ArticleMolecular neurodegeneration2015
Making (anti-) sense out of huntingtin levels in Huntington disease.
Article in Molecular neurodegeneration, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Accurate Quantification of Mutant and Wild-Type polyQ Proteins Using Simple Western Capillary Immunoassays.Molecular neurobiology · 2025Article
- Huntingtin HTT1a is generated in a CAG repeat-length-dependent manner in human tissues.Molecular medicine (Cambridge, Mass.) · 2024Article
- Mutant huntingtin protein decreases with CAG repeat expansion: implications for therapeutics and bioassays.Brain communications · 2024Article
- Extracellular vesicles improve GABAergic transmission in Huntington's disease iPSC-derived neurons.Theranostics · 2023Article
- Differential expression and roles of Huntingtin and Huntingtin-associated protein 1 in the mouse and primate brains.Cellular and molecular life sciences : CMLS · 2022Article
- Defective mitochondria-lysosomal axis enhances the release of extracellular vesicles containing mitochondrial DNA and proteins in Huntington's disease.Journal of extracellular biology · 2022Article
- Neural Network Aided Detection of Huntington Disease.Journal of clinical medicine · 2022Article
- Review
- Review
- Assessing average somatic CAG repeat instability at the protein level.Scientific reports · 2019Article
- Juvenile Huntington's Disease Skin Fibroblasts Respond with Elevated Parkin Level and Increased Proteasome Activity as a Potential Mechanism to Counterbalance the Pathological Consequences of Mutant Huntingtin Protein.International journal of molecular sciences · 2019Article
- The effects of huntingtin-lowering: what do we know so far?Degenerative neurological and neuromuscular disease · 2019Review
- The pathogenic exon 1 HTT protein is produced by incomplete splicing in Huntington's disease patients.Scientific reports · 2017Article
- Novel allele-specific quantification methods reveal no effects of adult onset CAG repeats on HTT mRNA and protein levels.Human molecular genetics · 2017Article
- An enhanced Q175 knock-in mouse model of Huntington disease with higher mutant huntingtin levels and accelerated disease phenotypes.Human molecular genetics · 2016Article
- Allele-Specific Reduction of the Mutant Huntingtin Allele Using Transcription Activator-Like Effectors in Human Huntington's Disease Fibroblasts.Cell transplantation · 2016Article
- Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2016Review
- Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuntington disease (HD) is an autosomal dominant neurodegenerative disorder, characterized by motor, psychiatric and cognitive symptoms. HD is caused by a CAG repeat expansion in the first exon of the HTT gene, resulting in an expanded polyglutamine tract at the N-terminus of the huntingtin protein. Typical disease onset is around mid-life (adult-onset HD) whereas onset below 21 years is classified as juvenile HD. While much research has been done on the underlying HD disease mechanisms, little is known about regulation and expression levels of huntingtin RNA and protein.
resultsIn this study we used 15 human post-mortem HD brain samples to investigate the expression of wild-type and mutant huntingtin mRNA and protein. In adult-onset HD brain samples, there was a small but significantly lower expression of mutant huntingtin mRNA compared to wild-type huntingtin mRNA, while wild-type and mutant huntingtin protein expression levels did not differ significantly. Juvenile HD subjects did show a lower expression of mutant huntingtin protein compared to wild-type huntingtin protein. Our results in HD brain and fibroblasts suggest that protein aggregation does not affect levels of huntingtin RNA and protein. Additionally, we did not find any evidence for a reduced expression of huntingtin antisense in fibroblasts derived from a homozygous HD patient.
conclusionsWe found small differences in allelic huntingtin mRNA levels in adult-onset HD brain, with significantly lower mutant huntingtin mRNA levels. Wild-type and mutant huntingtin protein were not significantly different in adult-onset HD brain samples. Conversely, in juvenile HD brain samples mutant huntingtin protein levels were lower compared with wild-type huntingtin, showing subtle differences between juvenile HD and adult-onset HD. Since most HD model systems harbor juvenile repeat expansions, our results suggest caution with the interpretation of huntingtin mRNA and protein studies using HD cell and animal models with such long repeats. Furthermore, our huntingtin antisense results in homozygous HD cells do not support reduced huntingtin antisense expression due to an expanded CAG repeat.
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