Aging causes distinct characteristics of polyglutamine amyloids in vivo

Ayako Tonoki, Erina Kuranaga, Natsuki Ito, Yoko Nekooki-Machida, Motomasa Tanaka, Masayuki Miura

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)557-564
Number of pages8
JournalGenes to Cells
Volume16
Issue number5
DOIs
Publication statusPublished - 2011 May
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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