Prefibrillar huntingtin oligomers isolated from HD brain potently seed amyloid formation.

Autor: Morozova OA; Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA., Gupta S; Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA., Colby DW; Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA. Electronic address: colby@udel.edu.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2015 Jul 08; Vol. 589 (15), pp. 1897-903. Date of Electronic Publication: 2015 May 30.
DOI: 10.1016/j.febslet.2015.05.041
Abstrakt: Many neurodegenerative diseases are associated with deposits of aggregated protein in the brain. The molecular pathways through which soluble proteins misfold to form amyloids and large protein aggregates often include diverse oligomeric species, only some of which progress to the amyloid state. Here we show that prefibrillar huntingtin (HTT) oligomers, isolated from Huntington's disease (HD) affected human brain samples or mouse models, stimulate polyglutamine amyloid formation. Fibrillar HTT oligomers have been shown to be unstable under denaturing conditions and appear not to lead to amyloid formation. Here we show that prefibrillar HTT oligomers are remarkably stable and are potent seeds of polyglutamine amyloid formation. Therefore, our findings help to dissect the complex molecular pathway of HTT misfolding.
(Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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