| 1 | Int. J. Neuropsychopharmacol. 2011 Feb 14: 1-15 |
|---|---|
| PMID | 20158934 |
| 标题 | 性别差异在信号路径的活动ways and expression of G-protein-coupled receptor kinases in the neonatal ventral hippocampal lesion model of schizophrenia. |
| 抽象的 | Animals with the neonatal ventral hippocampal lesion (NVHL) demonstrate altered responsiveness to stress and various drugs reminiscent of that inschizophrenia。Post-pubertal onset of abnormalities suggests the possibility of sex differences in NVHL effects that may model sex differences inschizophrenia。在这里，我们证明了雄性和雌性NVHL大鼠的新颖性和MK-801诱导的多动症是显而易见的，而仅NVHL雄性对阿哌汀的反应过度活跃。接下来，我们检查了ERK和AKT途径活性的性别和NVHL依赖性差异。在女性中，两种途径的基础活性都比男性高。NVHL降低了两性中ERK1/2，AKT和GSK-3的磷酸化水平，尽管男性表现出更加一致的下调。雌性具有较高水平的G蛋白偶联激酶[G蛋白偶联受体激酶（GRK）] 3和5，而其他GRK和抑制蛋白的浓度相同。在伏隔核中，浓度grk5in females was elevated by NVHL to the male level. The data demonstrate profound sex differences in the expression and activity of signalling molecules that may underlie differential susceptibility toschizophrenia。 |
| SCZ关键字 | schizophrenia |
| 2 | J. Biol. Chem. 2013 May 288: 15712-24 |
| PMID | 23592773 |
| 标题 | G蛋白受体激酶5调节大麻素受体2诱导的5-羟色胺2A受体的上调。 |
| 抽象的 | We have recently reported that cannabinoid agonists can up-regulate and enhance the activity of serotonin 2A (5-HT2A) receptors in the prefrontal cortex (PFCx). Increased expression and activity of cortical 5-HT2A receptors has been associated with neuropsychiatric disorders, such as anxiety andschizophrenia。Here we report that repeated CP55940 exposure selectively up-regulatesgrk5大鼠PFCX和神经元细胞培养模型中的蛋白质。我们试图检查调节的基础机制grk5and to identify the role ofgrk5in the cannabinoid agonist-induced up-regulation and enhanced activity of 5-HT2A receptors. Interestingly, we found that cannabinoid agonist-induced up-regulation ofgrk5involves CB2 receptors, ?-arrestin 2, and ERK1/2 signaling because treatment with CB2 shRNA lentiviral particles, ?-arrestin 2 shRNA lentiviral particles, or ERK1/2 inhibitor prevented the cannabinoid agonist-induced up-regulation ofgrk5。最重要的是，我们发现grk5shRNA lentiviral particle treatment prevented the cannabinoid agonist-induced up-regulation and enhanced 5-HT2A receptor-mediated calcium release. Repeated cannabinoid exposure was also associated with enhanced phosphorylation of CB2 receptors and increased interaction between ?-arrestin 2 and ERK1/2. These latter phenomena were also significantly inhibited bygrk5shRNA慢病毒治疗。我们的结果表明，上调5-HT2A受体信号的CB2受体的持续激活增强了grk5expression; the phosphorylation of CB2 receptors; and the ?-arrestin 2/ERK interactions. These data could provide a rationale for some of the adverse effects associated with repeated cannabinoid agonist exposure. |
| SCZ关键字 | schizophrenia |
| 3 | Schizophr. Res. 2014 Oct 159: 130-5 |
| PMID | 25153362 |
| 标题 | Increased G protein-coupled receptor kinase (GRK) expression in the anterior cingulate cortex in schizophrenia. |
| 抽象的 | Current pharmacological treatments forschizophreniatarget G protein-coupled receptors (GPCRs), including dopamine receptors. Ligand-bound GPCRs are regulated by a family of G protein-coupled receptor kinases (GRKs), members of which uncouple the receptor from heterotrimeric G proteins, desensitize the receptor, and induce receptor internalization via the arrestin family of scaffolding and signaling molecules. GRKs initiate the activation of downstream signaling pathways, can regulate receptors and signaling molecules independent of GPCR phosphorylation, and modulate epigenetic regulators like histone deacetylases (HDACs). We hypothesize that the expression of GRK proteins is altered inschizophrenia，与以前在促进细胞内信号传导过程的分子家族的变化的发现一致。 In this study, we measured protein expression via Western blot analysis for GRKs 2, 3, 5, and 6 in the anterior cingulate cortex of patients withschizophrenia（n = 36）和比较组（n = 33）。为了控制抗精神病药物治疗，我们在氟哌啶醇治疗的和未处理的大鼠中测量了这些相同的靶标（两者的n = 10）。 We found increased levels ofgrk5inschizophrenia。在用氟哌啶醇脱氧酸盐治疗的大鼠中，在GRK蛋白表达中未检测到变化9个月。 These data suggest that increasedgrk5expression may contribute to the pathophysiology ofschizophrenia通过异常调节细胞骨架，内吞作用，信号传导，GPCR和组蛋白修饰。 |
| SCZ关键字 | schizophrenia |
| 4 | Gene 2015 Nov 572: 175-83 |
| PMID | 26149656 |
| 标题 | Role of long purine stretches in controlling the expression of genes associated with neurological disorders. |
| 抽象的 | Purine repeat sequences present in the human genome are known to act as hotspots for mutations leading to chromosomal imbalances. It is established that large purine repeats (PRs) form stable DNA triplex structure which can inhibit gene expression. Friedreich's ataxia (FRDA), the autosomal neurodegenerative disorder is the only human disease known so far, where a large purine (GAA) repeat in the FXN gene is known to inhibit the expression of frataxin protein. We explored the hidden purine repeats (PRn with n ? 200) if any, in the human genome to find out how they are associated with neurological disorders. The results showed 28 PRs, which are mostly restricted to the intronic regions. Interestingly, the transcriptome expression analysis of PR-carrying genes (PR-genes) revealed that most of them are down-regulated in neurological disorders (autism, Alzheimer's disease,schizophrenia，与健康对照组相比，癫痫，智力低下，帕金森氏病，脑肿瘤）。可以用嘌呤重复的扩展来解释脑疾病中基因表达的改变，从而导致形成非常稳定的DNA-TRIPLEX和/或减轻修复酶和/或其他未知细胞因子。Interactome分析在信号通路中确定了四个PR生成，其失调与发病机理直接相关：grk5and KLK6 in Alzheimer's disease; FGF14 in craniosynostosis, mental retardation and FLT1 in neuroferritinopathy. By virtue of being mutational hotspots and their ability to form DNA-triplex, purine repeats in genome disturb the genome integrity and interfere with the transcriptional regulation. However, validation of the disease linkage of PR-genes can be validated using knock-out techniques. |
| SCZ关键字 | schizophrenia |