RNA-Binding Proteins in Amyotrophic Lateral Sclerosis

Mol Cells. 2018 Sep 30;41(9):818-829. doi: 10.14348/molcells.2018.0243. Epub 2018 Aug 29.

Abstract

Significant research efforts are ongoing to elucidate the complex molecular mechanisms underlying amyotrophic lateral sclerosis (ALS), which may in turn pinpoint potential therapeutic targets for treatment. The ALS research field has evolved with recent discoveries of numerous genetic mutations in ALS patients, many of which are in genes encoding RNA binding proteins (RBPs), including TDP-43, FUS, ATXN2, TAF15, EWSR1, hnRNPA1, hnRNPA2/B1, MATR3 and TIA1. Accumulating evidence from studies on these ALS-linked RBPs suggests that dysregulation of RNA metabolism, cytoplasmic mislocalization of RBPs, dysfunction in stress granule dynamics of RBPs and increased propensity of mutant RBPs to aggregate may lead to ALS pathogenesis. Here, we review current knowledge of the biological function of these RBPs and the contributions of ALS-linked mutations to disease pathogenesis.

Keywords: ALS; RNA-binding proteins.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • Animals, Genetically Modified
  • Cytoplasmic Granules / metabolism
  • Humans
  • Models, Animal
  • Mutation
  • Neurons / metabolism
  • RNA / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism*

Substances

  • RNA-Binding Proteins
  • RNA