ArticleThe Journal of clinical investigation2011
Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 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.
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Who cites it
111 citing papers in PubMed, 175 citations in OpenAlex.
- Transcriptional responses to proteotoxic stressors are profoundly diverse and tissue-specific.Cell stress & chaperones · 2026Article
- Heat Therapy: Targeting Health, Disease, and Disability.Comprehensive Physiology · 2026Review
- A small-molecule HSP90 inhibitor, NVP-HSP990, alleviates rotavirus infection.Journal of virology · 2026Article
- In Vivo Visualization and Quantification of Brain Heat Shock Protein 90 with [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Reversal of cognitive deficits in FUSNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- A clinical study and future prospects for bioactive compounds and semi-synthetic molecules in the therapies for Huntington's disease.Molecular neurobiology · 2024Review
- Deregulated Transcriptome as a Platform for Adrenal Huntington's Disease-Related Pathology.International journal of molecular sciences · 2024Article
- Preserved VPS13A distribution and expression in Huntington's disease: divergent mechanisms of action for similar movement disorders?Frontiers in neuroscience · 2024Article
- Heat shock factor HSF1 regulates BDNF gene promoters upon acute stress in the hippocampus, together with pCREB.Journal of neurochemistry · 2023Article
- Tumor suppressor p53 regulates heat shock factor 1 protein degradation in Huntington's disease.Cell reports · 2023Article
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- Protein Kinase CK2 and Its Potential Role as a Therapeutic Target in Huntington's Disease.Biomedicines · 2022Review
- Mitochondrial HSF1 triggers mitochondrial dysfunction and neurodegeneration in Huntington's disease.EMBO molecular medicine · 2022Article
- Is there a role for HSF1 in viral infections?FEBS open bio · 2022Review
- Divergent regulatory roles of NuRD chromatin remodeling complex subunits GATAD2 and CHD4 in Caenorhabditis elegans.Genetics · 2022Article
- The Intestine as a Lifespan- and Proteostasis-Promoting Signaling Tissue.Frontiers in aging · 2022Review
- TRAP1 in Oxidative Stress and Neurodegeneration.Antioxidants (Basel, Switzerland) · 2021Review
- Withaferin A Induces Heat Shock Response and Ameliorates Disease Progression in a Mouse Model of Huntington's Disease.Molecular neurobiology · 2021Article
- The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction.Scientific reports · 2021Article
- Combating deleterious phase transitions in neurodegenerative disease.Biochimica et biophysica acta. Molecular cell research · 2021Review
51 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Huntington disease (HD) is a devastating neurodegenerative disorder for which there are no disease-modifying treatments. Previous studies have proposed that activation of the heat shock response (HSR) via the transcription factor heat shock factor 1 (HSF1) may be of therapeutic benefit. However, the effect of disease progression on the HSR and the therapeutic potential of this pathway are currently unknown. Here, we used a brain-penetrating HSP90 inhibitor and physiological, molecular, and behavioral readouts to demonstrate that pharmacological activation of HSF1 improves huntingtin aggregate load, motor performance, and other HD-related phenotypes in the R6/2 mouse model of HD. However, the beneficial effects of this treatment were transient and diminished with disease progression. Molecular analyses to understand the transient nature of these effects revealed altered chromatin architecture, reduced HSF1 binding, and impaired HSR accompanied disease progression in both the R6/2 transgenic and HdhQ150 knockin mouse models of HD. Taken together, our findings reveal that the HSR, a major inducible regulator of protein homeostasis and longevity, is disrupted in HD. Consequently, pharmacological induction of HSF1 as a therapeutic approach to HD is more complex than was previously anticipated.
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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.