ArticleBrain : a journal of neurology2022
Expression of 4E-BP1 in juvenile mice alleviates mTOR-induced neuronal dysfunction and epilepsy.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE): genetics, mechanisms and precision therapy.Acta neuropathologica · 2026Review
- Neuroinflammation in Epilepsy: Biochemical and Molecular Mechanisms and Implications for Natural Product-Driven Drug Discovery.International journal of molecular sciences · 2026Review
- Research progress on the relationship between long QT syndrome (LQTS) and epilepsy: A review.Medicine · 2026Review
- Metabolic dysregulation reshapes the immune landscape: The gut microbiota-mTOR axis in respiratory viral infection immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Decorin Attenuates Epileptogenesis and Modulates Hippocampal Synaptic Plasticity via the mTOR Signalling Pathway.Neurochemical research · 2026Article
- The 4E-BPs as Translational Regulators in Neurological Disorders: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2025Review
- Ablation of dysmorphic neurons is a safe and effective treatment for focal cortical dysplasia II.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Adiponectin targets the AMPK/mTOR signaling pathway to alleviate cognitive impairment in epilepsy.Molecular medicine reports · 2025Article
- Increased translation in adult mouse striatum is sufficient to induce motor dysfunction.Brain communications · 2025Article
- Reducing Filamin A Restores Cortical Synaptic Connectivity and Early Social Communication Following Cellular Mosaicism in Autism Spectrum Disorder Pathways.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Hyperactivity of mTORC1- and mTORC2-dependent signaling mediates epilepsy downstream of somatic PTEN loss.eLife · 2024Article
- The mTOR pathway geneseLife · 2024Article
- PI3K-AKT/mTOR Signaling in Psychiatric Disorders: A Valuable Target to Stimulate or Suppress?The international journal of neuropsychopharmacology · 2024Review
- Hyperactivity of mTORC1 and mTORC2-dependent signaling mediate epilepsy downstream of somatic PTEN loss.bioRxiv : the preprint server for biology · 2024Article
- The mTOR pathway genesbioRxiv : the preprint server for biology · 2024Article
- Advances in the mTOR signaling pathway and its inhibitor rapamycin in epilepsy.Brain and behavior · 2023Review
- mTORC2 Inhibition Improves Morphological Effects of PTEN Loss, But Does Not Correct Synaptic Dysfunction or Prevent Seizures.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- 4E-BP1 expression in embryonic postmitotic neurons mitigates mTORC1-induced cortical malformations and behavioral seizure severity but does not prevent epilepsy in mice.Frontiers in neuroscience · 2023Article
- Genetic mosaicism in the human brain: from lineage tracing to neuropsychiatric disorders.Nature reviews. Neuroscience · 2022Review
- The Coordination of mTOR Signaling and Non-Coding RNA in Regulating Epileptic Neuroinflammation.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Hyperactivation of the mTOR pathway during foetal neurodevelopment alters neuron structure and function, leading to focal malformation of cortical development and intractable epilepsy. Recent evidence suggests a role for dysregulated cap-dependent translation downstream of mTOR signalling in the formation of focal malformation of cortical development and seizures. However, it is unknown whether modifying translation once the developmental pathologies are established can reverse neuronal abnormalities and seizures. Addressing these issues is crucial with regards to therapeutics because these neurodevelopmental disorders are predominantly diagnosed during childhood, when patients present with symptoms. Here, we report increased phosphorylation of the mTOR effector and translational repressor, 4E-BP1, in patient focal malformation of cortical development tissue and in a mouse model of focal malformation of cortical development. Using temporally regulated conditional gene expression systems, we found that expression of a constitutively active form of 4E-BP1 that resists phosphorylation by focal malformation of cortical development in juvenile mice reduced neuronal cytomegaly and corrected several neuronal electrophysiological alterations, including depolarized resting membrane potential, irregular firing pattern and aberrant expression of HCN4 ion channels. Further, 4E-BP1 expression in juvenile focal malformation of cortical development mice after epilepsy onset resulted in improved cortical spectral activity and decreased spontaneous seizure frequency in adults. Overall, our study uncovered a remarkable plasticity of the juvenile brain that facilitates novel therapeutic opportunities to treat focal malformation of cortical development-related epilepsy during childhood with potentially long-lasting effects in adults.
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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 Socratic graph.