Cell-to-cell Transmission of Polyglutamine Aggregates inC. elegans

• DOI: 10.5607/en.2017.26.6.321
• Publication Date: 2017-12-27T07:58:56Z
• Authors: Dong-Kyu Kim; Kyu-Won Cho; Woo Jung Ahn; Dayana Acuña; Hyunsu Jeong; He-Jin Lee; Seung-Jae Lee
• Keywords: 0301 basic medicine; 03 medical and health sciences; Original Article

Huntington disease (HD) is an inherited neurodegenerative disorder characterized by motor and cognitive dysfunction caused expansion of polyglutamine (polyQ) repeat in exon 1 huntingtin (HTT).In patients, the number glutamine residues polyQ tracts are over 35, it correlated with age onset, severity, progression.Expansion increases propensity for HTT protein aggregation, process known to be implicated neurodegeneration.These pathological aggregates can transmitted from neuron another neuron, this may explain spreading aggregates.Here, we developed vivo model studying transmission a highly quantitative manner real time.HTT expanded was fused either N-terminal or C-terminal fragments Venus fluorescence expressed pharyngeal muscles associated neurons, respectively, C. elegans.Transmission proteins detected using bimolecular complementation (BiFC).Mutant (Q97) much more efficiently than wild type (Q25) forms numerous inclusion bodies as well.The Q97 gradually increased aging animal.The animals exhibited degenerative phenotypes, such nerve degeneration, impaired pumping behavior, reduced life span.The elegans presented here would useful system study aggregate propagation might applied screening genetic chemical modifiers propagation.