ArticleeLife2016
Control of the structural landscape and neuronal proteotoxicity of mutant Huntingtin by domains flanking the polyQ tract.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 90 citations in OpenAlex.
- Lipid composition controls the huntingtin exon 1 membrane-association and differentially modulates its flanking regions' dynamics.Protein science : a publication of the Protein Society · 2026Article
- Progressively reduced cerebral oxygen metabolism and elevated plasma NfL levels in the zQ175DN mouse model of Huntington's disease.Experimental neurology · 2025Article
- Kinetic Mechanism of Substoichiometric Inhibition of Huntingtin Exon-1 Protein Aggregation by Selenium Nanoparticles.Small science · 2025Article
- Multiscale Simulations Elucidate the Mechanism of Polyglutamine Aggregation and the Role of Flanking Domains in Fibril Polymorphism.The journal of physical chemistry. B · 2025Article
- Protofibril Binding Peptides Recognize and Inhibit Huntingtin Amyloid FormationbioRxiv : the preprint server for biology · 2025Article
- Transient Interdomain Interactions Modulate the Monomeric Structural Ensemble and Self-Assembly of Huntingtin Exon 1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Regulation of misfolded protein aggregation and degradation by SUMOylation in budding yeast.Molecular biology of the cell · 2025Article
- Direct Observation of Secondary Nucleation in Huntingtin Amyloid Formation by High-Speed Atomic Force Microscopy.Journal of the American Chemical Society · 2025Article
- Multiscale simulations elucidate the mechanism of polyglutamine aggregation and the role of flanking domains in fibril polymorphism.bioRxiv : the preprint server for biology · 2025Article
- Challenges and advances for huntingtin detection in cerebrospinal fluid: in support of relative quantification.Biomarker research · 2025Article
- Engineering a membrane protein chaperone to ameliorate the proteotoxicity of mutant huntingtin.Nature communications · 2025Article
- CCT and Cullin1 Regulate the TORC1 Pathway to Promote Dendritic Arborization in Health and Disease.Cells · 2024Article
- BDNF and TRiC-inspired reagent rescue cortical synaptic deficits in a mouse model of Huntington's disease.Neurobiology of disease · 2024Article
- Solid-state nuclear magnetic resonance in the structural study of polyglutamine aggregation.Biochemical Society transactions · 2024Review
- The N17 domain of huntingtin as a multifaceted player in Huntington's disease.Frontiers in molecular biosciences · 2024Review
- Fluorescent protein tagging promotes phase separation and alters the aggregation pathway of huntingtin exon-1.The Journal of biological chemistry · 2024Article
- The structure of pathogenic huntingtin exon 1 defines the bases of its aggregation propensity.Nature structural & molecular biology · 2023Article
- Early-Stage Oligomerization of Prion-like Polypeptides Reveals the Molecular Mechanism of Amyloid-Disrupting Capacity by Proline Residues.The journal of physical chemistry. B · 2023Article
- Neurodegenerative disease-associated inclusion bodies are cleared by selective autophagy in budding yeast.Autophagy reports · 2023Article
- The sequence context in poly-alanine regions: structure, function and conservation.Bioinformatics (Oxford, England) · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Many neurodegenerative diseases are linked to amyloid aggregation. In Huntington's disease (HD), neurotoxicity correlates with an increased aggregation propensity of a polyglutamine (polyQ) expansion in exon 1 of mutant huntingtin protein (mHtt). Here we establish how the domains flanking the polyQ tract shape the mHtt conformational landscape in vitro and in neurons. In vitro, the flanking domains have opposing effects on the conformation and stabilities of oligomers and amyloid fibrils. The N-terminal N17 promotes amyloid fibril formation, while the C-terminal Proline Rich Domain destabilizes fibrils and enhances oligomer formation. However, in neurons both domains act synergistically to engage protective chaperone and degradation pathways promoting mHtt proteostasis. Surprisingly, when proteotoxicity was assessed in rat corticostriatal brain slices, either flanking region alone sufficed to generate a neurotoxic conformation, while the polyQ tract alone exhibited minimal toxicity. Linking mHtt structural properties to its neuronal proteostasis should inform new strategies for neuroprotection in polyQ-expansion diseases.
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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.