| 1 | Peptides 2003 Jan 24: 137-46 |
|---|---|
| PMID | 12576095 |
| 标题 | PLG regulates hnRNP-L expression in the rat striatum and pre-frontal cortex: identification by ddPCR. |
| 抽象的 | Central dopaminergic systems are implicated inschizophreniaand Parkinson's disease, and are known to be modulated by the endogenous tripeptide Pro-Leu-Gly-NH(2) (PLG orMIF-1, melanocyte-stimulating hormone release inhibiting factor-1). Differential display polymerase chain reaction (ddPCR) was utilized to identify genes that are regulated by protracted PLG treatment (20 mg/kg, i.p. for 28 days) in male Sprague-Dawley rats. A total of 2400 genes were screened and 3 down-regulated bands were identified in the PLG-treated samples. Sequencing analysis revealed a total of six unique cDNA species. One fragment possessed a high degree of homology with Mus musculus hnRNP-L (protein L) mRNA (GenBank #AB009392) (termed PRG1: PLG regulated gene 1). Elongation of the PRG1 cDNA, by RACE-PCR, provided an 835 bp sequence with 95% homology to AB009392 over a 743 bp span. Open reading frame analysis provided a putative amino acid sequence consistent with the identity of PRG1 as rat hnRNP-L. Northern hybridization experiments with PRG1 revealed a 2.3 kb mRNA species that was decreased by 65% in the PLG-treated tissue. Western blot analysis revealed significantly decreased hnRNP-L levels in the striatum and pre-frontal cortex (but not the nucleus accumbens) by 71 and 61%, respectively of PLG-treated animals. The identification of altered expression of hnRNP-L following PLG treatment provides insight into the long-term effects of PLG and may provide insight into its molecular mechanism of action. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 2 | Psychiatry Res 2006 Sep 144: 39-47 |
| PMID | 16916546 |
| 标题 | 调查疾病易感性d the negative correlation of schizophrenia and rheumatoid arthritis focusing on MIF and CD14 gene polymorphisms. |
| 抽象的 | schizophreniaand rheumatoid arthritis (RA) are both chronic diseases with an estimated genetic component of 60%. While RA is a well-known autoimmune inflammatory joint disease, recent data point to an active immune process also being involved inschizophrenia. Several studies confirmed the negative association betweenschizophreniaand RA, indicating genetic factors that predispose to the one disorder, while protecting from the other. Macrophage migration inhibitory factor (MIF) and the monocytes surface receptor CD14 are involved in the development and maintenance of chronic inflammation. We therefore investigated if the -G173C single nucleotide polymorphism (SNP) and the tetranucleotide repeat CATT (5 - 8) at position -794 of theMIFgene and the CD14 - C159T transition are candidates for genetic liability toschizophreniaand RA or could explain the negative association between them. In our study 157schizophrenicpatients, 119 patients suffering from RA, and 225 healthy individuals were genotyped. All subjects were Caucasians. The CD14- andMIF-genotypes were equally distributed in all three groups. From our results, we cannot confirm the hypothesis that the investigated genetic mutations within theMIFand/or the CD14 gene are involved in the aetiology of either disease or could explain the negative correlation ofschizophreniaand RA. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 3 | Psychiatry Res 2006 Sep 144: 39-47 |
| PMID | 16916546 |
| 标题 | 调查疾病易感性d the negative correlation of schizophrenia and rheumatoid arthritis focusing on MIF and CD14 gene polymorphisms. |
| 抽象的 | schizophreniaand rheumatoid arthritis (RA) are both chronic diseases with an estimated genetic component of 60%. While RA is a well-known autoimmune inflammatory joint disease, recent data point to an active immune process also being involved inschizophrenia. Several studies confirmed the negative association betweenschizophreniaand RA, indicating genetic factors that predispose to the one disorder, while protecting from the other. Macrophage migration inhibitory factor (MIF) and the monocytes surface receptor CD14 are involved in the development and maintenance of chronic inflammation. We therefore investigated if the -G173C single nucleotide polymorphism (SNP) and the tetranucleotide repeat CATT (5 - 8) at position -794 of theMIFgene and the CD14 - C159T transition are candidates for genetic liability toschizophreniaand RA or could explain the negative association between them. In our study 157schizophrenicpatients, 119 patients suffering from RA, and 225 healthy individuals were genotyped. All subjects were Caucasians. The CD14- andMIF-genotypes were equally distributed in all three groups. From our results, we cannot confirm the hypothesis that the investigated genetic mutations within theMIFand/or the CD14 gene are involved in the aetiology of either disease or could explain the negative correlation ofschizophreniaand RA. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 4 | Peptides 2013 Apr 42: 89-96 |
| PMID | 23416534 |
| 标题 | MIF-1肽型，PAOPA的临床前药代动力学和毒理学评估：检查选择性多巴胺D2受体变构调节剂的药理学，用于治疗精神分裂症。 |
| 抽象的 | schizophreniais a mental illness characterized by a breakdown in cognition and emotion. Over the years, drug treatment for this disorder has mainly been compromised of orthosteric ligands that antagonize the active site of the dopamine D2 receptor. However, these drugs are limited in their use and often lead to the development of adverse movement and metabolic side effects. Allosteric modulators are an emerging class of therapeutics with significant advantages over orthosteric ligands, including an improved therapeutic and safety profile. This study investigates our newly developed allosteric modulator, PAOPA, which is a specific modulator of the dopamine D2 receptor. Previous studies have shown PAOPA to attenuateschizophrenia- 临床前模型中的行为异常。为了将这种新开发的变构药从临床前阶段促进临床阶段，这项研究研究了PAOPA的药代动力学行为和毒理学特征。这项研究的结果证明了Paopa在达到大脑的含义区域对治疗作用（尤其是纹状体）方面的有效性。发现PAOPA的药代动力学参数与当前市场抗精神病药相当。尸检和组织病理学分析均未显示所有检查器官的异常。PAOPA的急性和慢性治疗表明，使用当前典型的抗精神病药，没有通常发现运动异常。此外，急性和慢性PAOPA治疗表明，没有使用非典型抗精神病药物经典发现的血液学或代谢异常。这项研究的结果表明，PAOPA的安全性更好，并且需要这种新开发的治疗方法的进展schizophrenia. |
| SCZ关键字 | 精神分裂症，精神分裂症 |