ArticleThe Journal of biological chemistry2011
Neuroprotective drug riluzole amplifies the heat shock factor 1 (HSF1)- and glutamate transporter 1 (GLT1)-dependent cytoprotective mechanisms for neuronal survival.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 63 citations in OpenAlex.
- Beta-lactam Antibiotic Cefepime Attenuates Lipopolysaccharide-induced Pain and Depression By Modulating Inflammatory Response and Astroglial Glutamate Transporter in Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Troriluzole attenuates opioid intake, reinforcing efficacy, seeking behaviours, physical dependence and antinociceptive tolerance in rats.British journal of pharmacology · 2026Article
- Innovative Therapeutic Strategies Targeting the Network Architecture of Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Assessing the efficacy of amyotrophic lateral sclerosis drugs in slowing disease progression: A literature review.AIMS neuroscience · 2024Review
- Modeling disrupted synapse formation in wolfram syndrome using hESCs-derived neural cells and cerebral organoids identifies Riluzole as a therapeutic molecule.Molecular psychiatry · 2023Article
- A Medicinal Chemistry Perspective on Excitatory Amino Acid Transporter 2 Dysfunction in Neurodegenerative Diseases.Journal of medicinal chemistry · 2023Review
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- Troriluzole inhibits methamphetamine place preference in rats and normalizes methamphetamine-evoked glutamate carboxypeptidase II (GCPII) protein levels in the mesolimbic pathway.Drug and alcohol dependence · 2023Article
- High-fat diet induces depression-like phenotype via astrocyte-mediated hyperactivation of ventral hippocampal glutamatergic afferents to the nucleus accumbens.Molecular psychiatry · 2022Article
- Is there a role for HSF1 in viral infections?FEBS open bio · 2022Review
- Prionoids in amyotrophic lateral sclerosis.Brain communications · 2022Review
- Identification of HSF1 Target Genes Involved in Thermal Stress in the Pacific Oyster Crassostrea gigas by ChIP-seq.Marine biotechnology (New York, N.Y.) · 2020Article
- The Effects of Riluzole on Cisplatin-induced Ototoxicity.International archives of otorhinolaryngology · 2019Article
- Riluzole Impairs Cocaine Reinstatement and Restores Adaptations in Intrinsic Excitability and GLT-1 Expression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Riluzole: a potential therapeutic intervention in human brain tumor stem-like cells.Oncotarget · 2017Article
- Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse.The international journal of neuropsychopharmacology · 2017Review
- Astroglia as a cellular target for neuroprotection and treatment of neuro-psychiatric disorders.Glia · 2017Review
- Role of astrocytic glutamate transporter in alcohol use disorder.World journal of psychiatry · 2016Review
- NEDD4-mediated HSF1 degradation underlies α-synucleinopathy.Human molecular genetics · 2016Article
- Requirement for endogenous heat shock factor 1 in inducible nitric oxide synthase induction in murine microglia.Journal of neuroinflammation · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heat shock factor 1 (HSF1) mediates the cellular response to stress to increase the production of heat shock protein (HSP) chaperones for proper protein folding, trafficking, and degradation; failure of this homeostatic mechanism likely contributes to neurodegeneration. We show that the neuroprotective drug riluzole increased the amount of HSF1 in NG108-15 neuroprogenitor cells by slowing the specific turnover of HSF1 and supporting a more robust and sustained activation of HSF1. Using Hsp70-luciferase as a functional readout of the activity of HSF1, we show that riluzole amplified the heat shock induction of the reporter gene with an optimal increase at 1 μM. Immunocytochemical staining and Western blot quantitation of HSP70 in NG108-15 neuroprogenitor cells and embryonic spinal cord neurons provided corroborative evidence that riluzole amplified the HSF1-dependent regulation of HSP70 expression. Parallel studies on the GLT1 glutamate transporter showed that riluzole increased GLT1-reporter and GLT1 protein expression and that the increase was enhanced by heat shock and coincident with the increased expression of HSP70 and HSP90. This result is consistent with the anti-glutamatergic profile of riluzole and the presence of multiple heat shock elements on the GLT1 gene promoter, suggesting that riluzole may modulate GLT1 expression through HSF1. The increased HSP chaperones and GLT1 transporter blunted glutamate-induced and N-methyl D-aspartate receptor-mediated excitotoxic death. In summary, we show that riluzole increased the amount and activity of HSF1 to boost the expression of HSPs and GLT1 for neuroprotection under stress.
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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.