부산대학교 도서관

• The use of Caenorhabditis elegans , Drosophila melanogaster and Danio rerio as alternative animal models in ALS studies. • Overview of genetic models for C9ORF72 , SOD1 , TARDBP , FUS and other less common ALS-associated genes. • Screening platforms in small animal models contributed to new insights in ALS disease mechanisms and therapeutic strategies. • Fruit flies, zebrafish or worms as alternatives or prerequisites for rodent models in preclinical ALS studies? Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder characterized by the loss of upper and lower motor neurons. In general, patients succumb to respiratory insufficiency due to respiratory muscle weakness. Despite many promising therapeutic strategies primarily identified in rodent models, patient trials remain rather unsuccessful. There is a clear need for alternative approaches, which could provide directions towards the justified use of rodents and which increase the likelihood to identify new promising clinical candidates. In the last decades, the use of fast genetic approaches and the development of high-throughput screening platforms in the nematode Caenorhabditis elegans , in the fruit fly (Drosophila melanogaster) and in zebrafish (Danio rerio) have contributed to new insights into ALS pathomechanisms, disease modifiers and therapeutic targets. In this mini-review, we provide an overview of these alternative small animal studies, modeling the most common ALS genes and discuss the most recent preclinical discoveries. We conclude that small animal models will not replace rodent models, yet they clearly represent an important asset for preclinical studies. [ABSTRACT FROM AUTHOR]