ArticleCell reports2022
DEPDC5-dependent mTORC1 signaling mechanisms are critical for the anti-seizure effects of acute fasting.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 21 citations in OpenAlex.
- Tuberous sclerosis complex.Nature reviews. Disease primers · 2026Review
- Dietary restriction as a potential neuroprotective intervention: a narrative review of its impact on neuroinflammation across neurodegenerative diseases and other neurological disorders.Frontiers in nutrition · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Focal DEPDC5 loss without disruption to cerebral cortical neuron migration recapitulates DEPDC5-related focal epilepsy.JCI insight · 2025Article
- Ancient genomic linkage of α-globin and Nprl3 couples metabolism with erythropoiesis.Nature communications · 2025Article
- Article
- Mechanistic target of rapamycin in regulating macrophage function in inflammatory cardiovascular diseases.Journal of molecular and cellular cardiology · 2024Review
- Intermittent fasting interventions to leverage metabolic and circadian mechanisms for cancer treatment and supportive care outcomes.Journal of the National Cancer Institute. Monographs · 2023Article
- The regulatory function of lncRNA and constructed network in epilepsy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Review
- Treatment-Resistant Epilepsy and Tuberous Sclerosis Complex: Treatment, Maintenance, and Future Directions.Neuropsychiatric disease and treatment · 2023Review
- Review
- Review
- Watch Out for GATORs: Fasting, Seizures, and Nutrient Sensing.Epilepsy currentsArticle
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Caloric restriction and acute fasting are known to reduce seizures but through unclear mechanisms. mTOR signaling has been suggested as a potential mechanism for seizure protection from fasting. We demonstrate that brain mTORC1 signaling is reduced after acute fasting of mice and that neuronal mTORC1 integrates GATOR1 complex-mediated amino acid and tuberous sclerosis complex (TSC)-mediated growth factor signaling. Neuronal mTORC1 is most sensitive to withdrawal of leucine, arginine, and glutamine, which are dependent on DEPDC5, a component of the GATOR1 complex. Metabolomic analysis reveals that Depdc5 neuronal-specific knockout mice are resistant to sensing significant fluctuations in brain amino acid levels after fasting. Depdc5 neuronal-specific knockout mice are resistant to the protective effects of fasting on seizures or seizure-induced death. These results establish that acute fasting reduces seizure susceptibility in a DEPDC5-dependent manner. Modulation of nutrients upstream of GATOR1 and mTORC1 could offer a rational therapeutic strategy for epilepsy treatment.
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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.