ArticleDisease models & mechanisms2012
The antiepileptic drug valproic acid and other medium-chain fatty acids acutely reduce phosphoinositide levels independently of inositol in Dictyostelium.
Article in Disease models & mechanisms, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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.
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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.
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Who cites it
38 citing papers in PubMed, 78 citations in OpenAlex.
- A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy.The British journal of nutrition · 2015Trial
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- Developing a Tanshinone IIA Memetic by Targeting MIOS to Regulate mTORC1 and Autophagy in Glioblastoma.International journal of molecular sciences · 2024Article
- Functional mechanism study of the allelochemical myrigalone A identifies a group of ultrapotent inhibitors of ethylene biosynthesis in plants.Plant communications · 2024Article
- Relationship between Dietary Decanoic Acid and Coronary Artery Disease: A Population-Based Cross-Sectional Study.Nutrients · 2023Article
- Medium-Chain Fatty Acids Rescue Motor Function and Neuromuscular Junction Degeneration in aCells · 2023Article
- Sustained release of valproic acid loaded on chitosan nanoparticles within hybrid of alginate/chitosan hydrogel with/without stem cells in regeneration of spinal cord injury.Progress in biomaterials · 2023Article
- Enhanced Sestrin expression through Tanshinone 2A treatment improves PI3K-dependent inhibition of glioma growth.Cell death discovery · 2023Article
- Structural basis of AMPA receptor inhibition by trans-4-butylcyclohexane carboxylic acid.British journal of pharmacology · 2022Article
- Review
- Editorial:Frontiers in cell and developmental biology · 2022Article
- Moving the Research Forward: The Best of British Biology Using the Tractable Model SystemCells · 2021Review
- Decanoic Acid Stimulates Autophagy inCells · 2021Article
- Phytocannabinoid-dependent mTORC1 regulation is dependent upon inositol polyphosphate multikinase activity.British journal of pharmacology · 2021Article
- UsingFrontiers in cell and developmental biology · 2021Review
- Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- ABiochemistry and biophysics reports · 2020Article
- A multicenter randomized controlled trial of medium-chain triglyceride dietary supplementation on epilepsy in dogs.Journal of veterinary internal medicine · 2020Article
- A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models.British journal of pharmacology · 2020Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Valproic acid (VPA) is the most widely prescribed epilepsy treatment worldwide, but its mechanism of action remains unclear. Our previous work identified a previously unknown effect of VPA in reducing phosphoinositide production in the simple model Dictyostelium followed by the transfer of data to a mammalian synaptic release model. In our current study, we show that the reduction in phosphoinositide [PtdInsP (also known as PIP) and PtdInsP(2) (also known as PIP(2))] production caused by VPA is acute and dose dependent, and that this effect occurs independently of phosphatidylinositol 3-kinase (PI3K) activity, inositol recycling and inositol synthesis. In characterising the structural requirements for this effect, we also identify a family of medium-chain fatty acids that show increased efficacy compared with VPA. Within the group of active compounds is a little-studied group previously associated with seizure control, and analysis of two of these compounds (nonanoic acid and 4-methyloctanoic acid) shows around a threefold enhanced potency compared with VPA for protection in an in vitro acute rat seizure model. Together, our data show that VPA and a newly identified group of medium-chain fatty acids reduce phosphoinositide levels independently of inositol regulation, and suggest the reinvestigation of these compounds as treatments for epilepsy.
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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 Socratic graph.