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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
PubMed
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.

Keywords:
Alzheimer's diseaseBehaviorDrug DiscoveryHigh throughputNeurodegenerativeZebrafish larvae

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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.