ArticleCell death & disease2021
Nucleolar stress controls mutant Huntington toxicity and monitors Huntington's disease progression.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Illuminating ribosome biogenesis disorders through structural biology.RNA biology · 2026Review
- Nuclear dysfunction in aging and neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Analysis and design of disordered polypeptides with optimized sequence patterning properties.PLoS computational biology · 2026Article
- Temporal single-cell atlas of full-length Huntington's disease mouse model defines stage-specific signatures of corticostriatal dysfunction.Molecular neurodegeneration · 2026Article
- Analysis and design of disordered polypeptides with optimized sequence patterning properties.bioRxiv : the preprint server for biology · 2026Article
- Signaling to make human ribosomes: Connections between the cytoplasm and the nucleolus.Molecular cell · 2026Review
- Temporal single-cell atlas of full-length Huntington's disease mouse model defines stage-specific signatures of corticostriatal dysfunction.bioRxiv : the preprint server for biology · 2026Article
- The Expanding Role of Non-Coding RNAs in Neurodegenerative Diseases: From Biomarkers to Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Aberrant expression of the MID1 protein in neurons of Huntington's disease brain.Frontiers in genetics · 2026Article
- Transcriptome Study in Sicilian Patients with Huntington's Disease.Diagnostics (Basel, Switzerland) · 2025Article
- Absence of hippocampal pathology persists in the Q175DN mouse model of Huntington's disease despite elevated HTT aggregation.Journal of Huntington's disease · 2025Article
- Ribosomal DNA and Neurological Disorders.Current molecular medicine · 2025Review
- Two novel DnaJ chaperone proteins CG5001 and P58IPK regulate the pathogenicity of Huntington's disease related aggregates.Scientific reports · 2024Article
- Peripheral Blood Gene Expression Profiling Reveals Molecular Pathways Associated with Cervical Artery Dissection.International journal of molecular sciences · 2024Article
- Saccharomyces cerevisiae as a research tool for RNA-mediated human disease.Wiley interdisciplinary reviews. RNA · 2023Review
- Neuronal biomolecular condensates and their implications in neurodegenerative diseases.Frontiers in aging neuroscience · 2023Review
- Review
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Authors and funding
18 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcriptional and cellular-stress surveillance deficits are hallmarks of Huntington's disease (HD), a fatal autosomal-dominant neurodegenerative disorder caused by a pathological expansion of CAG repeats in the Huntingtin (HTT) gene. The nucleolus, a dynamic nuclear biomolecular condensate and the site of ribosomal RNA (rRNA) transcription, is implicated in the cellular stress response and in protein quality control. While the exact pathomechanisms of HD are still unclear, the impact of nucleolar dysfunction on HD pathophysiology in vivo remains elusive. Here we identified aberrant maturation of rRNA and decreased translational rate in association with human mutant Huntingtin (mHTT) expression. The protein nucleophosmin 1 (NPM1), important for nucleolar integrity and rRNA maturation, loses its prominent nucleolar localization. Genetic disruption of nucleolar integrity in vulnerable striatal neurons of the R6/2 HD mouse model decreases the distribution of mHTT in a disperse state in the nucleus, exacerbating motor deficits. We confirmed NPM1 delocalization in the gradually progressing zQ175 knock-in HD mouse model: in the striatum at a presymptomatic stage and in the skeletal muscle at an early symptomatic stage. In Huntington's patient skeletal muscle biopsies, we found a selective redistribution of NPM1, similar to that in the zQ175 model. Taken together, our study demonstrates that nucleolar integrity regulates the formation of mHTT inclusions in vivo, and identifies NPM1 as a novel, readily detectable peripheral histopathological marker of HD progression.
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