ArticleThe Journal of biological chemistry2012
Native mutant huntingtin in human brain: evidence for prevalence of full-length monomer.
Article in The Journal of biological chemistry, 2012. 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, 27 citations in OpenAlex.
- Mutant huntingtin exon 1 protein detected in mouse brain with neoepitope antibody: effects of CAG repeat expansion, MutS Homolog 3 silencing and aggregation.Brain communications · 2025Article
- A novel HDAC6 inhibitor, CKD-504, is effective in treating preclinical models of huntington's disease.BMB reports · 2023Article
- Allele-specific silencing of the gain-of-function mutation in Huntington's disease using CRISPR/Cas9.JCI insight · 2022Article
- PAM-altering SNP-based allele-specific CRISPR-Cas9 therapeutic strategies for Huntington's disease.Molecular therapy. Methods & clinical development · 2022Article
- Huntingtin and Its Partner Huntingtin-Associated Protein 40: Structural and Functional Considerations in Health and Disease.Journal of Huntington's disease · 2022Review
- Founder Effects of Spinocerebellar Ataxias in the American Continents and the Caribbean.Cerebellum (London, England) · 2020Review
- Article
- A patient-derived cellular model for Huntington's disease reveals phenotypes at clinically relevant CAG lengths.Molecular biology of the cell · 2018Article
- Article
- Suppression of MAPK11 or HIPK3 reduces mutant Huntingtin levels in Huntington's disease models.Cell research · 2017Article
- A toxic mutant huntingtin species is resistant to selective autophagy.Nature chemical biology · 2017Article
- Review
- Folding Landscape of Mutant Huntingtin Exon1: Diffusible Multimers, Oligomers and Fibrils, and No Detectable Monomer.PloS one · 2016Article
- Increased SNARE Protein-Protein Interactions in Orbitofrontal and Anterior Cingulate Cortices in Schizophrenia.Biological psychiatry · 2015Article
- Primary cilia and autophagic dysfunction in Huntington's disease.Cell death and differentiation · 2015Review
- Article
- Development of an ELISA assay for the quantification of soluble huntingtin in human blood cells.BMC biochemistry · 2013Article
- Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Huntington disease (HD) is caused by polyglutamine expansion in the N terminus of huntingtin (htt). Analysis of human postmortem brain lysates by SDS-PAGE and Western blot reveals htt as full-length and fragmented. Here we used Blue Native PAGE (BNP) and Western blots to study native htt in human postmortem brain. Antisera against htt detected a single band broadly migrating at 575-850 kDa in control brain and at 650-885 kDa in heterozygous and Venezuelan homozygous HD brains. Anti-polyglutamine antisera detected full-length mutant htt in HD brain. There was little htt cleavage even if lysates were pretreated with trypsin, indicating a property of native htt to resist protease cleavage. A soluble mutant htt fragment of about 180 kDa was detected with anti-htt antibody Ab1 (htt-(1-17)) and increased when lysates were treated with denaturants (SDS, 8 M urea, DTT, or trypsin) before BNP. Wild-type htt was more resistant to denaturants. Based on migration of in vitro translated htt fragments, the 180-kDa segment terminated ≈htt 670-880 amino acids. If second dimension SDS-PAGE followed BNP, the 180-kDa mutant htt was absent, and 43-50 kDa htt fragments appeared. Brain lysates from two HD mouse models expressed native full-length htt; a mutant fragment formed if lysates were pretreated with 8 M urea + DTT. Native full-length mutant htt in embryonic HD(140Q/140Q) mouse primary neurons was intact during cell death and when cell lysates were exposed to denaturants before BNP. Thus, native mutant htt occurs in brain and primary neurons as a soluble full-length monomer.
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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.