Tonoki, A., Kuranaga, E., Ito, N., Nekooki-Machida, Y., Tanaka, M., Miura, M. (2011). Aging causes distinct characteristics of polyglutamine amyloids in vivo.  Genes Cells 16(5): 557--564.

FBrf0213535

Research paper

Polyglutamine diseases, including Machado-Joseph disease and Huntington's disease, typically appear in midlife and are characterized by amyloid accumulations of abnormally expanded polyglutamine proteins. Although there is growing evidence that aging has an important role in the occurrence of such diseases, the role of aging in the late onset of these diseases is not well understood. Recent studies showed that differences in amyloid conformation from different brain regions lead to differing toxicity. We hypothesized that higher amyloid toxicity at later ages might cause the late onset of polyglutamine diseases. Using a method for temporal and regional gene expression targeting (TARGET) in Drosophila, we showed that transient polyglutamine expression caused more severe neurodegeneration in older flies than in younger flies. Moreover, the polyglutamine amyloids themselves showed distinct characteristics in relation to age; those from older flies were less resistant to SDS and more effective at seeding polymerization than those from younger flies, suggesting that the polyglutamine amyloids in aged individuals may have higher toxicity. These findings show that age-related changes in amyloid characteristics may be a trigger for late-onset polyglutamine diseases.