ArticleScientific reports2017
Polyglutamine expansion affects huntingtin conformation in multiple Huntington's disease models.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Development of aniScience · 2026Article
- Lipid Composition Drives Mutant Huntingtin Dimerization and Membrane Association: Insights from Computational Simulations.Molecules (Basel, Switzerland) · 2026Article
- Copper Homeostasis and Cuproptosis in Neurological Disorders.Drug design, development and therapy · 2026Review
- Neurodegeneration Through the Lens of Bioinformatics Approaches: Computational Mechanisms of Protein Misfolding.International journal of molecular sciences · 2025Review
- PI5P4K inhibitors: promising opportunities and challenges.The FEBS journal · 2025Review
- Advances in Huntington's Disease Biomarkers: A 10-Year Bibliometric Analysis and a Comprehensive Review.Biology · 2025Review
- Docosahexaenoic Acid (DHA) Supplementation in a Triglyceride Form Prevents from Polyglutamine-Induced Dysfunctions inInternational journal of molecular sciences · 2024Article
- Therapeutic approaches targeting aging and cellular senescence in Huntington's disease.CNS neuroscience & therapeutics · 2024Review
- 1953-2023. Seventy Years of the Nerve Growth Factor: A Potential Novel Treatment in Neurological Diseases?Aging and disease · 2024Review
- IKBKB reduces huntingtin aggregation by phosphorylating serine 13 via a non-canonical IKK pathway.Life science alliance · 2023Article
- Unravelling theMolecules (Basel, Switzerland) · 2022Article
- Article
- Chemical-Mediated Targeted Protein Degradation in Neurodegenerative Diseases.Life (Basel, Switzerland) · 2021Review
- Site-Specific Phosphorylation of Huntingtin Exon 1 Recombinant Proteins Enabled by the Discovery of Novel Kinases.Chembiochem : a European journal of chemical biology · 2021Article
- Analysis of mutant and total huntingtin expression in Huntington's disease murine models.Scientific reports · 2020Article
- TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models.The EMBO journal · 2020Article
- Protein Quantification and Imaging by Surface-Enhanced Raman Spectroscopy and Similarity Analysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Assessing average somatic CAG repeat instability at the protein level.Scientific reports · 2019Article
- Targeting the proteostasis network in Huntington's disease.Ageing research reviews · 2019Review
- N-terminal Huntingtin (Htt) phosphorylation is a molecular switch regulating Htt aggregation, helical conformation, internalization, and nuclear targeting.The Journal of biological chemistry · 2018Article
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Authors and funding
21 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Conformational changes in disease-associated or mutant proteins represent a key pathological aspect of Huntington's disease (HD) and other protein misfolding diseases. Using immunoassays and biophysical approaches, we and others have recently reported that polyglutamine expansion in purified or recombinantly expressed huntingtin (HTT) proteins affects their conformational properties in a manner dependent on both polyglutamine repeat length and temperature but independent of HTT protein fragment length. These findings are consistent with the HD mutation affecting structural aspects of the amino-terminal region of the protein, and support the concept that modulating mutant HTT conformation might provide novel therapeutic and diagnostic opportunities. We now report that the same conformational TR-FRET based immunoassay detects polyglutamine- and temperature-dependent changes on the endogenously expressed HTT protein in peripheral tissues and post-mortem HD brain tissue, as well as in tissues from HD animal models. We also find that these temperature- and polyglutamine-dependent conformational changes are sensitive to bona-fide phosphorylation on S13 and S16 within the N17 domain of HTT. These findings provide key clinical and preclinical relevance to the conformational immunoassay, and provide supportive evidence for its application in the development of therapeutics aimed at correcting the conformation of polyglutamine-expanded proteins as well as the pharmacodynamics readouts to monitor their efficacy in preclinical models and in HD patients.
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