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Updated: Sep 13, 2025

Caenorhabditis elegans as a Model System for Discovering Bioactive Compounds Against Polyglutamine-Mediated Neurotoxicity
Published on: September 21, 2021
C. elegans as a powerful model for neurotoxicity assessment.
Daniel José Barbosa1, Inês C Santos2, Tatiana Moyisyeyenko1
1Associate Laboratory i4HB - Institute for Health and Bioeconomy, University Institute of Health Sciences - CESPU, 4585-116 Gandra, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal.
The nematode Caenorhabditis elegans (C. elegans) is a powerful model for neurotoxicology research, offering insights into how substances like pesticides and microplastics affect the nervous system. Its genetic and molecular pathways are highly conserved with humans, aiding in toxicity screening.
Area of Science:
- Neurotoxicology and Model Organism Research
- Genetics and Molecular Biology
- Environmental Health Science
Background:
- Caenorhabditis elegans (C. elegans) possesses a well-characterized nervous system and genetic tractability, making it ideal for studying neurotoxicity.
- Conserved molecular pathways between C. elegans and humans facilitate the investigation of cellular and molecular mechanisms underlying neurotoxic effects.
- The nematode model is crucial for understanding neurotoxicant impacts, from classical agents to emerging contaminants like microplastics.
Purpose of the Study:
- To provide an updated review of C. elegans as a model organism in neurotoxicology.
- To detail diverse neurotoxicity assays and genetic models applicable in C. elegans research.
- To explore the relevance of C. elegans in regulatory frameworks, including adverse outcome pathways (AOPs).
Main Methods:
- Utilizing behavioral, molecular, neurophysiological, and neuronal morphology assays in C. elegans.
- Employing genetic models for neurotransmitter signaling, mitochondrial dysfunction, and oxidative stress.
- Reviewing classical and emerging neurotoxicants, including heavy metals, pesticides, microplastics, industrial chemicals, and pharmaceuticals.
Main Results:
- C. elegans enables high-throughput neurotoxicity screening with enhanced scalability and accuracy through automated systems.
- The model is effective for elucidating mechanisms of neurotoxicity across various substance classes.
- Despite limitations like the absence of a blood-brain barrier, C. elegans remains a robust tool for neurotoxic screening and mechanistic studies.
Conclusions:
- C. elegans is a versatile and valuable model for neurotoxicology, bridging mechanistic studies with regulatory science.
- The review highlights the utility of C. elegans in assessing a broad spectrum of neurotoxicants and their impact on nervous system function.
- Integrating C. elegans research into frameworks like AOPs enhances its translational value for human health risk assessment.

