ArticleNature communications2018
Mechanism-based rescue of Munc18-1 dysfunction in varied encephalopathies by chemical chaperones.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04937062 (Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy), which is not on this map. Cited by 53 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.
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.
Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
Who cites it
53 citing papers in PubMed, 84 citations in OpenAlex.
- NMN Ameliorates STXBP1-R292C Variant-mediated Developmental and Motor Dysfunction: Molecular Docking and Functional Studies.Journal of molecular neuroscience : MN · 2026Article
- Associations of Cortical and Subcortical White Matter Morphometric Abnormalities With Clinical and Genetic Findings inNeurology. Genetics · 2026Article
- STXBP1 Variants Associated With Epilepsy With Variable Severity.CNS neuroscience & therapeutics · 2026Article
- 4-Phenylbutyrate Rescue inCells · 2026Article
- Impaired Activity-Regulated Proteostasis: A Shared Mechanism in Neurodevelopmental Disorders.Biological psychiatry · 2026Review
- Virtual Screening and Zebrafish Phenotype-Based Evaluation Argues Against Repurposing 4-Phenylbutyrate for STXBP1-Related Disorders.Pharmacology research & perspectives · 2026Article
- Artificial intelligence in the assessment of epilepsy-related genetic mutations: Learned from GABAEpilepsia open · 2026Review
- Virtual screening and zebrafish phenotype-based evaluation argues against repurposing 4-phenylbutyrate for STXBP1-related disorders.bioRxiv : the preprint server for biology · 2026Article
- STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational Research.Biotech (Basel (Switzerland)) · 2025Review
- Disease-linked mutations in Munc18-1 deplete synaptic Doc2.Brain : a journal of neurology · 2024Article
- Reduced synaptic depression in human neurons carrying homozygous disease-causing STXBP1 variant L446F.Human molecular genetics · 2024Article
- Modulating Endoplasmic Reticulum Chaperones and Mutant Protein Degradation in GABRG2(Q390X) Associated with Genetic Epilepsy with Febrile Seizures Plus and Dravet Syndrome.International journal of molecular sciences · 2024Article
- GABAergic/Glycinergic and Glutamatergic Neurons Mediate Distinct Neurodevelopmental Phenotypes ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Article
- Genetic Advancements in Infantile Epileptic Spasms Syndrome and Opportunities for Precision Medicine.Genes · 2024Review
- The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids.The EMBO journal · 2024Article
- Article
- Functional analysis of epilepsy-linked pathogenic variants of the Munc18-1 gene in the inhibitory nervous system ofmicroPublication biology · 2024Article
- Reduced MUNC18-1 Levels, Synaptic Proteome Changes, and Altered Network Activity inBiological psychiatry global open science · 2024Article
- Microcircuit failure in STXBP1 encephalopathy leads to hyperexcitability.Cell reports. Medicine · 2023Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Heterozygous de novo mutations in the neuronal protein Munc18-1 are linked to epilepsies, intellectual disability, movement disorders, and neurodegeneration. These devastating diseases have a poor prognosis and no known cure, due to lack of understanding of the underlying disease mechanism. To determine how mutations in Munc18-1 cause disease, we use newly generated S. cerevisiae strains, C. elegans models, and conditional Munc18-1 knockout mouse neurons expressing wild-type or mutant Munc18-1, as well as in vitro studies. We find that at least five disease-linked missense mutations of Munc18-1 result in destabilization and aggregation of the mutant protein. Aggregates of mutant Munc18-1 incorporate wild-type Munc18-1, depleting functional Munc18-1 levels beyond hemizygous levels. We demonstrate that the three chemical chaperones 4-phenylbutyrate, sorbitol, and trehalose reverse the deficits caused by mutations in Munc18-1 in vitro and in vivo in multiple models, offering a novel strategy for the treatment of varied encephalopathies.
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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.