ArticleThe Journal of cell biology2003
Huntingtin forms toxic NH2-terminal fragment complexes that are promoted by the age-dependent decrease in proteasome activity.
Article in The Journal of cell biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
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Who cites it
79 citing papers in PubMed, 159 citations in OpenAlex.
- Oligodendroglial Mutant Huntingtin Contributes to Neuroinflammation in Huntington's Disease Mice.Neuroscience bulletin · 2026Article
- Review
- DurableMolecular therapy. Nucleic acids · 2025Article
- Progressive degeneration in a new Drosophila model of spinocerebellar ataxia type 7.Scientific reports · 2024Article
- Proteotoxic stress and the ubiquitin proteasome system.Seminars in cell & developmental biology · 2024Review
- Interactions Between the Ubiquitin-Proteasome System, Nrf2, and the Cannabinoidome as Protective Strategies to Combat Neurodegeneration: Review on Experimental Evidence.Neurotoxicity research · 2024Review
- A method for the analysis of the oligomerization profile of the Huntington's disease-associated, aggregation-prone mutant huntingtin protein by isopycnic ultracentrifugation.Frontiers in molecular biosciences · 2024Article
- Oleuropein enhances proteasomal activity and reduces mutant huntingtin-induced cytotoxicity.Frontiers in pharmacology · 2024Article
- Progressive degeneration in a newResearch square · 2023Article
- FLIM-FRET Investigation of Heterogeneous Huntingtin Aggregation in HeLa Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Widespread alterations in microRNA biogenesis in human Huntington's disease putamen.Acta neuropathologica communications · 2022Article
- Calpain-mediated proteolysis as driver and modulator of polyglutamine toxicity.Frontiers in molecular neuroscience · 2022Review
- A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases.Frontiers in molecular neuroscience · 2022Review
- Inhibition of p38 Mitogen-Activated Protein Kinase Ameliorates HAP40 Depletion-Induced Toxicity and Proteasomal Defect in Huntington's Disease Model.Molecular neurobiology · 2021Article
- When nature's robots go rogue: exploring protein homeostasis dysfunction and the implications for understanding human aging disease pathologies.Expert review of proteomics · 2018Review
- The Ubiquitin Receptor ADRM1 Modulates HAP40-Induced Proteasome Activity.Molecular neurobiology · 2017Article
- N-terminal Huntingtin Knock-In Mice: Implications of Removing the N-terminal Region of Huntingtin for Therapy.PLoS genetics · 2016Article
- The Role of Autophagy, Mitophagy and Lysosomal Functions in Modulating Bioenergetics and Survival in the Context of Redox and Proteotoxic Damage: Implications for Neurodegenerative Diseases.Aging and disease · 2016Review
- Polyglutamine Aggregation in Huntington Disease: Does Structure Determine Toxicity?Molecular neurobiology · 2015Review
- Multidrug resistance protein 1 reduces the aggregation of mutant huntingtin in neuronal cells derived from the Huntington's disease R6/2 model.Scientific reports · 2015Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Although NH2-terminal mutant huntingtin (htt) fragments cause neurological disorders in Huntington's disease (HD), it is unclear how toxic htt fragments are generated and contribute to the disease process. Here, we report that complex NH2-terminal mutant htt fragments smaller than the first 508 amino acids were generated in htt-transfected cells and HD knockin mouse brains. These fragments constituted neuronal nuclear inclusions and appeared before neurological symptoms. The accumulation and aggregation of these htt fragments were associated with an age-dependent decrease in proteasome activity and were promoted by inhibition of proteasome activity. These results suggest that decreased proteasome activity contributes to late onset htt toxicity and that restoring the ability to remove NH2-terminal fragments will provide a more effective therapy for HD than inhibiting their production.
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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.