ArticleQuarterly reviews of biophysics2016
Delayed emergence of subdiffraction-sized mutant huntingtin fibrils following inclusion body formation.
Article in Quarterly reviews of biophysics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 72 citations in OpenAlex.
- Large-scale visualization of α-synuclein oligomers in Parkinson's disease brain tissue.Nature biomedical engineering · 2026Article
- Chaperonin in health and disease.Molecular biomedicine · 2026Review
- Probing How Anti-huntingtin Antibodies Bind the Fibrillar Fuzzy Coat Using Solid-State NMR.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Single-Molecule Orientation Imaging Reveals the Nano-Architecture of Amyloid Fibrils Undergoing Growth and Decay.Nano letters · 2024Article
- BDNF and TRiC-inspired reagent rescue cortical synaptic deficits in a mouse model of Huntington's disease.Neurobiology of disease · 2024Article
- Single-Molecule Orientation Imaging Reveals the Nano-Architecture of Amyloid Fibrils Undergoing Growth and Decay.bioRxiv : the preprint server for biology · 2024Article
- The interwoven fibril-like structure of amyloid-beta plaques in mouse brain tissue visualized using super-resolution STED microscopy.Cell & bioscience · 2023Article
- Dynamic Mode Decomposition of Fluorescence Loss in Photobleaching Microscopy Data for Model-Free Analysis of Protein Transport and Aggregation in Living Cells.Sensors (Basel, Switzerland) · 2022Article
- Extraction of Hidden Science from Nanoscale Images.The journal of physical chemistry. C, Nanomaterials and interfaces · 2022Article
- Small, Seeding-Competent Huntingtin Fibrils Are Prominent Aggregate Species in Brains of zQ175 Huntington's Disease Knock-in Mice.Frontiers in neuroscience · 2021Article
- Lipid headgroups alter huntingtin aggregation on membranes.Biochimica et biophysica acta. Biomembranes · 2021Article
- Live-Cell Imaging and Quantification of PolyQ Aggregates by Stimulated Raman Scattering of Selective Deuterium Labeling.ACS central science · 2020Article
- Differentiation Drives Widespread Rewiring of the Neural Stem Cell Chaperone Network.Molecular cell · 2020Article
- Nucleation Inhibition of Huntingtin Protein (htt) by Polyproline PPII Helices: A Potential Interaction with the N-Terminal α-Helical Region of Htt.Biochemistry · 2020Article
- Tissue Clearing and Expansion Methods for Imaging Brain Pathology in Neurodegeneration: From Circuits to Synapses and Beyond.Frontiers in neuroscience · 2020Review
- Mutational analysis implicates the amyloid fibril as the toxic entity in Huntington's disease.Neurobiology of disease · 2018Article
- A discontinuous Galerkin model for fluorescence loss in photobleaching of intracellular polyglutamine protein aggregates.BMC biophysics · 2018Article
- Nano-Architectural Approaches for Improved Intracortical Interface Technologies.Frontiers in neuroscience · 2018Review
- Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core.Nature communications · 2017Article
- Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Aberrant aggregation of improperly folded proteins is the hallmark of several human neurodegenerative disorders, including Huntington's Disease (HD) with autosomal-dominant inheritance. In HD, expansion of the CAG-repeat-encoded polyglutamine (polyQ) stretch beyond ~40 glutamines in huntingtin (Htt) and its N-terminal fragments leads to the formation of large (up to several μm) globular neuronal inclusion bodies (IBs) over time. We report direct observations of aggregating Htt exon 1 in living and fixed cells at enhanced spatial resolution by stimulated emission depletion (STED) microscopy and single-molecule super-resolution optical imaging. Fibrils of Htt exon 1 arise abundantly across the cytosolic compartment and also in neuritic processes only after nucleation and aggregation into a fairly advanced stage of growth of the prominent IB have taken place. Structural characterizations of fibrils by STED show a distinct length cutoff at ~1·5 µm and reveal subsequent coalescence (bundling/piling). Cytosolic fibrils are observed even at late stages in the process, side-by-side with the mature IB. Htt sequestration into the IB, which in neurons has been argued to be a cell-protective phenomenon, thus appears to saturate and over-power the cellular degradation systems and leaves cells vulnerable to further aggregation producing much smaller, potentially toxic, conformational protein species of which the fibrils may be comprised. We further found that exogenous delivery of the apical domain of the chaperonin subunit CCT1 to the cells via the cell medium reduced the aggregation propensity of mutant Htt exon 1 in general, and strongly reduced the occurrence of such late-stage fibrils in particular.
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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.