| Literature DB >> 25700176 |
Elizabeth T Cirulli1, Brittany N Lasseigne2, Slavé Petrovski3, Peter C Sapp4, Patrick A Dion5, Claire S Leblond5, Julien Couthouis6, Yi-Fan Lu3, Quanli Wang3, Brian J Krueger3, Zhong Ren3, Jonathan Keebler7, Yujun Han7, Shawn E Levy2, Braden E Boone2, Jack R Wimbish2, Lindsay L Waite2, Angela L Jones2, John P Carulli8, Aaron G Day-Williams8, John F Staropoli8, Winnie W Xin9, Alessandra Chesi6, Alya R Raphael6, Diane McKenna-Yasek4, Janet Cady10, J M B Vianney de Jong11, Kevin P Kenna12, Bradley N Smith13, Simon Topp13, Jack Miller13, Athina Gkazi13, Ammar Al-Chalabi13, Leonard H van den Berg14, Jan Veldink14, Vincenzo Silani15, Nicola Ticozzi15, Christopher E Shaw13, Robert H Baloh16, Stanley Appel17, Ericka Simpson17, Clotilde Lagier-Tourenne18, Stefan M Pulst19, Summer Gibson19, John Q Trojanowski20, Lauren Elman21, Leo McCluskey21, Murray Grossman22, Neil A Shneider23, Wendy K Chung24, John M Ravits25, Jonathan D Glass26, Katherine B Sims9, Vivianna M Van Deerlin20, Tom Maniatis27, Sebastian D Hayes28, Alban Ordureau29, Sharan Swarup29, John Landers4, Frank Baas11, Andrew S Allen30, Richard S Bedlack31, J Wade Harper29, Aaron D Gitler6, Guy A Rouleau5, Robert Brown4, Matthew B Harms10, Gregory M Cooper2, Tim Harris32, Richard M Myers2, David B Goldstein3.
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.Entities:
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Year: 2015 PMID： 25700176 PMCID： PMC4437632 DOI： 10.1126/science.aaa3650
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728