Nanoscale studies link amyloid maturity with polyglutamine diseases onset

The presence of expanded poly-glutamine (polyQ) repeats in proteins is directly linked to the pathogenesis of several neurodegenerative diseases, including Huntington's disease. However, the molecular and structural basis underlying the increased toxicity of aggregates formed by proteins containing expanded polyQ repeats remain poorly understood, in part due to the size and morphological heterogeneity of the aggregates they form in vitro. To address this knowledge gap and technical limitations, we investigated the structural, mechanical and morphological properties of fibrillar aggregates at the single molecule and nanometer scale using the first exon of the Huntingtin protein as a model system (Exon1). Our findings demonstrate a direct correlation of the morphological and mechanical properties of Exon1 aggregates with their structural organization at the single aggregate and nanometric scale and provide novel insights into the molecular and structural basis of Huntingtin Exon1 aggregation and toxicity.


Published in:
Scientific Reports, 6, 31155
Year:
Aug 01 2016
Publisher:
London, Nature Publishing Group
ISSN:
2045-2322
Note:
This article is licensed under a Creative Commons Attribution 4.0 International License
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Note: The status of this file is: Anyone


 Record created 2016-10-18, last modified 2020-10-27

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