WATER BATH 5 LITRES 100
- Known as:
- WATER BATH 5 LITRES 100
- Catalog number:
- TBN-06/100
- Category:
- -
- Supplier:
- SBS
- Gene target:
- WATER BATH 5 LITRES 100
Related genes to: WATER BATH 5 LITRES 100
- Gene:
- SLC6A1 NIH gene
- Name:
- solute carrier family 6 member 1
- Previous symbol:
- -
- Synonyms:
- GAT1, GABATR, GABATHG
- Chromosome:
- 3p25.3
- Locus Type:
- gene with protein product
- Date approved:
- 1994-02-16
- Date modifiied:
- 2016-02-17
Related products to: WATER BATH 5 LITRES 100
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- Disease variants in genes encoding γ-aminobutyric acid type A receptor (GABAR) subunits are major causes of developmental and epileptic encephalopathies (DEEs). There is no effective treatment for these DEEs, although the GABAR is a major target for antiseizure drugs. We previously identified the therapeutic effect of 4-phenylbutyrate (PBA) in knockin DEE mice and in this study tested the effect of the drug in variants that encode the α1 subunit of GABAR. We used a multidisciplinary approach including in silico structural modeling, flow cytometry, patch-clamp recordings and biochemistry in conjunction with differential tagging of the wildtype (WT) and the mutant alleles to evaluate the effect of PBA on rescue of GABAR subunit expression, surface trafficking, and function in vitro in a heterologous HEK293T cell model and in vivo in mice. We found that the α1 subunit expression at both the total level and the cell surface was reduced when the variant α1 protein was present, suggesting reduced functional receptor availability on the cell membrane and synapse. Patch-clamp recordings identified that α1 variants reduced GABA-evoked current amplitude. In silico prediction indicated reduced protein stability for variants by negative ∆∆G values. PBA increased both total and surface expression of WT α1 and α1 variants and improved expression of both WT and variant α1 alleles when these were co-expressed. Importantly, PBA also increased the GABAR expression in the cortex and thalamus of the mice. This study indicates that PBA is a promising treatment option for DEEs associated with mutations. Our previous work has demonstrated that PBA improves proteostasis by enhancing expression of the WT allele, repairing the mutant allele, and reducing endoplasmic reticulum stress in other DEEs associated with and mutations. Importantly, it can mitigate seizures and improve neurobehavioral phenotypes at behavioral levels. Based on this and our previous work on and mutations, we propose that PBA holds promise as a common medicine for multiple genetic neurologic disorders that share the proteostasis pathology with a broad clinical application in DEEs. - Source: PubMed
Publication date: 2026/07/24
Song Ziang DebbieZavalin KirillShen WangzhenDeLeeuw Melissa BHunn Genevieve XEda Ria SMa LiWang JuexinKang Jing-Qiong - The primary control mechanism for synaptic uptake of GABA is through γ-aminobutyric acid transporter 1 (GAT-1, SLC6A1), a known target for anti-epileptic drugs. Although there is a clinically used GAT-1 inhibitor, tiagabine, the development of a new ligand with an advanced pharmacological profile is desirable. For this purpose, a multi-tiered virtual approach to screening has been created, involving pharmacophore-based search; application of the Informational Spectrum Method for Small Molecules, followed by EIIP/AQVN filtering (ISM-SM); molecular docking using an ensemble of several experimentally obtained structures of GAT-1; and ADMET predictions. Pharmacophore-based screening of the ZINC database of natural products, combined with ISM-SM/EIIP filtering, yielded 237 candidate compounds. Structural separation analysis discriminated between the positives and negatives, enabling enrichment-based prioritization. The use of a composite normalized rank score based on docking affinity and structural similarity allowed for the identification of the top candidates: ZINC03643214 and ZINC67840571. Collectively, these refinements establish a more sophisticated computational model for identifying novel GAT-1 inhibitors and highlight promising candidates for future experimental evaluation. - Source: PubMed
Publication date: 2026/06/29
Stevanovic KristinaPerovic VladimirGlisic SanjaSencanski Milan - The mechanistic effects of genetic variants underlying genetic neurodevelopmental disorders (NDDs) are widely studied, but the contribution of external factors remains largely unexplored. - Source: PubMed
Publication date: 2026/07/18
Boßelmann Christian MLudwig Natasha NHolingue CalliopeJimenez-Gomez AndresGanna AndreaPerry M ScottArenivas AnaLal Dennis - Preclinical studies and early clinical trials suggest phenylbutyrate (an FDA and European Medicines Agency-approved medication for urea cycle disorders) may improve seizure control in certain developmental and epileptic encephalopathies (DEEs). Its effect on development is unknown, and comorbidities like hypotonia may raise toxicity risks. This study examines early clinical experiences with phenylbutyrate in children with DEEs, outside the context of a clinical trial. - Source: PubMed
Publication date: 2026/06/20
Barbour KristenStӧdberg TommyLarsson AnnaDahlin MariaGrinspan Zachary M - Monogenic epilepsies are 1.6 times more likely to be treatment-resistant compared to other epilepsies, emphasizing the need for additional therapeutic strategies. Sleep dysfunction beyond sleep-related breathing disorders is common yet insufficiently characterized and treated in monogenic epilepsies. We therefore sought to study sleep phenotypes across these epilepsies, examine associations with seizure severity, and assess the diagnostic rate of sleep disorders. From 2,519 individuals enrolled in the Epilepsy Genetics Research Project at Children's Hospital of Philadelphia, we identified the monogenic epilepsies most frequently associated with sleep-related diagnoses, yielding 252 individuals across nine genetic diagnoses ( , 79; , 57; , 34; , 21; , 14; , 13; , 13; , 11; , 10). Monogenic epilepsies exhibited distinct sleep endophenotypes, including insomnia, parasomnia, and sleep-related movement disorders in -related disorders; frequent epileptiform discharges in sleep with insomnia symptoms in -related disorders; sleep dysfunction restricted to the developmental and epileptic encephalopathy subtype in -related disorders; and insomnia without nocturnal seizure involvement in -related disorders. Formal sleep diagnoses were present in only 25% of individuals (63/252), yet 58% (145/252) reported sleep difficulties, suggesting substantial underdiagnosis. Persistent seizures were associated with higher odds of sleep disorder diagnoses ( 2.87, 1.57-5.36), disrupted sleep architecture ( 2.06, 1.08-4.16), nocturnal seizures ( 4.47, 2.50-8.28), hypersomnolence ( 2.38, 1.27-4.58) and insomnia ( 1.80, 1.06-3.05). Neuropsychiatric comorbidities were independently associated with sleep burden after adjustment for seizure severity ( 2.49, 1.40-4.49). We find that monogenic epilepsies exhibit distinct, gene-specific sleep endophenotypes that are underdiagnosed. Treating sleep difficulties beyond obstructive sleep apnoea may improve seizure control and developmental outcomes, highlighting the need for timely diagnosis of co-occurring sleep disorders. - Source: PubMed
Publication date: 2026/06/29
Bochtler Katharina SBatterman Alexander IKoh Hyun YongKessler RileyEsparza ChristineShon JoyKaufman Michael CHelbig IngoCuddapah Vishnu Anand