| http://purl.uniprot.org/citations/25485908 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25485908 | http://www.w3.org/2000/01/rdf-schema#comment | "Epilepsy is one of the most common and intractable brain disorders. Mutations in the human gene LGI1, encoding a neuronal secreted protein, cause autosomal dominant lateral temporal lobe epilepsy (ADLTE). However, the pathogenic mechanisms of LGI1 mutations remain unclear. We classified 22 reported LGI1 missense mutations as either secretion defective or secretion competent, and we generated and analyzed two mouse models of ADLTE encoding mutant proteins representative of the two groups. The secretion-defective LGI1(E383A) protein was recognized by the ER quality-control machinery and prematurely degraded, whereas the secretable LGI1(S473L) protein abnormally dimerized and was selectively defective in binding to one of its receptors, ADAM22. Both mutations caused a loss of function, compromising intracellular trafficking or ligand activity of LGI1 and converging on reduced synaptic LGI1-ADAM22 interaction. A chemical corrector, 4-phenylbutyrate (4PBA), restored LGI1(E383A) folding and binding to ADAM22 and ameliorated the increased seizure susceptibility of the LGI1(E383A) model mice. This study establishes LGI1-related epilepsy as a conformational disease and suggests new therapeutic options for human epilepsy."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.org/dc/terms/identifier | "doi:10.1038/nm.3759"xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Miyazaki T."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Ohkawa T."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Watanabe M."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Takahashi N."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Mochizuki Y."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Imoto K."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Fukata M."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Fukata Y."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Yokoi N."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Meijer D."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Hamakubo T."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Iwanari H."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Jaegle M."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/author | "Kase D."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/name | "Nat Med"xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/pages | "19-26"xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/title | "Chemical corrector treatment ameliorates increased seizure susceptibility in a mouse model of familial epilepsy."xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://purl.uniprot.org/core/volume | "21"xsd:string |
| http://purl.uniprot.org/citations/25485908 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25485908 |
| http://purl.uniprot.org/citations/25485908 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25485908 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JE04-mappedCitation-25485908 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25485908 |