Zebrafish as an Alternative Animal Model of Huntington’s Disease: Challenges and Future Directions

Huntington’s disease (HD) is a lethal autosomal dominant neurodegenerative disorder characterized by progressing cognitive, motor, and other behavioral deficits. Animal models, especially rodent-based, are a valuable tool to study brain disorders, including HD. Given the existence of multiple valid and predictive models of HD and other brain disorders, we are now entering a phase of mechanistic discovery, as research shifts towards phenotype-based screening and multi-omic validation. In addition to rodent models, zebrafish (Danio rerio) are rapidly becoming a promising model organism for translational HD research. With considerable genetic homology to humans, embryonic transparency for real-time pathology tracking, physiological similarity to mammals, and high-throughput drug screening potential, zebrafish have become a valuable alternative model organism in translational HD research. Here, we discuss zebrafish HD models, their advantages and limitations, and future directions of translational research in this field.