Drosophila models of amyotrophic lateral sclerosis with defects in RNA metabolism

Brain Res. 2018 Aug 15;1693(Pt A):109-120. doi: 10.1016/j.brainres.2018.04.043. Epub 2018 May 9.

Abstract

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.

Keywords: Amyotrophic lateral sclerosis; C9orf72; Drosophila; Nucleocytoplasmic transport; RNA metabolism; Stress granule.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Active Transport, Cell Nucleus
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Animals
  • Cytoplasmic Granules / genetics
  • Cytoplasmic Granules / metabolism
  • Disease Models, Animal
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Humans
  • Mutation
  • RNA / genetics
  • RNA / metabolism*

Substances

  • Drosophila Proteins
  • RNA