RNA pathogenesis via Toll-like receptor-activated inflammation in expanded repeat neurodegenerative diseases.

ABSTRACT: Previously, we hypothesized that an RNA-based pathogenic pathway has a causal role in the dominantly inherited unstable expanded repeat neurodegenerative diseases. In support of this hypothesis we, and others, have characterized rCAG.rCUG 100 repeat double-strand RNA (dsRNA) as a previously unidentified agent capable of causing pathogenesis in a Drosophila model of neurodegenerative disease. Dicer, Toll, and autophagy pathways have distinct roles in this Drosophila dsRNA pathology. Dicer dependence is accompanied by cleavage of rCAG.rCUG 100 repeat dsRNA down to r(CAG) 7 21-mers. Among the "molecular hallmarks" of this pathway that have been identified in Drosophila, some [i.e., r(CAG) 7 and elevated tumor necrosis factor] correlate with observations in affected people (e.g., Huntington's

SUBMITTER: Richards RI 

PROVIDER: S-EPMC3763583 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature