Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways.
Science
; 347(6229): 1436-41, 2015 Mar 27.
Article
em En
| MEDLINE
| ID: mdl-25700176
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Proteínas Serina-Treonina Quinases
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Predisposição Genética para Doença
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Exoma
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Esclerose Lateral Amiotrófica
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article