GNAO1 siRNA_Lentivectors
- Known as:
- GNAO1 siRNA_Lentivectors
- Catalog number:
- i008863d
- Product Quantity:
- 500ng
- Category:
- -
- Supplier:
- ABM
- Gene target:
- GNAO1 siRNA_Lentivectors
Related genes to: GNAO1 siRNA_Lentivectors
- Gene:
- GNAO1 NIH gene
- Name:
- G protein subunit alpha o1
- Previous symbol:
- -
- Synonyms:
- G-ALPHA-o
- Chromosome:
- 16q13
- Locus Type:
- gene with protein product
- Date approved:
- 1988-04-24
- Date modifiied:
- 2016-03-03
Related products to: GNAO1 siRNA_Lentivectors
Related articles to: GNAO1 siRNA_Lentivectors
- : Pathogenic variants in , encoding the inhibitory G protein subunit Gαo, cause severe neurodevelopmental disorders that remain largely refractory to pharmacological treatments. Gαo transduces inhibitory signals downstream of multiple G protein-coupled receptors (GPCRs) involved in motor control. Here, we used gene-edited models carrying variants, the ortholog of , to investigate GPCR contributions to Gαo-dependent locomotor phenotypes. : We combined pharmacological screening of dopamine- and cannabinoid-targeting ligands in mutants with structural analysis of ligand-binding pocket conservation and genetic perturbation of receptor function using RNAi and knockout approaches. : Pharmacological modulation of GPCR signaling produced non-linear and context-dependent effects. Compounds predicted to further increase excitability may instead promote phenotypic improvement, consistent with compensatory network rebalancing. Structural analyses revealed substantial divergence in ligand-binding pocket conservation for several GPCR-ligand pairs, suggesting that altered binding affinity and selectivity may also contribute to the observed phenotypic outcome. Pharmacological experiments performed in GPCR-depleted mutants allowed for the correlation of structural findings with functional effects for selected receptor-ligand pairs. Finally, genetic reduction in GPCRs coupled to stimulatory G proteins ameliorated hyperactive locomotion in mutants, whereas reduction in GPCRs coupled to inhibitory G proteins is largely insufficient to induce or exacerbate locomotor defects. : Our findings identify excessive excitatory GPCR input as a key modulator of motor dysfunction in the context of impaired Gαo signaling. They also show that structural conservation is a necessary but not sufficient condition to predict functional responses. Overall, this study establishes as a suitable platform to dissect GPCR-mediated signaling and highlights the value of integrating pharmacological and genetic approaches to guide target selection in -related disorders. - Source: PubMed
Publication date: 2026/05/18
Di Rocco MartinaDi Rienzo LorenzoFollo Francesca CarmenD'Alessandro ManuelaGalosi SerenaPannone LucaVenanzi SerenellaDi Schiavi EliaMartire AlbertoBessereau Jean-LouisLeuzzi VincenzoMilanetti EdoardoMartinelli Simone - Growth hormone (GH) stimulation tests have limited reliability and may lead to false-positive results. - Source: PubMed
Publication date: 2026/05/07
Plachy LukasDusatkova PetraKavciak LukasAmaratunga Shenali AnneSlavenko MatveiDrabova JanaMaratova KlaraNeuman VitObermannova BarboraKolouskova StanislavaSnajderova MartaSumnik ZdenekLebl JanPruhova Stepanka - GNAO1-related neurodevelopmental disorders are caused by mutations in the GNAO1 gene encoding the major neuronal G protein, Gαo. GNAO1 encephalopathies manifest in a range of symptoms, including epilepsy, movement disorder, hypotonia, and developmental delay, affecting >400 patients worldwide to date. A growth in the number of diagnosed cases is expected due to the wider availability of whole genome sequencing. One of the most recurrent pathogenic variants causing GNAO1 encephalopathy is an intronic mutation c.724-8G>A, which results in an in-frame insertion of two amino acid residues, Pro-Gln, after Thr241: Gαo[T241_N242insPQ]. We previously performed in-depth profiling of Gαo[insPQ] using structural, biochemical, and cellular studies. Compared with the wild-type protein, Gαo[insPQ] exhibits faster GTP binding and decreased hydrolysis. Importantly, Gαo[insPQ] is deficient in interacting with regulator of G protein signaling (RGS), GTPase-activating