ArticleACS chemical biology2014
Super-resolution fluorescence of huntingtin reveals growth of globular species into short fibers and coexistence of distinct aggregates.
Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 77 citations in OpenAlex.
- Seeing the Unseen: Super-Resolution Microscopy in Protein Aggregation Research.Chemical & biomedical imaging · 2026Review
- Kinetic Mechanism of Substoichiometric Inhibition of Huntingtin Exon-1 Protein Aggregation by Selenium Nanoparticles.Small science · 2025Article
- Characterizing heterogeneity in amyloid formation processes.Current opinion in structural biology · 2024Review
- Developmental and physiological impacts of pathogenic human huntingtin protein in the nervous system.Neurobiology of disease · 2024Article
- Polyglutamine-mediated ribotoxicity disrupts proteostasis and stress responses in Huntington's disease.Nature cell biology · 2024Article
- Solid-state nuclear magnetic resonance in the structural study of polyglutamine aggregation.Biochemical Society transactions · 2024Review
- Quantitative NMR analysis of the kinetics of prenucleation oligomerization and aggregation of pathogenic huntingtin exon-1 protein.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- NMR spectroscopy, excited states and relevance to problems in cell biology - transient pre-nucleation tetramerization of huntingtin and insights into Huntington's disease.Journal of cell science · 2022Article
- Selective observation of semi-rigid non-core residues in dynamically complex mutant huntingtin protein fibrils.Journal of structural biology: X · 2022Article
- Recent Microscopy Advances and the Applications to Huntington's Disease Research.Journal of Huntington's disease · 2022Review
- Cryo-electron tomography provides topological insights into mutant huntingtin exon 1 and polyQ aggregates.Communications biology · 2021Article
- High spatial-resolution imaging of label-freeThe Analyst · 2021Article
- Site-Specific Phosphorylation of Huntingtin Exon 1 Recombinant Proteins Enabled by the Discovery of Novel Kinases.Chembiochem : a European journal of chemical biology · 2021Article
- Protofilament Structure and Supramolecular Polymorphism of Aggregated Mutant Huntingtin Exon 1.Journal of molecular biology · 2020Article
- Kinetics of Fast Tetramerization of the Huntingtin Exon 1 Protein Probed by Concentration-Dependent On-ResonanceThe journal of physical chemistry letters · 2020Article
- Genome Dashboards: Framework and Examples.Biophysical journal · 2020Article
- Abrogation of prenucleation, transient oligomerization of the Huntingtin exon 1 protein by human profilin I.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Tissue Clearing and Expansion Methods for Imaging Brain Pathology in Neurodegeneration: From Circuits to Synapses and Beyond.Frontiers in neuroscience · 2020Review
- Conformational studies of pathogenic expanded polyglutamine protein deposits from Huntington's disease.Experimental biology and medicine (Maywood, N.J.) · 2019Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Polyglutamine-expanded huntingtin, the protein encoded by HTT mutations associated with Huntington's disease, forms aggregate species in vitro and in vivo. Elucidation of the mechanism of growth of fibrillar aggregates from soluble monomeric protein is critical to understanding the progression of Huntington's disease and to designing therapeutics for the disease, as well as for aggregates implicated in Alzheimer's and Parkinson's diseases. We used the technique of multicolor single-molecule, super-resolution fluorescence imaging to characterize the growth of huntingtin exon 1 aggregates. The huntingtin exon 1 aggregation followed a pathway from exclusively spherical or globular species of ∼80 nm to fibers ∼1 μm in length that increased in width, but not length, over time with the addition of more huntingtin monomers. The fibers further aggregated with one another into aggregate assemblies of increasing size. Seeds created by sonication, which were comparable in shape and size to the globular species in the pathway, were observed to grow through multidirectional elongation into fibers, suggesting a mechanism for growth of globular species into fibers. The single-molecule sensitivity of our approach made it possible to characterize the aggregation pathway across a large range of size scales, from monomers to fiber assemblies, and revealed the coexistence of different aggregate species (globular species, fibers, fiber assemblies) even at late time points.
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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.