ArticleMolecular neurodegeneration2016
ZNStress: a high-throughput drug screening protocol for identification of compounds modulating neuronal stress in the transgenic mutant sod1G93R zebrafish model of amyotrophic lateral sclerosis.
Article in Molecular neurodegeneration, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 40 citations in OpenAlex.
- Review
- Human TDP-43 overexpression in zebrafish motor neurons triggers MND-like phenotypes through gain-of-function mechanism.Acta neuropathologica communications · 2025Article
- Anxiolytic and Antidepressant Effects ofPharmaceuticals (Basel, Switzerland) · 2024Article
- C9ORF72 Deficiency Results in Neurodegeneration in the Zebrafish Retina.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Assessing Drug Administration Techniques in Zebrafish Models of Neurological Disease.International journal of molecular sciences · 2023Review
- A multilevel screening pipeline in zebrafish identifies therapeutic drugs for GAN.EMBO molecular medicine · 2023Article
- Zebrafish Is a Powerful Tool for Precision Medicine Approaches to Neurological Disorders.Frontiers in molecular neuroscience · 2022Review
- Zebrafish and Medaka: Important Animal Models for Human Neurodegenerative Diseases.International journal of molecular sciences · 2021Review
- Automated in vivo drug screen in zebrafish identifies synapse-stabilising drugs with relevance to spinal muscular atrophy.Disease models & mechanisms · 2021Article
- High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases.Bioengineering (Basel, Switzerland) · 2021Review
- Advances of Zebrafish in Neurodegenerative Disease: From Models to Drug Discovery.Frontiers in pharmacology · 2021Review
- ModellingBiomedicines · 2020Review
- Efficacy of Ciprofloxacin/Celecoxib combination in zebrafish models of amyotrophic lateral sclerosis.Annals of clinical and translational neurology · 2020Article
- Motor Neuron Abnormalities Correlate with Impaired Movement in Zebrafish that Express Mutant Superoxide Dismutase 1.Zebrafish · 2019Article
- Application of the Transcriptional Disease Signature (TDSs) to Screen Melanoma-Effective Compounds in a Small Fish Model.Scientific reports · 2019Article
- Stable transgenic C9orf72 zebrafish model key aspects of the ALS/FTD phenotype and reveal novel pathological features.Acta neuropathologica communications · 2018Article
- Modulation of the zebrafish optokinetic reflex by pharmacologic agents targeting GABANeuroscience letters · 2018Article
- An open-source method to analyze optokinetic reflex responses in larval zebrafish.Journal of neuroscience methods · 2018Article
- A High-Content Larval Zebrafish Brain Imaging Method for Small Molecule Drug Discovery.PloS one · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAmyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease with death on average within 2-3 years of symptom onset. Mutations in superoxide dismutase 1 (SOD1) have been identified to cause ALS. Riluzole, the only neuroprotective drug for ALS provides life extension of only 3 months on average. Thishighlights the need for compound screening in disease models to identify new neuroprotective therapies for this disease. Zebrafish is an emerging model system that is well suited for the study of diseasepathophysiology and also for high throughput (HT) drug screening. The mutant sod1 zebrafish model of ALS mimics the hallmark features of ALS. Using a fluorescence based readout of neuronal stress, we developed a high throughput (HT) screen to identify neuroprotective compounds.
resultsHere we show that the zebrafish screen is a robust system that can be used to rapidly screen thousands ofcompounds and also demonstrate that riluzole is capable of reducing neuronal stress in this model system. The screen shows optimal quality control, maintaining a high sensitivity and specificity withoutcompromising throughput. Most importantly, we demonstrate that many compounds previously failed in human clinical trials, showed no stress reducing activity in the zebrafish assay.
conclusionWe conclude that HT drug screening using a mutant sod1 zebrafish is a reliable model system which supplemented with secondary assays would be useful in identifying drugs with potential for neuroprotective efficacy in ALS.
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