ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
HSF1 protects neurons through a novel trimerization- and HSP-independent mechanism.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Involvement of heat shock proteins HSP70 in the mechanisms of endogenous neuroprotection: the prospect of using HSP70 modulators.Frontiers in cellular neuroscience · 2023Pooled it
- Review
- The Rapid Activation of MYDGF Is Critical for Cell Survival in the Acute Phase of Retinal Regeneration in Fish.International journal of molecular sciences · 2025Article
- HSPBiomedicines · 2025Article
- Glycogen synthase is required for heat shock-mediated autophagy induction in neuronal cells.Biology open · 2025Article
- The role of heat shock protein 70 on oocyte apoptosis during vitrification.Open veterinary journal · 2025Review
- HDAC6 modulates the cognitive behavioral function and hippocampal tissue pathological changes of APP/PS1 transgenic mice through HSP90-HSF1 pathway.Experimental brain research · 2024Article
- Disrupted HSF1 regulation in normal and exceptional brain aging.Biogerontology · 2024Article
- Kainic Acid-Induced Excitotoxicity Leads to the Activation of Heat Shock Response.Molecular neurobiology · 2023Article
- Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos.Neural regeneration research · 2023Article
- Closest horizons of Hsp70 engagement to manage neurodegeneration.Frontiers in molecular neuroscience · 2023Review
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- Quantitative Comparison of HSF1 Activators.Molecular biotechnology · 2022Article
- HSF1 is involved in suppressing A1 phenotype conversion of astrocytes following spinal cord injury in rats.Journal of neuroinflammation · 2021Article
- Review
- Bardoxolone Methyl Ameliorates Hyperglycemia Induced Mitochondrial Dysfunction by Activating the keap1-Nrf2-ARE Pathway in Experimental Diabetic Neuropathy.Molecular neurobiology · 2020Article
- Correction of Niemann-Pick type C1 trafficking and activity with the histone deacetylase inhibitor valproic acid.The Journal of biological chemistry · 2020Article
- The Bdnf and Npas4 genes are targets of HDAC3-mediated transcriptional repression.BMC neuroscience · 2019Article
- Catalytic-independent neuroprotection by SIRT1 is mediated through interaction with HDAC1.PloS one · 2019Article
- Neuroprotection by Heat Shock Factor-1 (HSF1) and Trimerization-Deficient Mutant Identifies Novel Alterations in Gene Expression.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Heat shock factor 1 (HSF1) protects neurons from death caused by the accumulation of misfolded proteins. It is believed that this protective effect is mediated by the transcriptional stimulation of genes encoding heat shock proteins (HSPs), a family of chaperones that refold or degrade misfolded proteins. Whether HSF1 is protective when neuronal death is not caused by protein misfolding has not been studied. Here, we report that HSF1 expression is necessary for the survival of rat neurons and that HSF1 mRNA and protein expression is reduced in neurons primed to die. Knock-down of HSF1 induces death of otherwise healthy neurons, whereas reestablishment of elevated levels of HSF1 protects neurons even when death is not due to accumulation of misfolded proteins. Neuroprotection by HSF1 does not require its trimerization, an event obligatory for the binding of HSF1 to heat shock elements within HSP gene promoters. Moreover, knock-down of HSP70 or blockade of HSP90 signaling does not reduce neuroprotection by HSF1. Although several neuroprotective molecules and signaling pathways, including CaMK, PKA, Casein kinase-II, and the Raf-MEK-ERK and PI-3K-Akt pathways, are not required for HSF1-mediated neuroprotection, protection is abrogated by inhibition of classical histone deacetylases (HDACs). We report that the novel mechanism of neuroprotection by HSF1 involves cooperation with SIRT1, an HDAC with well documented neuroprotective effects. Using a cell culture model of Huntington's disease, we show that HSF1 trimerization is not required for protection against mutant huntingtin-induced neurotoxicity, suggesting that HSF1 can protect neurons against both proteinopathic and nonproteinopathic death through a noncanonical pathway.
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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.