The stress of misfolded proteins: C. elegans models for neurodegenerative disease and aging

Heather R. Brignull, James F. Morley, Richard I. Morimoto

Research output: Chapter in Book/Report/Conference proceedingChapter

52 Scopus citations

Abstract

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.

Original languageEnglish (US)
Title of host publicationMolecular Aspects of the Stress Response
Subtitle of host publicationChaperones, Membranes and Networks
PublisherSpringer New York
Pages167-189
Number of pages23
ISBN (Print)9780387399744
DOIs
StatePublished - Jan 1 2007

Publication series

NameAdvances in Experimental Medicine and Biology
Volume594
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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