ArticleThe Journal of cell biology2016
Munc18-1 is a molecular chaperone for α-synuclein, controlling its self-replicating aggregation.
Article in The Journal of cell biology, 2016. 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 36 papers.
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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
36 citing papers in PubMed, 71 citations in OpenAlex.
- In vivo Proximity & Spatial Proteomics with CRISPR Screening Identify STXBP1 as a Protective Modifier of α-synuclein Toxicity in Dopamine Neurons.bioRxiv : the preprint server for biology · 2026Article
- Lysine myristoylation mediates long-term potentiation via membrane enrichment of synaptic plasticity effectors.The EMBO journal · 2025Article
- Exploring α-synuclein Interaction Partners and their Potential Clinical Implications for Parkinson's Disease.Neurochemical research · 2024Article
- Disease-linked mutations in Munc18-1 deplete synaptic Doc2.Brain : a journal of neurology · 2024Article
- GABAergic/Glycinergic and Glutamatergic Neurons Mediate Distinct Neurodevelopmental Phenotypes ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids.The EMBO journal · 2024Article
- Functional analysis of epilepsy-linked pathogenic variants of the Munc18-1 gene in the inhibitory nervous system ofmicroPublication biology · 2024Article
- Super-resolved trajectory-derived nanoclustering analysis using spatiotemporal indexing.Nature communications · 2023Article
- Fyn nanoclustering requires switching to an open conformation and is enhanced by FTLD-Tau biomolecular condensates.Molecular psychiatry · 2023Article
- Functional and Pathological Effects of α-Synuclein on Synaptic SNARE Complexes.Journal of molecular biology · 2023Review
- Mutation in thePediatric reports · 2022Article
- NOS1AP Interacts with α-Synuclein and Aggregates in Yeast and Mammalian Cells.International journal of molecular sciences · 2022Article
- Natural History Study of STXBP1-Developmental and Epileptic Encephalopathy Into Adulthood.Neurology · 2022Observational
- Clinical whole exome sequencing revealedSaudi journal of biological sciences · 2022Article
- Ferritinophagy and α-Synuclein: Pharmacological Targeting of Autophagy to Restore Iron Regulation in Parkinson's Disease.International journal of molecular sciences · 2022Review
- Transcriptome and Proteome Analysis in LUHMES Cells Overexpressing Alpha-Synuclein.Frontiers in neurology · 2022Article
- The role of the endolysosomal pathway in α-synuclein pathogenesis in Parkinson's disease.Frontiers in cellular neuroscience · 2022Review
- Article
- PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates.EMBO reports · 2021Article
- STXBP1 encephalopathies: Clinical spectrum, disease mechanisms, and therapeutic strategies.Journal of neurochemistry · 2021Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Munc18-1 is a key component of the exocytic machinery that controls neurotransmitter release. Munc18-1 heterozygous mutations cause developmental defects and epileptic phenotypes, including infantile epileptic encephalopathy (EIEE), suggestive of a gain of pathological function. Here, we used single-molecule analysis, gene-edited cells, and neurons to demonstrate that Munc18-1 EIEE-causing mutants form large polymers that coaggregate wild-type Munc18-1 in vitro and in cells. Surprisingly, Munc18-1 EIEE mutants also form Lewy body-like structures that contain α-synuclein (α-Syn). We reveal that Munc18-1 binds α-Syn, and its EIEE mutants coaggregate α-Syn. Likewise, removal of endogenous Munc18-1 increases the aggregative propensity of α-Syn(WT) and that of the Parkinson's disease-causing α-Syn(A30P) mutant, an effect rescued by Munc18-1(WT) expression, indicative of chaperone activity. Coexpression of the α-Syn(A30P) mutant with Munc18-1 reduced the number of α-Syn(A30P) aggregates. Munc18-1 mutations and haploinsufficiency may therefore trigger a pathogenic gain of function through both the corruption of native Munc18-1 and a perturbed chaperone activity for α-Syn leading to aggregation-induced neurodegeneration.
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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.