ArticleNature cell biology2024
Polyglutamine-mediated ribotoxicity disrupts proteostasis and stress responses in Huntington's disease.
Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- 5PSeq Explorer: interactive analysis of co-translational mRNA decay and ribosome dynamics.RNA biology · 2026Article
- Nuclear membrane disruption in neurodegenerative diseases: Emerging perspectives.Neural regeneration research · 2026Article
- Uncovering hidden protein networks in Huntington's disease: implications for pathogenesis and therapy.Molecular biology reports · 2026Review
- eIF5A and polyamines restrict mRNA levels in response to ribosome stalls.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Microbiota-gut-brain axis and bile acids-driven neuromodulation.Neural regeneration research · 2026Article
- Human-specific sequence features in HTT exon 1 promote toxic misprocessing via splicing factor SRSF7.Nature communications · 2026Article
- A Age Related Vascular Senescence: Mystery of Blood-brain Barrier Dysfunction in Neurodegeneration.Molecular neurobiology · 2026Review
- Huntingtin (HTT) interactome in regulation of DNA repair/remodeling and RNA processing pathways.Life science alliance · 2026Article
- Single-cell transcriptomics and mouse model phenotyping for biomarker screen of peripheral blood in Huntington's disease.Scientific reports · 2026Article
- eIF5A coordinates the transcription and translation of its target genes.Cellular and molecular life sciences : CMLS · 2026Article
- Ribosome Molecular Aging Shapes Translation Dynamics.bioRxiv : the preprint server for biology · 2026Article
- Article
- The Expanding Role of Non-Coding RNAs in Neurodegenerative Diseases: From Biomarkers to Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Axonal Eif5a hypusination controls local translation and mitigates defects in FUS-ALS.Nature neuroscience · 2026Article
- Interplay Among Synaptic Glutamate Release and Excitotoxicity: Neuronal Damage and Graphene-Based Materials Related Protection.Life (Basel, Switzerland) · 2025Review
- FGF14 repeat length and mosaic interruptions: modifiers of spinocerebellar ataxia 27B?Brain : a journal of neurology · 2025Article
- K29-Linked Ubiquitination of Transcription Regulators Controls Cell Proliferation in the Unfolded Protein Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Translational regulation in stress biology.Nature cell biology · 2025Review
- Sertraline treatment prevents motor dysfunction in a Huntington's disease mouse model and functional decline in patients.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Huntington's disease (HD) is a neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat in the Huntingtin (HTT) gene, encoding a homopolymeric polyglutamine (polyQ) tract. Although mutant HTT (mHTT) protein is known to aggregate, the links between aggregation and neurotoxicity remain unclear. Here we show that both translation and aggregation of wild-type HTT and mHTT are regulated by a stress-responsive upstream open reading frame and that polyQ expansions cause abortive translation termination and release of truncated, aggregation-prone mHTT fragments. Notably, we find that mHTT depletes translation elongation factor eIF5A in brains of symptomatic HD mice and cultured HD cells, leading to pervasive ribosome pausing and collisions. Loss of eIF5A disrupts homeostatic controls and impairs recovery from acute stress. Importantly, drugs that inhibit translation initiation reduce premature termination and mitigate this escalating cascade of ribotoxic stress and dysfunction in HD.
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