Authors
Elizabeth T Cirulli, Brittany N Lasseigne, Slavé Petrovski, Peter C Sapp, Patrick A Dion, Claire S Leblond, Julien Couthouis, Yi-Fan Lu, Quanli Wang, Brian J Krueger, Zhong Ren, Jonathan Keebler, Yujun Han, Shawn E Levy, Braden E Boone, Jack R Wimbish, Lindsay L Waite, Angela L Jones, John P Carulli, Aaron G Day-Williams, John F Staropoli, Winnie W Xin, Alessandra Chesi, Alya R Raphael, Diane McKenna-Yasek, Janet Cady, JMB Vianney de Jong, Kevin P Kenna, Bradley N Smith, Simon Topp, Jack Miller, Athina Gkazi, FALS Sequencing Consortium, Ammar Al-Chalabi, Leonard H Van Den Berg, Jan Veldink, Vincenzo Silani, Nicola Ticozzi, Christopher E Shaw, Robert H Baloh, Stanley Appel, Ericka Simpson, Clotilde Lagier-Tourenne, Stefan M Pulst, Summer Gibson, John Q Trojanowski, Lauren Elman, Leo McCluskey, Murray Grossman, Neil A Shneider, Wendy K Chung, John M Ravits, Jonathan D Glass, Katherine B Sims, Vivianna M Van Deerlin, Tom Maniatis, Sebastian D Hayes, Alban Ordureau, Sharan Swarup, John Landers, Frank Baas, Andrew S Allen, Richard S Bedlack, J Wade Harper, Aaron D Gitler, Guy A Rouleau, Robert Brown, Matthew B Harms, Gregory M Cooper, Tim Harris, Richard M Myers, David B Goldstein
Publication date
2015/3/27
Journal
Science
Volume
347
Issue
6229
Pages
1436-1441
Publisher
American Association for the Advancement of Science
Description
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.
Scholar articles
ET Cirulli, BN Lasseigne, S Petrovski, PC Sapp… - Science, 2015