ArticlePloS one2011
High-content chemical and RNAi screens for suppressors of neurotoxicity in a Huntington's disease model.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Identification of common genetic modifiers of neurodegenerative diseases from an integrative analysis of diverse genetic screens in model organisms.BMC genomics · 2012Pooled it
- Revealing the Mechanisms of Alzheimer's, Parkinson's and Huntington's Diseases Through Invertebrate Models.Biology · 2026Review
- Maternal antioxidant treatment partially rescues developmental defects in amicroPublication biology · 2025Article
- A Novel Huntington's Disease Assessment Platform to Support Future Drug Discovery and Development.International journal of molecular sciences · 2022Article
- Animal Models of Neurodegenerative Disease: Recent Advances in Fly Highlight Innovative Approaches to Drug Discovery.Frontiers in molecular neuroscience · 2022Review
- High-throughput synthetic rescue for exhaustive characterization of suppressor mutations in human genes.Cellular and molecular life sciences : CMLS · 2020Review
- High-throughput time-resolved morphology screening in bacteria reveals phenotypic responses to antibiotics.Communications biology · 2019Article
- Therapeutic strategies targeting connexins.Nature reviews. Drug discovery · 2018Review
- Deubiquitinase Usp12 functions noncatalytically to induce autophagy and confer neuroprotection in models of Huntington's disease.Nature communications · 2018Article
- Prion-Like Characteristics of Polyglutamine-Containing Proteins.Cold Spring Harbor perspectives in medicine · 2018Review
- Assay Development for High Content Quantification of Sod1 Mutant Protein Aggregate Formation in Living Cells.Journal of visualized experiments : JoVE · 2017Article
- High-content drug screening for rare diseases.Journal of inherited metabolic disease · 2017Review
- Pathogenic Huntington Alters BMP Signaling and Synaptic Growth through Local Disruptions of Endosomal Compartments.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- A Drosophila model of Huntington disease-like 2 exhibits nuclear toxicity and distinct pathogenic mechanisms from Huntington disease.Human molecular genetics · 2016Article
- iPSC-based drug screening for Huntington's disease.Brain research · 2016Review
- Compartmentalized Platforms for Neuro-Pharmacological Research.Current neuropharmacology · 2016Review
- Studying polyglutamine diseases in Drosophila.Experimental neurology · 2015Review
- Model organisms in the fight against muscular dystrophy: lessons from drosophila and Zebrafish.Molecules (Basel, Switzerland) · 2015Review
- Reinstating aberrant mTORC1 activity in Huntington's disease mice improves disease phenotypes.Neuron · 2015Article
- Decreased Phosphorylated Protein Kinase B (Akt) in Individuals with Autism Associated with High Epidermal Growth Factor Receptor (EGFR) and Low Gamma-Aminobutyric Acid (GABA).Biomarker insights · 2015Article
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5 authors.
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Abstract
To identify Huntington's Disease therapeutics, we conducted high-content small molecule and RNAi suppressor screens using a Drosophila primary neural culture Huntingtin model. Drosophila primary neurons offer a sensitive readout for neurotoxicty, as their neurites develop dysmorphic features in the presence of mutant polyglutamine-expanded Huntingtin compared to nonpathogenic Huntingtin. By tracking the subcellular distribution of mRFP-tagged pathogenic Huntingtin and assaying neurite branch morphology via live-imaging, we identified suppressors that could reduce Huntingtin aggregation and/or prevent the formation of dystrophic neurites. The custom algorithms we used to quantify neurite morphologies in complex cultures provide a useful tool for future high-content screening approaches focused on neurodegenerative disease models. Compounds previously found to be effective aggregation inhibitors in mammalian systems were also effective in Drosophila primary cultures, suggesting translational capacity between these models. However, we did not observe a direct correlation between the ability of a compound or gene knockdown to suppress aggregate formation and its ability to rescue dysmorphic neurites. Only a subset of aggregation inhibitors could revert dysmorphic cellular profiles. We identified lkb1, an upstream kinase in the mTOR/Insulin pathway, and four novel drugs, Camptothecin, OH-Camptothecin, 18β-Glycyrrhetinic acid, and Carbenoxolone, that were strong suppressors of mutant Huntingtin-induced neurotoxicity. Huntingtin neurotoxicity suppressors identified through our screen also restored viability in an in vivo Drosophila Huntington's Disease model, making them attractive candidates for further therapeutic evaluation.
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