ArticlePLoS biology2010
Modulation of heat shock transcription factor 1 as a therapeutic target for small molecule intervention in neurodegenerative disease.
Article in PLoS biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
112 citing papers in PubMed, 189 citations in OpenAlex.
- Heat shock transcription factors in development and disease.Disease models & mechanisms · 2026Review
- Lack of MDA5 delays hematopoietic aging by modulating inflammaging and proteostasis in mice.Nature communications · 2026Article
- Celastrol Activates HSF1 to Enhance Regulatory T Cells Function and Ameliorate Intestinal Inflammation.Biomolecules · 2025Article
- The Hsf1-sHsp cascade has pan-antiviral activity in mosquito cells.Communications biology · 2025Article
- HSF1 Activation Mechanisms, Disease Roles, and Small Molecule Therapeutics.International journal of biological sciences · 2025Review
- Heat shock factor 1 drives regulatory T-cell induction to limit murine intestinal inflammation.Mucosal immunology · 2024Article
- Disrupted HSF1 regulation in normal and exceptional brain aging.Biogerontology · 2024Article
- The Chaperonin TRiC/CCT Inhibitor HSF1A Protects Cells from Intoxication with Pertussis Toxin.Toxins · 2024Article
- Modulating Stress Proteins in Response to Therapeutic Interventions for Parkinson's Disease.International journal of molecular sciences · 2023Review
- Optimal HSF1 activation in response to acute cold stress in BAT requires nuclear TXNIP.iScience · 2023Article
- Molecular Chaperones' Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis.Cells · 2023Review
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- The function and regulation of heat shock transcription factor inFrontiers in cellular and infection microbiology · 2023Review
- Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis by regulating the respiratory process.Nature communications · 2022Article
- Quantitative Comparison of HSF1 Activators.Molecular biotechnology · 2022Article
- Is there a role for HSF1 in viral infections?FEBS open bio · 2022Review
- Stress-responsive regulation of extracellular proteostasis.The Journal of cell biology · 2022Review
- Single-cell transcriptomics identifies Gadd45b as a regulator of herpesvirus-reactivating neurons.EMBO reports · 2022Article
- The TRiCky Business of Protein Folding in Health and Disease.Frontiers in cell and developmental biology · 2022Review
- HSF-1: Guardian of the Proteome Through Integration of Longevity Signals to the Proteostatic Network.Frontiers in aging · 2022Review
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Neurodegenerative diseases such as Huntington disease are devastating disorders with no therapeutic approaches to ameliorate the underlying protein misfolding defect inherent to poly-glutamine (polyQ) proteins. Given the mounting evidence that elevated levels of protein chaperones suppress polyQ protein misfolding, the master regulator of protein chaperone gene transcription, HSF1, is an attractive target for small molecule intervention. We describe a humanized yeast-based high-throughput screen to identify small molecule activators of human HSF1. This screen is insensitive to previously characterized activators of the heat shock response that have undesirable proteotoxic activity or that inhibit Hsp90, the central chaperone for cellular signaling and proliferation. A molecule identified in this screen, HSF1A, is structurally distinct from other characterized small molecule human HSF1 activators, activates HSF1 in mammalian and fly cells, elevates protein chaperone expression, ameliorates protein misfolding and cell death in polyQ-expressing neuronal precursor cells and protects against cytotoxicity in a fly model of polyQ-mediated neurodegeneration. In addition, we show that HSF1A interacts with components of the TRiC/CCT complex, suggesting a potentially novel regulatory role for this complex in modulating HSF1 activity. These studies describe a novel approach for the identification of new classes of pharmacological interventions for protein misfolding that underlies devastating neurodegenerative disease.
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What OpenQuestion holds
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.