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Article

Ubiquitin ligase Nedd4 regulates the abundance and toxicity of mutant huntingtin.

JCI insight - 23 Feb 2026

Jeong Hyunkyung, Qin Yiyang, Xu Fangke, Trajkovic Katarina, Kim Myung Jong, Marotta Nicolas, Hamada Kana, Allada Ravi, Yang Su, Krainc Dimitri

Abstract excerpt

Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of CAG repeats in the gene encoding huntingtin. Since accumulation of mutant huntingtin (mHtt) leads to dysfunction of numerous cellular pathways and toxicity, reducing levels of the mutant protein represents a key therapeutic objective in HD. We found that ubiquitination of mHtt by E3 ubiquitin ligase Nedd4 promotes clearance of...

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Identifiers

PMID: 41729074
DOI: 10.1172/jci.insight.181013
PMCID: PMC12956003

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