Swimming against ALS: How to model disease in zebrafish for pathophysiological and behavioral studies

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that leads to progressive disability and motor impairment. Existing therapies provide modest improvements in patient survival, raising a need for new treat-ments for ALS. Zebrafish is a promising model animal for translational and fundamental research in ALS - it is an experimentally tractable vertebrate, with high homology to humans and an ample experimental toolbox. These advantages allow high-throughput study of behavioral and pathophysiological phenotypes. The last decade saw an increased interest in modelling ALS in zebrafish, leading to the current abundance and variety of available methods and models. Additionally, the rise of gene editing techniques and toxin combination studies has created novel opportunities for ALS studies in zebrafish. In this review, we address the relevance of zebrafish as a model animal for ALS studies, the strategies for model induction and key phenotypical evaluation. Furthermore, we discuss established and emerging zebrafish models of ALS, analyzing their validity, including their potential for drug testing, and highlighting research opportunities in this area.

Automated summary

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that causes disability and motor impairment. Zebrafish has emerged as a promising model for studying ALS due to its similarities to humans and the ability to study behavioral and pathophysiological phenotypes. This review discusses the relevance of zebrafish in ALS studies, model induction strategies, and various zebrafish models of ALS, highlighting their validity and potential for drug testing.