Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways Academic Article uri icon

Overview

MeSH Major

  • Amyotrophic Lateral Sclerosis
  • Autophagy
  • Exome
  • Genetic Predisposition to Disease
  • Protein-Serine-Threonine Kinases

abstract

  • Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of a moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS. We performed whole-exome sequencing of 2869 ALS patients and 6405 controls. Several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS. These observations reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention.

authors

publication date

  • March 27, 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4437632

Digital Object Identifier (DOI)

  • 10.1126/science.aaa3650

PubMed ID

  • 25700176

Additional Document Info

start page

  • 1436

end page

  • 41

volume

  • 347

number

  • 6229