Macromolecular crowding in solution alters huntingtin interaction and aggregation at interfaces.

ABSTRACT: Huntington's disease (HD) is a fatal neurodegenerative disease caused by an extended polyglutamine (polyQ) domain within the first exon of the huntingtin protein (htt). PolyQ expansion directly invokes the formation of a heterogenous mixture of toxic htt aggregates, including fibrils and oligomers. While htt is a cytosolic protein, it also associates with numerous membranous surfaces within the cell, leading to altered organelle morphology and dysfunction. Here, the impact of macromolecular crowding on htt aggregation in bulk solution and at solid/liquid or membrane/liquid interfaces was investigated. Dextran, Ficoll, and polyethylene glycol (PEG) were used as crowding agents. In bulk solution, crowding enhanced the heterogeneity of non-fibrillar aggregate species formed in a crowder depen

SUBMITTER: Groover SE 

PROVIDER: S-EPMC8429182 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature