Zebrafish in neurotoxin research: Insights into botulinum toxicity, mechanisms, and therapy

Botulinum neurotoxins (BoNTs) are highly potent biological toxins produced by Clostridium botulinum and related species. They act by inhibiting the release of acetylcholine at the neuromuscular junction, leading to paralysis. Due to their ability to modulate synaptic activity, BoNTs have been widely studied for their toxicological properties, as well as their medical and cosmetic applications, including the treatment of neuromuscular disorders, chronic pain, and aesthetic concerns. The zebrafish (Danio rerio) has gained prominence in BoNT research, particularly due to its genetic tractability and suitability for high-throughput screening, making it an effective model for studying BoNT effects at molecular, cellular, and behavioral levels. This review explores the role of zebrafish in neurotoxin research, highlighting its utility in studying BoNT toxicity, synaptic mechanisms, gene silencing applications, and therapeutic interventions. We discuss zebrafish-based studies that provide insights into BoNT-induced behavioral and cognitive effects. Additionally, we examine how zebrafish facilitate high-throughput screening for BoNT-related compounds and antitoxins. Despite the contributions of zebrafish-based models in neurotoxicology, further research is needed to fully elucidate BoNT mechanisms and optimize a putative therapeutic potential.