Zebrafish Models of Rare Neurological Diseases like Spinocerebellar Ataxias (SCAs): Advantages and Limitations

SIMPLE SUMMARY: Zebrafish can be used as an effective model for studying various genetic neurological disorders, such as spinocerebellar ataxias. They are cost effective, easy to genetically manipulate, transparent in the larvae stage allowing for in vivo imaging, and amenable to rapid compound screens. Zebrafish can link the gap between neuro-specific drug discovery and clinical trials. ABSTRACT: Spinocerebellar ataxia (SCA) is a heterogeneous group of rare familial neurodegenerative disorders that share the key feature of cerebellar ataxia. Clinical heterogeneity, diverse gene mutations and complex neuropathology pose significant challenges for developing effective disease-modifying therapies in SCAs. Without a deep understanding of the molecular mechanisms involved for each SCA, we cannot succeed in developing targeted therapies. Animal models are our best tool to address these issues and several have been generated to study the pathological conditions of SCAs. Among them, zebrafish (Danio rerio) models are emerging as a powerful tool for in vivo study of SCAs, as well as rapid drug screens. In this review, we will summarize recent progress in using zebrafish to study the pathology of SCAs. We will discuss recent advancements on how zebrafish models can further clarify underlying genetic, neuroanatomical, and behavioral pathogenic mechanisms of disease. We highlight their usefulness in rapid drug discovery and large screens. Finally, we will discuss the advantages and limitations of this in vivo model to develop tailored therapeutic strategies for SCA.