Folding failure | Nature Reviews Neuroscience

Folding failure | Nature Reviews Neuroscience


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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


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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


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