Data di Pubblicazione:
2015
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.
Tipologia CRIS:
1.1 Articolo in rivista
Keywords:
Adaptor Proteins, Signal Transducing; Adolescent; Adult; Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Autophagy; Exome; Female; Genes; Genetic Association Studies; Humans; Male; Middle Aged; Protein Binding; Protein-Serine-Threonine Kinases; Risk; Sequence Analysis, DNA; Transcription Factor TFIIIA; Young Adult; Genetic Predisposition to Disease; Multidisciplinary
Elenco autori:
Cirulli, Et; Lasseigne, Bn; Petrovski, S; Sapp, Pc; Dion, Pa; Leblond, Cs; Couthouis, J; Lu, Yf; Wang, Q; Krueger, Bj; Ren, Z; Keebler, J; Han, Y; Levy, Se; Boone, Be; Wimbish, Jr; Waite, Ll; Jones, Al; Carulli, Jp; Day williams, Ag; Staropoli, Jf; Xin, Ww; Chesi, A; Raphael, Ar; Mckenna yasek, D; Cady, J; Vianney De Jong, Jm; Kenna, Kp; Smith, Bn; Topp, S; Miller, J; Gkazi, A; Fals Sequencing, Consortium; Al chalabi, A; Van Den Berg, Lh; Veldink, J; Silani, V; Ticozzi, N; Shaw, Ce; Baloh, Rh; Appel, S; Simpson, E; Lagier tourenne, C; Pulst, Sm; Gibson, S; Trojanowski, Jq; Elman, L; Mccluskey, L; Grossman, M; Shneider, Na; Chung, Wk; Ravits, Jm; Glass, Jd; Sims, Kb; Van Deerlin, Vm; Maniatis, T; Hayes, Sd; Ordureau, A; Swarup, S; Landers, J; Baas, F; Allen, As; Bedlack, Rs; Harper, Jw; Gitler, Ad; Rouleau, Ga; Brown, R; Harms, Mb; Cooper, Gm; Harris, T; Myers, Rm; Goldstein, Db; Sapp, Pc; Leblond, Cs; Mckenna yasek, D; Kenna, Kp; Smith, Bn; Topp, S; Miller, J; Gkazi, A; Al chalabi, A; Van Den Berg, Lh; Veldink, J; Silani, V; Ticozzi, N; Landers, J; Baas, F; Shaw, Ce; Glass, Jd; Rouleau, Ga; Brown, R; Hardiman, O; Mclaughlin, Rl; Mazzini, L; Blair, Ip; Williams, Kl; Nicholson, Ga; Al sarraj, S; King, A; Scotter, El; Topp, S; Troakes, C; Vance, C; D'Alfonso, S; Duga, S; Corrado, L; Ten Asbroek, Al; Calini, D; Colombrita, C; Ratti, A; Tiloca, C; Wu, Z; Asress, S; Polak, M; Diekstra, F; Nullw, nullVan Rheenen; Danielson, Ew; Fallini, C; Keagle, P; Lewis, Ea; Kost, J; Sorarù, G; Bertolin, C; Querin, G; Castellotti, B; Gellera, C; Pensato, V; Taroni, F; Cereda, Cristina; Gagliardi, S; Ceroni, Mauro; Lauria, G; Nullj, nullDe Belleroche; Comi, Gp; Corti, S; Nullr, nullDel Bo; Turner, Mr; Talbot, K; Pall, H; Morrison, Ke; Shaw, Pj; Esteban pérez, J; García redondo, A; Muñoz blanco, Jl
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