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Updated: Jul 30, 2026
10:01
Modeling Amyloid-β42 Toxicity and Neurodegeneration in Adult Zebrafish Brain
Published on: October 25, 2017
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Drug repurposing for neurodegenerative diseases using Zebrafish behavioral profiles
Thaís Del Rosario Hernández1, Sayali V Gore1, Jill A Kreiling1
1Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.
Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|January 7, 2024
Summary
This study repurposed FDA-approved drugs for Alzheimer's disease (AD) using a zebrafish larvae behavioral model. Researchers identified 64 potential therapeutics for neurodegenerative disorders by screening compounds for calcineurin inhibitor-like effects.
Area of Science:
- Neuroscience
- Pharmacology
- Computational Biology
Background:
- Drug repurposing offers a cost-effective strategy for developing therapeutics for neurodegenerative diseases like Alzheimer's disease (AD).
- Existing treatments for AD are limited, highlighting the need for novel therapeutic approaches.
- Zebrafish larvae models provide a valuable platform for high-throughput screening of drug candidates.
Purpose of the Study:
- To identify FDA-approved drugs that can be repurposed for treating neurodegenerative disorders, specifically Alzheimer's disease.
- To utilize a novel neural network model (Z-LaP Tracker) for high-throughput behavioral screening in zebrafish larvae.
- To discover compounds exhibiting behavioral profiles similar to calcineurin inhibitors, which are of interest for AD prevention.
Main Methods:
- Development and application of the Z-LaP Tracker neural network model to quantify zebrafish larval behaviors (activity, reactivity, swimming patterns, optomotor response).
- High-throughput screening of a library of FDA-approved drugs using the Z-LaP Tracker model.
- Generation of behavioral profiles for cluster analysis to identify candidate therapeutics.
Main Results:
- The Z-LaP Tracker model successfully quantified complex behaviors in zebrafish larvae.
- High-throughput screening identified compounds that modulated zebrafish larval behavior in a manner consistent with calcineurin inhibitors.
- Cluster analysis of behavioral profiles led to the identification of 64 candidate therapeutics for neurodegenerative disorders.
Conclusions:
- Drug repurposing using advanced behavioral analysis in zebrafish larvae is a viable strategy for discovering novel therapeutics for neurodegenerative diseases.
- The identified 64 candidate drugs warrant further investigation for their potential in treating conditions like Alzheimer's disease.
- This approach accelerates the identification of potential treatments, reducing the time and cost associated with traditional drug development.
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