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.
|Number of pages||6|
|Publication status||Published - 27 Mar 2015|
Bibliographical noteCopyright © 2015, American Association for the Advancement of Science.
- Adaptor Proteins, Signal Transducing
- Aged, 80 and over
- Amyotrophic Lateral Sclerosis
- Genetic Association Studies
- Genetic Predisposition to Disease
- Middle Aged
- Protein Binding
- Protein-Serine-Threonine Kinases
- Sequence Analysis, DNA
- Transcription Factor TFIIIA
- Young Adult