteasome blockers (MG132), and agents that unfold proteins (dithiothreitol). | Lifespan assay Western blots |
Meulener et al., 2005 |
| DJ-1 mutants (PD) | Adult | Screened a variety of human used drugs for PD and other experimental drugs at highest possible concentration. All drugs were fed to flies. | Climbing assay Peroxide measurement Carbonyl formation assessment |
Sanz et al., 2017 |
| Expression of human N370S GBA (PD) | Adult | The compound Nicotinamide Riboside was identified for study, and mixed with adult mutant fly food. | Anti -TH staining Climbing assay Dopaminergic Neuron counting |
Schöndorf et al., 2018 |
| Aβ42 mutants (AD) | Adult | Extracts from brown alga and prickly pear plants were fed to flies. | Lifespan assay Climbing assay Western blots Liposome assay |
Briffa et al., 2017 |
| Aβ42 mutants (AD) | Adult | Extracts from multiple plants were used in a high throughput screen with adult flies. | Protein quantitation Memory tests |
Ma et al., 2017 |
| Expression of human APP and BACE1 (AD) | Adult | Flies were fed food mixed with γ-secretase transition state inhibitor L-685,458 throughout their entire lifespan | Lifespan assay Climbing assay Immunostaining for amyloid deposition Courtship Behavior Assay |
Chakraborty et al., 2011 |
| Expression of mutations in human tau transgene (tauR406W) (AD) | Adult | Biotin was identified as a potential therapeutic and therefore flies were fed various diets containing various levels of biotin. | Locomotor assay Enzyme linked immunosorbent assay Western blotting |
Lohr et al., 2020 |
| Expression of mutations in human tau transgene (tauR406W and tauP301L) (AD) | Adult | A screen of compounds was conducted that identified Ro 31-8220 as a potential effective treatment. The compound was then mixed with standard fly food. | Lifespan assay Negative geotaxis assay Learning and memory assay |
Shim et al., 2019 |
| SOD1 mutants (ALS) | Adult | α-Lipoic acid mixture was mixed into the food and fed to the mutant flies. | Behavior assay Enzyme activity assay Lifespan assay |
Wang et al., 2018 |
| Wild Type TDP 43 mutants (ALS) | Larval | A virtual and physical screen of compounds was performed to select for compatible TDP-43 targets. The compatible compounds were then fed to larvae. | Larval turning assay | François-Moutal et al., 2019 |
| Expression of Human Htt at various Poly-Q lengths including Q15 and Q138 (HD) | Cell culture Adult | Screen of a compound library that produced multiple novel drug hits. | Negative geotaxis assay Confocal microscopy |
Schulte et al., 2011 |
| Expression of human mutant Htt Exon One (Q93) (HD) | Adult | Screened small molecule library for effectiveness in reducing HD phenotype. Drugs were delivered via mixture with food. | Neurodegeneration assay | Desai et al., 2006 |
| Expression of human mutant Htt Exon One (Q93) (HD) | Adult | Connectivity mapping revealed potential therapeutic genes and chemicals. These identified chemicals were then mixed with food and introduced to the mutants. | Pseudopupil assay | Smalley et al., 2016 |
| Expression of human mutant Htt (Q93) (HD) | Adult Larval | The drug resveratrol was identified to attempt to inhibit Sir2 and Rpd3 genes which play important roles in HDAC activity. Drugs were delivered via a mixture of fly food. | Lifespan assay Neuronal survival frequency |
Pallos et al., 2008 |
| Expression of human mutant Htt (Q93) (HD) | Adult | High-throughput screening combined with a FRET assay identified one lead therapeutic compound Y-27632 which was fed to flies. | Rhabdomeres assay | Pollitt et al., 2003 |
| Expression of full length Htt with 16Q and 128Q (HD) | Adult | High-throughput screening identified compounds of interest for study. These were then fed to flies in a mixture of fly food. | Western Blot Filter trap assay HTRF assay c-Raf kinase assay Pull-down assay Autophagy assay Behavioral assay Lifespan assay |
Li Z. et al., 2019 |