Linked Life Data

17560603

Source:http://linkedlifedata.com/resource/pubmed/id/17560603

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-7-13
pubmed:abstractText
Abnormally expanded polyglutamine (polyQ) tracts provide a gain of toxic functions to nine otherwise unrelated human proteins and induce progressive neurodegenerative diseases. Over the past ten years, it was suggested that only polyQ tracts longer than a specific threshold adopt a particular structure, which would be the cause of the apparent polyQ length-dependent toxicity threshold observed in polyQ diseases. We have used a combination of biochemical and biophysical approaches to compare the structural properties of polyQ of pathogenic and non-pathogenic lengths under various conditions. We observe that pathogenic and non-pathogenic polyQ, as soluble species and upon interaction with a partner, during aggregation, or as mature aggregates, display very similar structural properties. PolyQ length only influences the aggregation kinetics and, to a lesser extent, the stability of the aggregates. We thus propose that polyQ toxicity does not depend on a structural transition occurring above a specific threshold, but rather that polyQ tracts are inherently toxic sequences, whose deleterious effect gradually increases with their length. We discuss how polyQ properties and other cellular factors may explain the existence of an apparent polyQ length-dependent toxicity threshold.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
371
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
235-44
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Pathogenic and non-pathogenic polyglutamine tracts have similar structural properties: towards a length-dependent toxicity gradient.
pubmed:affiliation
Department of Molecular Pathology, Institut de Génétique et Biologie Moléculaire et Cellulaire, UMR 7104-CNRS/INSERM/ULP, BP10142, 67404 Illkirch Cédex, CU de Strasbourg, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't