Folding failure | Nature Reviews Neuroscience

Access through your institution Buy or subscribe Proteins with expanded glutamine repeats (polyQ) are associated with several fatal neurodegenerative diseases, including Huntington's

disease. The polyQ expansion leads to the protein becoming abnormally folded, prone to aggregation and, consequently, cytotoxic. A report in _Science_ reveals that polyQ aggregates exert

their cytotoxic effect by disrupting the carefully balanced cellular homeostasis of protein folding and clearance. Temperature-sensitive mutant proteins provide a useful genetic model of

such metastable variants. At permissive temperatures they convey no abnormal phenotype, but at raised, restrictive temperatures the metastable balance is tilted, and the proteins misfold and

fail to function. The group used various temperature-sensitive _Caenorhabditis elegans_ strains and crossed them with transgenic lines expressing polyQ proteins. Normally,

temperature-sensitive strains show their defective phenotype only at restrictive temperatures. However, when crossed with the polyQ worms the defective phenotype became apparent even at

permissive temperatures. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print

issues and online access $189.00 per year only $15.75 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to

local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support ORIGINAL RESEARCH

PAPER * Gidalevitz, T. et al. Progressive disruption of cellular protein folding in models of polyglutamine diseases. _Science_ 9 Feb 2006 (doi:10.1126/science.1124514) Download references

Authors * Ruth Williams View author publications You can also search for this author inPubMed Google Scholar RELATED LINKS RELATED LINKS WEB SITE Morimoto's laboratory RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Williams, R. Folding failure. _Nat Rev Neurosci_ 7, 252 (2006). https://doi.org/10.1038/nrn1890 Download citation *

Published: 16 March 2006 * Issue Date: 01 April 2006 * DOI: https://doi.org/10.1038/nrn1890 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get

shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative