COOLING BATH -10
- Known as:
- COOLING BATH -10
- Catalog number:
- TBC-25
- Category:
- -
- Supplier:
- SBS
- Gene target:
- COOLING BATH -10
Related genes to: COOLING BATH -10
- 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: COOLING BATH -10
Related articles to: COOLING BATH -10
- Disease variants in genes encoding γ-Aminobutyric acid type A receptor (GABA R) subunits are major causes of developmental and epileptic encephalopathies (DEEs). There is no effective treatment for these DEEs although the GABA R is a major target for antiseizure drugs. We previously identified the therapeutic effect of 4-phenyl-butyrate (PBA) in knockin DEE mice and now test the effect of the drug in variants that encode the α1 subunit. We used a multidisciplinary approach including structural modeling, flow cytometry, patch clamp recordings and bio-chemistry in conjunction with differential tagging of the wild-type and the mutant alleles to evaluate the effect of PBA on rescue of GABA R subunit expression, surface trafficking, and function in heterologous HEK293T cell model and in mice. We found that both total and cell surface α1 expression was reduced when the variant α1 protein was present; suggesting reduced functional receptor on the cell membrane and synapse. Patch clamp recordings identified α1 variants reduced GABA-evoked current amplitude. prediction indicated reduced protein stability for variants indicated by negative ΔΔG values. PBA increased both total and surface expression of wildtype α1 and α1 variants; and improved expression of both wildtype and variant α1 alleles when these were co-expressed. Importantly, PBA also increased the GABA R expression in the 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 wildtype allele, repairing the mutant allele, and reducing endoplasmic reticulum stress. Therefore, 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: 2026/05/22
Song Ziang DebbieZavalin KirillShen WangzhenDeLeeuw Melissa BHunn Genevieve XEda Ria SMa LiCarson RobertKang Jing-Qiong - Caffeine (CAF) is a widely consumed psychostimulant known to modulate adenosine receptors and neurotransmitter systems, although its effects in invertebrates remain poorly understood. Environmentally relevant concentrations (5, 30, and 50 µg/L) are associated with altered behavior, including locomotion, exploration, and feeding, in the freshwater gastropod . This study examined molecular responses underlying these effects. Adult snails were exposed to CAF for 24 h and 7 days. Gene expression related to the nervous system and stress pathways was analyzed by RT-PCR, including , , , , , , , , , and . After 24 h, exposure to 50 µg/L CAF altered expression and caused downregulation of , , and , associated with observed behavioral changes. upregulation may indicate compensatory adjustment in adenosine signaling. After 7 days, remained upregulated, while genes linked to inhibitory neurotransmission showed partial recovery. Increased expression of genes involved in dopamine regulation and steroid metabolism suggested physiological adaptation. Overall, CAF induced dose- and time-dependent molecular responses in , linking neurochemical disruption with behavioral changes and highlighting its ecological risk as an emerging freshwater contaminant. - Source: PubMed
Publication date: 2026/05/20
Mohamed-Benhamu Ahlam - Solute carrier family 6 member 1 (SLC6A1) gene encodes gamma-aminobutyric acid transporter 1 (GAT-1), the principal synaptic gamma-aminobutyric acid (GABA) transporter. Pathogenic heterozygous loss-of-function variants of SLC6A1 cause a developmental and epileptic encephalopathy characterized by early-onset epilepsy, intellectual disability, and autistic features. Despite a rapidly expanding translational pipeline, clinical evidence remains fragmented. This scoping review systematically maps the published evidence on the phenotypic spectrum and therapeutic landscape of SLC6A1-related neurodevelopmental disorder. - Source: PubMed
Publication date: 2026/05/05
Samanta Debopam - Variants in SLC6A1, encoding the GABA transporter 1 (GAT-1), cause epilepsy, autism spectrum disorder, and developmental delay via loss of GABA uptake, impaired trafficking, and ER retention. We previously found that 4-Phenylbutyrate (PBA), an FDA-approved drug, restores GABA uptake and reduces seizures in SLC6A1-related disorders, prompting a phase I clinical trial (NCT04937062) primarily designed to evaluate safety and tolerability of Ravicti (PBA). However, its exact mechanism, pharmacochaperoning or histone deacetylase (HDAC) inhibition, remains unclear. This study compares PBA with pharmacochaperones and HDAC inhibitors to determine how it restores GAT-1 function in the cell and mouse models. - Source: PubMed
Publication date: 2026/05/19
DeLeeuw Melissa BRandhave KarishmaAnand EktaDebbie Song ZiangShen WangzhenKang Jing-Qiong - Early pregnancy loss (EPL), particularly when recurrent, represents a profoundly distressing experience for affected couples. Although chromosomal abnormalities are the most common cause of EPL, a substantial proportion of cases, especially those involving euploid embryos, remain unexplained. In this study, we investigated the potential contribution of rare monogenic variants to euploid EPL using whole-exome sequencing (WES). WES was performed on 66 euploid products of conceptions (POCs) from EPLs occurring before 12 gestational weeks. A molecular diagnosis with a high level of confidence, defined as the presence of pathogenic or likely pathogenic (P/LP) variant(s) consistent with the expected mode of inheritance, was established in 13/66 POCs (19.7%). These included one large 21q22.12-q22.3 duplication encompassing and . P/LP small variants were detected in , , , , , , , , and , representing genes with variable degrees of prior association with developmental phenotypes and, in some cases, limited or no evidence for embryonic lethality. In an additional 9/66 POCs (13.6%), findings were suggestive but not conclusive for a monogenic contribution. These included four cases with compound heterozygosity involving a pathogenic variant and a variant of uncertain significance (VUS) in autosomal recessive genes (, , , and ), as well as five cases harboring single heterozygous VUS in autosomal dominant genes (, , , , and ). The pathogenic relevance of these variants remains uncertain, particularly in the absence of functional validation. The implicated genes were clustered in biological categories: 1) genes plausibly associated with prenatal or early embryonic lethality, 2) genes causing severe congenital disorders not typically considered embryonically lethal, and 3) genes linked to later-onset or susceptibility phenotypes. These observations are consistent with a spectrum model in which highly deleterious variants may act as primary drivers of embryonic demise, whereas variants with reduced penetrance, later-onset associations or uncertain significance may contribute in a multifactorial context, potentially interacting with additional genetic, maternal or environmental factors. In conclusion, our findings suggest that monogenic variants may contribute to a subset of euploid EPL cases, although the strength of evidence varies considerably across detected variants. The integration of WES into the evaluation of recurrent euploid pregnancy loss holds promise but should be interpreted with caution. Further studies incorporating functional analyses, larger cohorts, and parental data are needed to clarify causality and to define the clinical utility of such approaches in genetic counseling, recurrence-risk assessment, and reproductive planning. - Source: PubMed
Publication date: 2026/05/14
Bozhinovski GjNoveski PTerzikj MKubelka-Sabit KPlaseska-Karanfilska D