ArticleNature neuroscience2015
The human epilepsy mutation GABRG2(Q390X) causes chronic subunit accumulation and neurodegeneration.
Article in Nature neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 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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Who cites it
78 citing papers in PubMed, 98 citations in OpenAlex.
- GABASynapse (New York, N.Y.) · 2026Review
- Potential Role of Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) Abnormalities in Epileptogenesis: Multimodal Mechanisms and Therapeutic Targets.Molecular neurobiology · 2026Review
- 4-Phenylbutyrate Rescue inCells · 2026Article
- Artificial intelligence in the assessment of epilepsy-related genetic mutations: Learned from GABAEpilepsia open · 2026Review
- 4-Phenylbutyrate Rescue inbioRxiv : the preprint server for biology · 2026Article
- Unraveling 4-Phenylbutyrate's Therapeutic Role in SLC6A1 Disorders: Pharmacochaperoning Over HDAC Inhibition.Annals of clinical and translational neurology · 2026Article
- Diverse species of animal models in epilepsy research: Progress and perspectives.Zoological research · 2025Review
- Beyond Impaired GABAergic Signaling: Inflammation and Metabolic Dysfunction in Genetic Epilepsy Induced by GABRG2 Mutation.Molecular neurobiology · 2025Article
- Preoptic area influences sleep-related seizures in a genetic epilepsy mouse model.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- Proteostasis regulation of GABABiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- Neuronal autophagy controls excitability via ryanodine receptor-mediated regulation of calcium-activated potassium channel function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Endoplasmic reticulum protein retention and disturbed proteostasis is a common pathology for a subset of autism: evidence from mutations in GABAFrontiers in molecular neuroscience · 2025Review
- GABRG2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics.Journal of translational medicine · 2024Review
- 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
- Identification of common core ion channel genes in epilepsy and Alzheimer's disease.Irish journal of medical science · 2024Review
- Article
- Established and emerging GABAFrontiers in pharmacology · 2024Review
- γ-Aminobutyric acid transporter and GABABrain communications · 2024Article
- Epilepsy plus blindness in microdeletion of GABRA1 and GABRG2 in mouse and human.Experimental neurology · 2023Article
- Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Genetic epilepsy and neurodegenerative diseases are two common neurological disorders that are conventionally viewed as being unrelated. A subset of patients with severe genetic epilepsies who have impaired development and often go on to die of their disease respond poorly to anticonvulsant drug therapy, suggesting a need for new therapeutic targets. Previously, we reported that multiple GABAA receptor epilepsy mutations result in protein misfolding and abnormal receptor trafficking. We have now developed a model of a severe human genetic epileptic encephalopathy, the Gabrg2(+/Q390X) knock-in mouse. We found that, in addition to impairing inhibitory neurotransmission, mutant GABAA receptor γ2(Q390X) subunits accumulated and aggregated intracellularly, activated caspase 3 and caused widespread, age-dependent neurodegeneration. These findings suggest that the fundamental protein metabolism and cellular consequences of the epilepsy-associated mutant γ2(Q390X) ion channel subunit are not fundamentally different from those associated with neurodegeneration. Our results have far-reaching relevance for the identification of conserved pathological cascades and mechanism-based therapies that are shared between genetic epilepsies and neurodegenerative diseases.
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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.