ArticleMolecular psychiatry2017
A CNS-permeable Hsp90 inhibitor rescues synaptic dysfunction and memory loss in APP-overexpressing Alzheimer's mouse model via an HSF1-mediated mechanism.
Article in Molecular psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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
37 citing papers in PubMed, 60 citations in OpenAlex.
- Pyrazole-derived TRPC3 antagonist ameliorates synaptic dysfunctions and memory deficits in Alzheimer's disease models.Molecular psychiatry · 2026Article
- Adaptive inter-tissue proteostasis networks in aging and neurodegeneration.Bioscience reports · 2026Review
- Beyond Inhibition: Rebalancing the Hsp90 Chaperone Network as a Therapeutic Strategy for Alzheimer's Disease.Drug design, development and therapy · 2026Review
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- In vivo imaging of heat shock protein 90: Diagnostic tool and support for Hsp90-targeted therapy.Cell stress & chaperones · 2025Review
- Soluble β-Amyloid Oligomers Selectively Upregulate TRPC3 in Excitatory Neurons via Calcineurin-Coupled NFAT.Cells · 2025Article
- In Vivo Visualization and Quantification of Brain Heat Shock Protein 90 with [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Decoding the role of large heat shock proteins in the progression of neuroinflammation-mediated neurodegenerative disorders.Neuroprotection (Chichester, England) · 2025Review
- Discovery of a potent and selective TRPC3 antagonist with neuroprotective effects.Bioorganic & medicinal chemistry · 2025Article
- The role of the FKBP51-Hsp90 complex in Alzheimer's disease: An emerging new drug target.Cell stress & chaperones · 2024Review
- Molecular Docking, Bioinformatic Analysis, and Experimental Verification for the Effect of Naringin on ADHD: Possible Inhibition of GSK-3β and HSP90.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Heat shock factor HSF1 regulates BDNF gene promoters upon acute stress in the hippocampus, together with pCREB.Journal of neurochemistry · 2023Article
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- Proteinopathies: Deciphering Physiology and Mechanisms to Develop Effective Therapies for Neurodegenerative Diseases.Molecular neurobiology · 2022Review
- Network Theoretical Approach to Explore Factors Affecting Signal Propagation and Stability in Dementia's Protein-Protein Interaction Network.Biomolecules · 2022Article
- The role and therapeutic potential of Hsp90, Hsp70, and smaller heat shock proteins in peripheral and central neuropathies.Medicinal research reviews · 2021Review
- Gut Inflammation Induced by Dextran Sulfate Sodium Exacerbates Amyloid-β Plaque Deposition in the AppNL-G-F Mouse Model of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2021Article
- Comprehensive Review on Alzheimer's Disease: Causes and Treatment.Molecules (Basel, Switzerland) · 2020Review
- Therapeutic Strategies to Reduce the Toxicity of Misfolded Protein Oligomers.International journal of molecular sciences · 2020Review
- Increased levels of Stress-inducible phosphoprotein-1 accelerates amyloid-β deposition in a mouse model of Alzheimer's disease.Acta neuropathologica communications · 2020Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
Abstract
Induction of neuroprotective heat-shock proteins via pharmacological Hsp90 inhibitors is currently being investigated as a potential treatment for neurodegenerative diseases. Two major hurdles for therapeutic use of Hsp90 inhibitors are systemic toxicity and limited central nervous system permeability. We demonstrate here that chronic treatment with a proprietary Hsp90 inhibitor compound (OS47720) not only elicits a heat-shock-like response but also offers synaptic protection in symptomatic Tg2576 mice, a model of Alzheimer's disease, without noticeable systemic toxicity. Despite a short half-life of OS47720 in mouse brain, a single intraperitoneal injection induces rapid and long-lasting (>3 days) nuclear activation of the heat-shock factor, HSF1. Mechanistic study indicates that the remedial effects of OS47720 depend upon HSF1 activation and the subsequent HSF1-mediated transcriptional events on synaptic genes. Taken together, this work reveals a novel role of HSF1 in synaptic function and memory, which likely occurs through modulation of the synaptic transcriptome.
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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.