ArticleThe Journal of biological chemistry2012
Protein misfolding detected early in pathogenesis of transgenic mouse model of Huntington disease using amyloid seeding assay.
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 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- N-terminal modifications as fate switches in neurodegeneration: a mechanistic review.Frontiers in aging neuroscience · 2026Review
- Huntington's disease: lessons from prion disorders.Journal of neurology · 2021Article
- Structural insight into transmissive mutant huntingtin species by correlative light and electron microscopy and cryo-electron tomography.Biochemical and biophysical research communications · 2021Article
- Proteopathic Seed Amplification Assays for Neurodegenerative Disorders.Clinics in laboratory medicine · 2020Review
- Testing Amyloid Cross-Toxicity in the Vertebrate Brain.ACS omega · 2020Article
- Engineered Extracellular Vesicles/Exosomes as a New Tool against Neurodegenerative Diseases.Pharmaceutics · 2020Review
- Progress in developing transgenic monkey model for Huntington's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- Review
- Prions: Beyond a Single Protein.Clinical microbiology reviews · 2016Review
- Polyglutamine Aggregation in Huntington Disease: Does Structure Determine Toxicity?Molecular neurobiology · 2015Review
- Comparative study of naturally occurring huntingtin fragments in Drosophila points to exon 1 as the most pathogenic species in Huntington's disease.Human molecular genetics · 2015Article
- Proteopathic tau seeding predicts tauopathy in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Monomeric, oligomeric and polymeric proteins in huntington disease and other diseases of polyglutamine expansion.Brain sciences · 2014Article
- Intrabodies as neuroprotective therapeutics.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2013Review
- Huntington's disease induced cardiac amyloidosis is reversed by modulating protein folding and oxidative stress pathways in the Drosophila heart.PLoS genetics · 2013Article
- Kinetically competing huntingtin aggregation pathways control amyloid polymorphism and properties.Biochemistry · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Huntington disease (HD) is one of several fatal neurodegenerative disorders associated with misfolded proteins. Here, we report a novel method for the sensitive detection of misfolded huntingtin (HTT) isolated from the brains of transgenic (Tg) mouse models of HD and humans with HD using an amyloid seeding assay (ASA), which is based on the propensity of misfolded proteins to act as a seed and shorten the nucleation-associated lag phase in the kinetics of amyloid formation in vitro. Using synthetic polyglutamine peptides as the substrate for amyloid formation, we found that partially purified misfolded HTT obtained from end-stage brain tissue of two Tg HD mouse models and brain tissue of post-mortem human HD patients was capable of specifically accelerating polyglutamine amyloid formation compared with unseeded reactions and controls. Alzheimer and prion disease brain tissues did not do so, demonstrating the specificity of the ASA. It is unclear whether early intermediates or later conformational species in the protein misfolding process act as seeds in the ASA for HD. However, we were able to detect misfolded protein in the brains of YAC128 mice early in disease pathogenesis (11 weeks of age), whereas large inclusion bodies have not been observed in the brains of these mice by histology until 78 weeks of age, much later in the pathogenic process. The sensitive detection of misfolded HTT protein early in the disease pathogenesis in the YAC128 Tg mouse model strengthens the argument for a causative role of protein misfolding in HD.
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Registered trials
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