ArticleNature neuroscience2014
Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates fear extinction memory.
Article in Nature neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 2 of them syntheses that pooled it.
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
127 citing papers in PubMed, 2 syntheses or guidelines pooled it, 214 citations in OpenAlex.
- Inflammation, Anti-inflammatory Interventions, and Post-stroke Cognitive Impairment: a Systematic Review and Meta-analysis of Human and Animal Studies.Translational stroke research · 2025Pooled it
- The efficacy and safety of fingolimod plus standardized treatment versus standardized treatment alone for acute ischemic stroke: A systematic review and meta-analysis.Pharmacology research & perspectives · 2022Pooled it
- Combination of the Immune Modulator Fingolimod With Alteplase in Acute Ischemic Stroke: A Pilot Trial.Circulation · 2015Trial
- Article
- Epigenetic Mechanisms Underlying Cognitive Dysfunction in Parkinson's Disease: Current Evidence and Future Prospects.Brain and behavior · 2026Review
- Lipid metabolism and neurodegeneration: Mechanistic insights and therapeutic targets.Ageing research reviews · 2026Review
- Fingolimod normalizes metabolic signatures associated with synaptic plasticity and memory in APP/PS1 model: Sphingosine-1-phosphate receptor a therapeutic target for Alzheimer's.Scientific reports · 2026Article
- Fingolimod Effects on Motor Function and BDNF-TrkB Signaling in a Huntington's Mouse Model Are Disease-Stage-Dependent.International journal of molecular sciences · 2026Article
- BRSK2 plays a role in autophagy and cancer cell growth and survival under nutrient deprivation stress via the PIK3C3 pathway.Scientific reports · 2025Article
- Inhibition of T cell infiltration and soluble TNF signaling is neuroprotective in the alpha-synuclein overexpressing mouse model of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Mechanisms of high-density lipoprotein in regulating blood-brain barrier function: insights and implications.Fluids and barriers of the CNS · 2025Review
- Fingolimod Improves Anxiety-like Behavior and Modulates Sphingosine-1-Phosphate Receptors Gene Expression in a Diabetic Mouse Model.Biomolecules · 2025Article
- PET Imaging of Sphingosine-1-Phosphate Receptor 1 with [Molecular imaging and biology · 2025Article
- Rescue of hippocampal synaptic plasticity and memory performance by Fingolimod (FTY720) in APP/PS1 model of Alzheimer's disease is accompanied by correction in metabolism of sphingolipids, polyamines, and phospholipid saturation composition.bioRxiv : the preprint server for biology · 2025Article
- Dissociation between the anti-allodynic effects of fingolimod (FTY720) and desensitization of S1PNeuropharmacology · 2024Article
- Brain region specific regulation of anandamide (down) and sphingosine-1-phosphate (up) in association with anxiety (AEA) and resilience (S1P) in a mouse model of chronic unpredictable mild stress.Pflugers Archiv : European journal of physiology · 2024Article
- Behavioral Analyses in Dark Agouti Rats Following Repeated Systemic Treatment With Fingolimod (FTY720).Brain and behavior · 2024Article
- Regulation of cellular and systemic sphingolipid homeostasis.Nature reviews. Molecular cell biology · 2024Review
- N-oleoyl alanine attenuates nicotine reward and spontaneous nicotine withdrawal in mice.Drug and alcohol dependence · 2024Article
- PET Imaging of Sphingosine-1-Phosphate Receptor 1 with [18F]TZ4877 in Nonhuman Primates.Research square · 2024Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
FTY720 (fingolimod), an FDA-approved drug for treatment of multiple sclerosis, has beneficial effects in the CNS that are not yet well understood, independent of its effects on immune cell trafficking. We show that FTY720 enters the nucleus, where it is phosphorylated by sphingosine kinase 2 (SphK2), and that nuclear FTY720-P binds and inhibits class I histone deacetylases (HDACs), enhancing specific histone acetylations. FTY720 is also phosphorylated in mice and accumulates in the brain, including the hippocampus, inhibits HDACs and enhances histone acetylation and gene expression programs associated with memory and learning, and rescues memory deficits independently of its immunosuppressive actions. Sphk2(-/-) mice have lower levels of hippocampal sphingosine-1-phosphate, an endogenous HDAC inhibitor, and reduced histone acetylation, and display deficits in spatial memory and impaired contextual fear extinction. Thus, sphingosine-1-phosphate and SphK2 play specific roles in memory functions and FTY720 may be a useful adjuvant therapy to facilitate extinction of aversive memories.
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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.