ArticlePloS one2012
Temporal separation of aggregation and ubiquitination during early inclusion formation in transgenic mice carrying the Huntington's disease mutation.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Interventionally targeting somatic CAG expansions can be a rapid disease-modifying therapeutic avenue: Preclinical evidence.bioRxiv : the preprint server for biology · 2025Article
- Spatiotemporal analysis of soluble aggregates and autophagy markers in the R6/2 mouse model.Scientific reports · 2021Article
- Quantification of Huntington's Disease Related Markers in the R6/2 Mouse Model.Frontiers in molecular neuroscience · 2020Article
- Strategies to Investigate Ubiquitination in Huntington's Disease.Frontiers in chemistry · 2020Review
- Antagonistic pleiotropy in mice carrying a CAG repeat expansion in the range causing Huntington's disease.Scientific reports · 2019Article
- Article
- Dynamic recruitment of ubiquitin to mutant huntingtin inclusion bodies.Scientific reports · 2018Article
- Article
- Transcriptional Dysregulation and Post-translational Modifications in Polyglutamine Diseases: From Pathogenesis to Potential Therapeutic Strategies.Frontiers in molecular neuroscience · 2018Review
- Article
- Protein misfolding specifies recruitment to cytoplasmic inclusion bodies.The Journal of cell biology · 2016Article
- Allele-Specific Reduction of the Mutant Huntingtin Allele Using Transcription Activator-Like Effectors in Human Huntington's Disease Fibroblasts.Cell transplantation · 2016Article
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- Article
- Prion-like transmission of neuronal huntingtin aggregates to phagocytic glia in the Drosophila brain.Nature communications · 2015Article
- Lymphocyte repertoire selection and intracellular self/non-self-discrimination: historical overview.Immunology and cell biology · 2015Review
- Ubiquitin-proteasome system involvement in Huntington's disease.Frontiers in molecular neuroscience · 2014Review
- Article
- Regulation of protein degradation by O-GlcNAcylation: crosstalk with ubiquitination.Molecular & cellular proteomics : MCP · 2013Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Abnormal insoluble ubiqitinated protein aggregates are found in the brains of Huntington's disease (HD) patients and in mice transgenic for the HTT mutation. Here, we describe the earliest stages of visible NII formation in brains of R6/2 mice killed between 2 and 6 weeks of age. We found that huntingtin-positive aggregates formed rapidly (within 24-48 hours) in a spatiotemporal manner similar to that we described previously for ubiquitinated inclusions. However, in most neurons, aggregates are not ubiquitinated when they first form. It has always been assumed that mutant huntingtin is recognised as 'foreign' and consequently ubiquitinated and targeted for degradation by the ubiquitin-proteasome system pathway. Our data, however, suggest that aggregation and ubiquitination are separate processes, and that mutant huntingtin fragment is not recognized as 'abnormal' by the ubiquitin-proteasome system before aggregation. Rather, mutant Htt appears to aggregate before it is ubiquitinated, and then either aggregated huntingtin is ubiquitinated or ubiquitinated proteins are recruited into aggregates. Our findings have significant implications for the role of the ubiquitin-proteasome system in the formation of aggregates, as they suggest that this system is not involved until after the first aggregates form.
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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.