Chaperone-mediated remodelling of mutant huntingtin.

Authors

Kunal Gharat, Janine Kirstein

Published in

Philosophical transactions of the Royal Society of London. Series B, Biological sciences. Volume 381. Issue 1960. Oct 01, 2026.

Abstract

Huntington's disease is caused by the trinucleotide repeat CAG expansion in the huntingtin gene, resulting in an N-terminal polyglutamine (polyQ) tract that renders the huntingtin protein (HTT) prone to misfolding and aggregation. Although polyQ expansion is an intrinsic driver of aggregation, the folding trajectory of HTT is strongly shaped by molecular chaperones that detect all conformational entities of HTT and as such bind to soluble HTT and suppress β-sheet formation, target HTT for proteasomal degradation and resolubilize HTT fibrils by disaggregation. This review summarizes recent in vitro and in vivo data on the role of molecular chaperones in the HTTExon1 folding landscape and its cooperation with the proteolytic pathways. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.

PMID:
42817626
Bibliographic data and abstract were imported from PubMed on 01 Oct 2026.

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