ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Acute polyglutamine expression in inducible mouse model unravels ubiquitin/proteasome system impairment and permanent recovery attributable to aggregate formation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 94 citations in OpenAlex.
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- Rigor & Reproducibility: pH Adjustments of Papain with L-Cysteine Dissociation Solutions and Cell Media Using Phenol Red Spectrophotometry.Biosensors · 2025Article
- Review
- Cytosolic stress granules relieve the ubiquitin-proteasome system in the nuclear compartment.The EMBO journal · 2023Article
- The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington's Disease.Current neuropharmacology · 2023Review
- Passive immunization against phosphorylated tau improves features of Huntington's disease pathology.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Reduction in PA28αβ activation in HD mouse brain correlates to increased mHTT aggregation in cell models.PloS one · 2022Article
- Altered Cholesterol Homeostasis in Huntington's Disease.Frontiers in aging neuroscience · 2022Review
- Fluc-EGFP reporter mice reveal differential alterations of neuronal proteostasis in aging and disease.The EMBO journal · 2021Article
- Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington's disease.EMBO molecular medicine · 2021Article
- Prion-Associated Neurodegeneration Causes Both Endoplasmic Reticulum Stress and Proteasome Impairment in a Murine Model of Spontaneous Disease.International journal of molecular sciences · 2021Article
- Deubiquitinase USP7 contributes to the pathogenicity of spinal and bulbar muscular atrophy.The Journal of clinical investigation · 2021Article
- Nemo-like kinase reduces mutant huntingtin levels and mitigates Huntington's disease.Human molecular genetics · 2020Article
- Targeting Tau to Treat Clinical Features of Huntington's Disease.Frontiers in neurology · 2020Review
- Article
- Increased Levels of Rictor Prevent Mutant Huntingtin-Induced Neuronal Degeneration.Molecular neurobiology · 2018Article
- The ubiquitin conjugating enzyme Ube2W regulates solubility of the Huntington's disease protein, huntingtin.Neurobiology of disease · 2018Article
- Huntington's Disease: Mechanisms of Pathogenesis and Therapeutic Strategies.Cold Spring Harbor perspectives in medicine · 2017Review
- Proteomic Analysis After Status Epilepticus Identifies UCHL1 as Protective Against Hippocampal Injury.Neurochemical research · 2017Article
- PIN1 Modulates Huntingtin Levels and Aggregate Accumulation: AnFrontiers in cellular neuroscience · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The presence of intracellular ubiquitylated inclusions in neurodegenerative disorders and the role of the ubiquitin/proteasome system (UPS) in degrading abnormal hazardous proteins have given rise to the hypothesis that UPS-impairment underlies neurodegenerative processes. However, this remains controversial for polyglutamine disorders such as Huntington disease (HD). Whereas studies in cellular models have provided evidence in favor of UPS-impairment attributable to expression of the N-terminal fragment of mutant huntingtin (N-mutHtt), similar studies on mouse models failed to do so. Furthermore, we have recently shown that the increase in polyubiquitin conjugates reported in the brain of N-mutHtt mice occurs in the absence of a general UPS-impairment. In the present study we aim to clarify the potential of N-mutHtt to impair UPS function in vivo as well as the mechanisms by which neurons may adapt after prolonged exposure to N-mutHtt in genetic models. By combining UPS reporter mice with an inducible mouse model of HD, we demonstrate for the first time polyglutamine-induced global UPS-impairment in vivo. UPS-impairment occurred transiently after acute N-mutHtt expression and restoration correlated with appearance of inclusion bodies (IBs). Consistently, UPS recovery did not take place when IB formation was prevented through administration of N-mutHtt aggregation-inhibitors in both cellular and animal models. Finally, no UPS-impairment was detected in old mice constitutively expressing N-mutHtt despite the age-associated decrease in brain proteasome activity. Therefore, our data reconcile previous contradictory reports by showing that N-mutHtt can indeed impair UPS function in vivo and that N-mutHtt aggregation leads to long lasting restoration of UPS function.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.