proteins that deactivate Gαo. These defects render Gαo[insPQ] a constitutively active mutant loaded with GTP in the G protein signaling. Patients harboring Gαo[insPQ] variant are in urgent need of novel therapy as they are refractory to available medications. In the present study, we performed a high-throughput screening to find molecules that might suppress the constitutive GTP loading by Gαo[insPQ]. We used a high-diversity chemical library of 54080 compounds, identifying a novel compound, N-[5-(2-methylpropyl)-1,3,4-thiadiazol-2-yl]-1H-1,2,3-benzotriazole-5-carboxamide, that decreases the GTP binding rate of Gαo, likely acting as a competitive inhibitor with higher selectivity to the pathogenic protein. This small-molecule inhibitor of Gαo opens new opportunities to drug discovery towards Gαo-dependent pathologies. - Source: PubMed
Larasati Yonika AKoval AlexeyKatanaev Vladimir L - Pathogenic variants in GNAO1 cause a spectrum of epilepsy, movement disorders, and developmental impairment. Clinical heterogeneity complicates prognosis and therapeutic development. We present the first longitudinal natural history study of GNAO1-related disorders (GNAO1-RD) to delineate phenotypic trajectories. - Source: PubMed
Publication date: 2026/04/17
Domínguez-Carral JanaDomínguez Cobo Ana MaríaBalsells SolAguilar-Ros AnnaChang Chu-TingLudlam William GYang KathrynBernardi KaterinaChinigioli MicaelaSalazar-Villacorta AinaraDi Pisa VeronicaLamagrande-Casanova NuriaGonzález-Alguacil ElenaDe la Casa-Fages BeatrizOkumura AkihisaRodríguez JosefinaAgarwal AyushMuñoz-Chesta DanielaReynoso-Osnayo CarolinaLin AmyTabarki BrahimParvin JobaidaGallo Adolfo AlbertoForno AndreiaMaass FabianMontiel Blanco JohnnyNasif SaloméJennions ElizabethRamón-Gómez Jorge LuisVerhelst HeleneNieto Barceló Juan JoséČokolić Petrović DunjaGarcía Ruiz Luz Victoriavan Riesen ChristophRego Sousa PauloMassaro Sanchez Maria Del PilarKhan Husnea AraHakami WejdanFriedman JenniferEspinoza-Quinteros IvánTroncoso MonicaGarg DivyaniPauni MicaelaKurahashi HirokazuMiranda-Herrero María ConcepciónDuat-Rodriguez AnnaSoliani LucaKurian Manju ASchteinschnaider AngelesSrivastava SiddharthEbrahimi-Fakhari DariusMartemyanov Kirill AOrtigoza-Escobar Juan Darío - Equine melanocytic neoplasms (EMN) are aggressive tumours characterised by high metastatic potential and limited therapeutic options available. However, the molecular mechanisms underlying their progression remain poorly understood. This study therefore presents the integrative phosphoproteomic analysis of EMN tissue, with the aim of elucidating stage-specific alterations in signalling pathways and metabolism. Nineteen tissue samples from grey horses were categorised as normal-stage (n = 6), early-stage EMN (n = 7), and severe-stage EMN (n = 6) and subjected to in-depth analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 2035 phosphoproteins were identified, of which 219 were differentially expressed across the disease stages. Interestingly, early-stage EMN showed dysregulation of inositol phosphate metabolism and activation of the PI3K-Akt pathway which involved INPP5F and PKN2. In severe-stage EMN, upregulation of SYNJ1, STRN4 and VIM indicated enhanced membrane trafficking, cytoskeletal remodelling, and MAPK signalling. Additionally, ASPM and GNAO1 upregulation reflected heightened proliferation and altered Rap1 signalling, while UBR5 dysregulation suggested aberrant protein homeostasis. Metabolic reprogramming was also noticed, with elevated TKT and GAPDH expression supporting glycolysis and NADPH production. Observably, the severe-stage EMN exhibited a higher expression of Dickkopf-3 (DKK3) which suggests a role in aberrant Wnt/β-catenin activation and tumour progression. These findings reveal stage-specific molecular mechanisms in EMN pathogenesis and highlight potential biomarkers and therapeutic targets for equine melanoma. - Source: PubMed
Publication date: 2026/04/16
Srimontri PaitoonKingkaw AmornthepPrapaiwan NawarusSujittosakul RangsimaIamkaewprasert NichapatPiputwat JiraschayaIsama-Al PuettaMunkongdee ThanutchanokChotikaprakal ThanaponYanyongsirikarn PetchpailinPhaonakrop NarumonRoytrakul SittirukVongsangnak WanwipaTesena Parichart