Evidence map›Paper›PMID 41729074›Full record

ArticleJCI insight2026

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

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

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Hyunkyung JeongDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Yiyang QinGuangdong Provincial Key Laboratory of Non-human Primate Research, Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China.
Fangke XuDepartment of Neurobiology, Northwestern University, Evanston, Illinois, USA.
Katarina TrajkovicDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Myung Jong KimDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Nicolas MarottaDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Kana HamadaDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Ravi AlladaDepartment of Neurobiology, Northwestern University, Evanston, Illinois, USA.
Su YangGuangdong Provincial Key Laboratory of Non-human Primate Research, Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China.
Dimitri KraincDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 the mutant protein. Knockdown of Nedd4 increased toxicity of mHtt in mouse primary neurons and in a fly model of HD, suggesting the protective role of Nedd4. Importantly, levels of Nedd4 were decreased in mHtt-expressing neurons through impaired mTORC1 activity, suggesting a feedback loop of mHtt accumulation and Nedd4 reduction that leads to accumulation and, ultimately, toxicity of mHtt. These findings suggest that restoring Nedd4 activity may offer a novel therapeutic opportunity for HD.

Indexed as

Huntingtin ProteinHuntington DiseaseNedd4 Ubiquitin Protein LigasesAnimalsDisease Models, AnimalDrosophilaHumansMiceMutationNeuronsUbiquitinationHTT protein, humanHtt protein, mouseHuntingtin ProteinNedd4 protein, humanNedd4 protein, mouseNedd4 Ubiquitin Protein LigasesCell biologyNeurodegenerationNeuroscience

Identifiers

PMID41729074
PMCPMC12956003

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.