The Stress of Misfolded Proteins

C. elegans Models for Neurodegenerative Disease and Aging
  • Heather R. Brignull
  • James F. Morley
  • Richard I. MorimotoEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 594)


A growing number of human neurodegenerative diseases are associated with the expres-ion of misfolded proteins that oligomerize and form aggregate structures. Over time, accumulation of misfolded proteins leads to the disruption of cellular protein folding homeostasis and eventually to cellular dysfunction and death. To investigate the relationship between misfolded proteins, neuropathology and aging, we have developed models utilizing the nematode C. elegans. In addition to being genetically tractable, C. elegans have rapid growth rates and short life-cycles, providing unique advantages for modeling neurodegenerative diseases of aging caused by the stress of misfolded proteins. The C. elegans models described here express polyglutamine expansion-containing proteins, as occur in Huntington’s disease. Through the use of tissue-specific expression of different lengths of fluorescently tagged polyglutamine repeats, we have examined the dynamics of aggregate formation both within individual cells and over time throughout the lifetime of individual animals, identifying aging and other genetic modifiers as an important physiologic determinant of aggregation and toxicity.


Fluorescence Resonance Energy Transfer Misfolded Protein Fluorescence Recovery After Photobleaching Permissive Temperature polyQ Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Heather R. Brignull
    • 1
  • James F. Morley
    • 1
  • Richard I. Morimoto
    • 1
    Email author
  1. 1.Department of Biochemistry, Molecular Biology, and Cell Biology. Rice Institute for Biomedical ResearchNorthwestern UniversityEvanstonUSA

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