ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Mutant huntingtin causes context-dependent neurodegeneration in mice with Huntington's disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 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
121 citing papers in PubMed, 256 citations in OpenAlex.
- Animal models of Huntington's disease. Pros and cons.Brain, behavior, & immunity - health · 2025Review
- Natural products proposed for the management of Huntington's disease (HD): a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Huntingtin preserves mitochondrial genome integrity in neurons, which is impaired in Huntington's disease.bioRxiv : the preprint server for biology · 2025Article
- Regulation of Mutant Huntingtin Mitochondrial Toxicity by Phosphomimetic Mutations within Its N-Terminal Region.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Ferroptosis in central nervous system injuries: molecular mechanisms, diagnostic approaches, and therapeutic strategies.Frontiers in cellular neuroscience · 2025Review
- Developmental and physiological impacts of pathogenic human huntingtin protein in the nervous system.Neurobiology of disease · 2024Article
- Neuroinflammatory Proteins in Huntington's Disease: Insights into Mechanisms, Diagnosis, and Therapeutic Implications.International journal of molecular sciences · 2024Review
- Luteolin as potential treatment for Huntington's disease: Insights from a transgenic mouse model.CNS neuroscience & therapeutics · 2024Article
- Abnormal outer and inner retina in a mouse model of Huntington's disease with age.Frontiers in aging neuroscience · 2024Article
- The N17 domain of huntingtin as a multifaceted player in Huntington's disease.Frontiers in molecular biosciences · 2024Review
- Mitochondrial Bioenergy in Neurodegenerative Disease: Huntington and Parkinson.International journal of molecular sciences · 2023Review
- Single-nuclei transcriptome analysis of Huntington disease iPSC and mouse astrocytes implicates maturation and functional deficits.iScience · 2023Article
- Contribution of Glial Cells to Polyglutamine Diseases: Observations from Patients and Mouse Models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington's Disease.Current neuropharmacology · 2023Review
- Cogs in the autophagic machine-equipped to combat dementia-prone neurodegenerative diseases.Frontiers in molecular neuroscience · 2023Review
- The protective role of exercise against age-related neurodegeneration.Ageing research reviews · 2022Review
- Neuroinflammation in Huntington's Disease: A Starring Role for Astrocyte and Microglia.Current neuropharmacology · 2022Review
- Neuroinflammation in Huntington's disease: From animal models to clinical therapeutics.Frontiers in immunology · 2022Review
- Mitochondrial membranes modify mutant huntingtin aggregation.Biochimica et biophysica acta. Biomembranes · 2021Article
- Epigenetic regulation in Huntington's disease.Neurochemistry international · 2021Review
61 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
6 authors at 1 institution in 1 country.
Funding
Abstract
Huntington's disease (HD) mouse models that express N-terminal huntingtin fragments show rapid disease progression and have been used for developing therapeutics. However, light microscopy reveals no significant neurodegeneration in these mice. It remains unclear how mutant huntingtin induces neurodegeneration. Using caspase staining, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling, and electron microscopy, we observed that N171-82Q mice, which express the first 171 aa of mutant huntingtin, displayed more degenerated neurons than did other HD mouse models. The neurodegeneration was also evidenced by increased immunostaining for glial fibrillary acidic protein and ultrastructural features of apoptosis. R6/2 mice, which express exon 1 of mutant huntingtin, showed dark, nonapoptotic neurons and degenerated mitochondria associated with mutant huntingtin. In HD repeat knock-in mice (HdhCAG150), which express full-length mutant huntingtin, degenerated cytoplasmic organelles were found in both axons and neuronal cell bodies in association with mutant huntingtin that was not labeled by an antibody to huntingtin amino acids 342-456. Transfection of cultured cells with mutant huntingtin revealed that an N-terminal huntingtin fragment (amino acids 1-208 plus a 120 glutamine repeat) caused a greater increase in caspase activity than did exon 1 huntingtin and longer huntingtin fragments. These results suggest that context-dependent neurodegeneration in HD may be mediated by different N-terminal huntingtin fragments. In addition, this study has identified neurodegenerative markers for the evaluation of therapeutic treatments in HD mouse models.
Indexed as
Identifiers
12657678PMC6742008W1514558092What 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.