Distinct roles for Toll and autophagy pathways in double-stranded RNA toxicity in a Drosophila model of expanded repeat neurodegenerative diseases.

ABSTRACT: Dominantly inherited expanded repeat neurodegenerative diseases are caused by the expansion of variable copy number tandem repeat sequences in otherwise unrelated genes. Some repeats encode polyglutamine that is thought to be toxic; however, other repeats do not encode polyglutamine indicating either multiple pathogenic pathways or an alternative common toxic agent. As these diseases share numerous clinical features and expanded repeat RNA is a common intermediary, RNA-based pathogenesis has been proposed, based on its toxicity in animal models. In Drosophila, double-stranded (rCAG.rCUG∼100) RNA toxicity is Dicer dependent and generates single-stranded (rCAG)7, an entity also detected in affected Huntington's Disease (HD) brains. We demonstrate that Drosophila rCAG.rCUG∼100 RNA toxicity pe

SUBMITTER: Samaraweera SE 

PROVIDER: S-EPMC3690966 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature