Drosophila models of amyotrophic lateral sclerosis with defects in RNA metabolism

• Published in: Brain research Vol. 1693; no. Pt A; pp. 109 - 120
• Main Authors: Zhang, Ke, Coyne, Alyssa N., Lloyd, Thomas E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.08.2018
• Subjects: Active Transport, Cell Nucleus; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - metabolism; Animals; C9orf72; Cytoplasmic Granules - genetics; Cytoplasmic Granules - metabolism; Disease Models, Animal; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Humans; Mutation; Nucleocytoplasmic transport; RNA - genetics; RNA - metabolism; Stress granule; Amyotrophic lateral sclerosis; Stress granule; Nucleocytoplasmic transport; Drosophila; C9orf72; RNA metabolism
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2018.04.043

•Drosophila Models of ALS are shedding new insight into pathogenesis of ALS.•Almost all aspects of RNA metabolism have been implicated in ALS.•Nucleocytoplasmic transport and stress granules are involved in pathogenesis of ALS caused by mutations in C9ORF72. The fruit fly Drosophila Melanogaster has been widely used to study neurodegenerative diseases. The conservation of nervous system biology coupled with the rapid life cycle and powerful genetic tools in the fly have enabled the identification of novel therapeutic targets that have been validated in vertebrate model systems and human patients. A recent example is in the study of the devastating motor neuron degenerative disease amyotrophic lateral sclerosis (ALS). Mutations in genes that regulate RNA metabolism are a major cause of inherited ALS, and functional analysis of these genes in the fly nervous system has shed light on how mutations cause disease. Importantly, unbiased genetic screens have identified key pathways that contribute to ALS pathogenesis such as nucleocytoplasmic transport and stress granule assembly. In this review, we will discuss the utilization of Drosophila models of ALS with defects in RNA metabolism.