ArticlePloS one2008
Riluzole increases the amount of latent HSF1 for an amplified heat shock response and cytoprotection.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- A review of the neural mechanisms of action and clinical efficiency of riluzole in treating amyotrophic lateral sclerosis: what have we learned in the last decade?CNS neuroscience & therapeutics · 2011Pooled it
- EP300 confers protection against acute pancreatitis via acetylating HSF1 and promoting PRKN-mediated mitophagy in pancreatic acinar cells.Cell communication and signaling : CCS · 2025Article
- Riluzole is associated with reduced risk of heart failure.European journal of neurology · 2025Article
- The ALS-associated co-chaperone DNAJC7 mediates neuroprotection against proteotoxic stress by modulating HSF1 activity.bioRxiv : the preprint server for biology · 2024Article
- Article
- Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos.Neural regeneration research · 2023Article
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- Closest horizons of Hsp70 engagement to manage neurodegeneration.Frontiers in molecular neuroscience · 2023Review
- Riluzole partially restores RNA polymerase III complex assembly in cells expressing the leukodystrophy-causative variant POLR3B R103H.Molecular brain · 2022Article
- Is there a role for HSF1 in viral infections?FEBS open bio · 2022Review
- The interplay between oxidative stress and autophagy: focus on the development of neurological diseases.Behavioral and brain functions : BBF · 2022Review
- The Effects of Riluzole on Cisplatin-induced Ototoxicity.International archives of otorhinolaryngology · 2019Article
- Acetylation-induced TDP-43 pathology is suppressed by an HSF1-dependent chaperone program.Nature communications · 2017Article
- Neuroprotective Effect of Osthole on Neuron Synapses in an Alzheimer's Disease Cell Model via Upregulation of MicroRNA-9.Journal of molecular neuroscience : MN · 2016Article
- Elevation of serum heat-shock protein levels in amyotrophic lateral sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2016Article
- Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion.Frontiers in pharmacology · 2016Article
- Osthole confers neuroprotection against cortical stab wound injury and attenuates secondary brain injury.Journal of neuroinflammation · 2015Article
- Heat shock response and autophagy--cooperation and control.Autophagy · 2015Review
- Heat shock factor 1 over-expression protects against exposure of hydrophobic residues on mutant SOD1 and early mortality in a mouse model of amyotrophic lateral sclerosis.Molecular neurodegeneration · 2013Article
- Protein quality control system in neurodegeneration: a healing company hard to beat but failure is fatal.Molecular neurobiology · 2013Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInduction of the heat shock response (HSR) and increased expression of the heat shock proteins (HSPs) provide mechanisms to ensure proper protein folding, trafficking, and disposition. The importance of HSPs is underscored by the understanding that protein mis-folding and aggregation contribute centrally to the pathogenesis of neurodegenerative diseases. METHODOLOGY/PRINCIPAL
findingsWe used a cell-based hsp70-luciferease reporter gene assay system to identify agents that modulate the HSR and show here that clinically relevant concentrations of the FDA-approved ALS drug riluzole significantly increased the heat shock induction of hsp70-luciferse reporter gene. Immuno-Western and -cytochemical analysis of HSF1 show that riluzole increased the amount of cytosolic HSF1 to afford a greater activation of HSF1 upon heat shock. The increased HSF1 contributed centrally to the cytoprotective activity of riluzole as hsf1 gene knockout negated the synergistic activity of riluzole and conditioning heat shock to confer cell survival under oxidative stress. Evidence of a post-transcriptional mechanism for the increase in HSF1 include: quantitation of mRNA(hsf1) by RT-PCR showed no effect of either heat shock or riluzole treatment; riluzole also increased the expression of HSF1 from a CMV-promoter; analysis of the turnover of HSF1 by pulse chase and immunoprecipitation show that riluzole slowed the decay of [(35)S]labeled-HSF1. The effect of riluzole on HSF1 was qualitatively different from that of MG132 and chloroquine, inhibitors of the proteasome and lysosome, respectively, and appeared to involve the chaperone-mediated autophagy pathway as RNAi-mediated knockdown of CMA negated its effect. CONCLUSION/SIGNIFICANCE: We show that riluzole increased the amount of HSF1 to amplify the HSR for cytoprotection. Our study provides novel insight into the mechanism that regulates HSF1 turnover, and identifies the degradation of HSF1 as a target for therapeutics intervention.
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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.