GABRG2 Peptide
- Known as:
- GABRG2 Peptide
- Catalog number:
- 42-570P
- Product Quantity:
- 0.1 mg
- Category:
- -
- Supplier:
- Prosci
- Gene target:
- GABRG2 Peptide
Related genes to: GABRG2 Peptide
- Gene:
- GABRG2 NIH gene
- Name:
- gamma-aminobutyric acid type A receptor gamma2 subunit
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 5q34
- Locus Type:
- gene with protein product
- Date approved:
- 1991-02-26
- Date modifiied:
- 2016-02-04
Related products to: GABRG2 Peptide
Related articles to: GABRG2 Peptide
- A significant number of patients with genetic epilepsy do not obtain seizure freedom, despite developments in new antiseizure drugs, suggesting a need for novel therapeutic approaches. Many genetic epilepsies are associated with misfolded mutant proteins, including -associated Dravet syndrome, which we have previously shown to result in intracellular accumulation of mutant GABA receptor γ2(Q390X) subunit protein. Thus, a potentially promising therapeutic approach is modulation of proteostasis, such as increasing endoplasmic reticulum (ER)-associated degradation (ERAD). To that end, we have here identified an ERAD-associated E3 ubiquitin ligase, HRD1, among other ubiquitin ligases, as a strong modulator of wildtype and mutant γ2 subunit expression. Overexpressing HRD1 or knockdown of HRD1 dose-dependently reduced the γ2(Q390X) subunit. Additionally, we show that zonisamide (ZNS)-an antiseizure drug reported to upregulate HRD1-reduces seizures in the mouse. We propose that a possible mechanism for this effect is a partial rescue of surface trafficking of GABA receptors, which are otherwise sequestered in the ER due to the dominant-negative effect of the γ2(Q390X) subunit. Furthermore, this partial rescue was not due to changes in ER chaperones BiP and calnexin, as total expression of these chaperones was unchanged in γ2(Q390X) models. Our results here suggest that leveraging the endogenous ERAD pathway may present a potential method to degrade neurotoxic mutant proteins like the γ2(Q390X) subunit. We also demonstrate a pharmacological means of regulating proteostasis, as ZNS alters protein trafficking, providing further support for the use of proteostasis regulators for the treatment of genetic epilepsies. - Source: PubMed
Publication date: 2024/04/23
Poliquin SarahNwosu GeraldRandhave KarishmaShen WangzhenFlamm CarsonKang Jing-Qiong - Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy syndrome characterized by seizures that predominantly occur during sleep. The pathogenesis of these seizures remains unclear. We previously detected rare variants in GABRG2, which encodes the γ subunit of γ-aminobutyric acid type A receptor (GABAR), in patients with SHE and demonstrated that these variants impaired GABAR function in vitro. However, the mechanisms by which GABRG2 variants contribute to seizure attacks during sleep remain unclear. - Source: PubMed
Publication date: 2024/04/09
Jiang Yong-LiXia LiangZhao Jing-JingZhou Hui-MinMi DanWang XuanWang Yuan-YuanSong Chang-GengJiang Wen - Rapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABA receptors. The gene, which encodes the α5 subunit of the GABA receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of pediatric brain tumor. However, the possible role of GABA receptor subunits in glioma remains poorly understood. Here, we examined the expression of genes encoding GABA receptor subunits in different types of glioma, and its possible association with patient prognosis assessed by overall survival (OS). Data were obtained from the French and The Cancer Genome Atlas Brain Lower Grade Glioma (TCGA-LGG) datasets and analyzed for expression of GABA receptor subunit genes. OS was calculated using the Kaplan-Meier estimate. We found that genes , , , , and showed a significant association with OS, with higher gene expression indicating better prognosis. In patients with GBM, high expression of was associated with shorter OS, whereas, in contrast, higher levels of were associated with better prognosis indicated by longer OS. In patients with lower grade gliomas, , , , and , were associated with longer OS. High expression was related to longer survival when low grade glioma types were analyzed separately. Our results suggest an overall association between higher expression of most genes encoding GABA receptor subunits and better prognosis in different types of glioma. Our findings support the possibility that down-regulation of GABA receptors in glioma contributes to promoting tumor progression by reducing negative inhibition. These findings might contribute to further evaluation of GABA receptors as a therapeutic target in glioma. - Source: PubMed
Publication date: 2024/03/14
Badalotti RafaelDalmolin MatheusMalafaia OsvaldoRibas Filho Jurandir MRoesler RafaelFernandes Marcelo A CIsolan Gustavo R - Absence seizures are characterized by brief lapses in awareness accompanied by a hallmark spike-and-wave discharge (SWD) electroencephalographic pattern and are common to genetic generalized epilepsies (GGEs). While numerous genes have been associated with increased risk, including some Mendelian forms with a single causal allele, most cases of GGE are idiopathic and there are many unknown genetic modifiers of GGE influencing risk and severity. In a previous meta-mapping study, crosses between transgenic C57BL/6 and C3HeB/FeJ strains, each carrying one of three SWD-causing mutations (Gabrg2 , Scn8a or Gria4 ), demonstrated an antagonistic epistatic interaction between loci on mouse chromosomes 2 and 7 influencing SWD. These results implicate universal modifiers in the B6 background that mitigate SWD severity through a common pathway, independent of the causal mutation. In this study, we prioritized candidate modifiers in these interacting loci. Our approach integrated human genome-wide association results with gene interaction networks and mouse brain gene expression to prioritize candidate genes and pathways driving variation in SWD outcomes. We considered candidate genes that are functionally associated with human GGE risk genes and genes with evidence for coding or non-coding allele effects between the B6 and C3H backgrounds. Our analyses output a summary ranking of gene pairs, one gene from each locus, as candidates for explaining the epistatic interaction. Our top-ranking gene pairs implicate microtubule function, cytoskeletal stability and cell cycle regulation as novel hypotheses about the source of SWD variation across strain backgrounds, which could clarify underlying mechanisms driving differences in GGE severity in humans. - Source: PubMed
Lara Montana KayBrabec Jeffrey LHernan Amanda EScott Rod CTyler Anna LMahoney J Matthew - To explore the mechanism involved in variable phenotypes of epilepsy models induced by γ-aminobutyric acid type A γ2 subunit (GABRG2) mutations. - Source: PubMed
Sui JiahuiZhan LongwuJi ShengtaoWu WenwenChen YuhanYun FengLiang WenpengWang JieCao MaohongShen DingdingZhang Qi