| 1 | Pharmacol。Rev. 2003年9月55日：509-50 |
|---|---|
| PMID | 12869660 |
| 标题 | Molecular mechanisms and therapeutical implications of intramembrane receptor/receptor interactions among heptahelical receptors with examples from the striatopallidal GABA neurons. |
| 抽象的 | The molecular basis for the known intramembrane receptor/receptor interactions among G protein-coupled receptors was postulated to be heteromerization based on receptor subtype-specific interactions between different types of receptor homomers. The discovery of GABAB heterodimers started this field rapidly followed by the discovery of heteromerization among isoreceptors of several G protein-coupled receptors such as delta/kappa opioid receptors. Heteromerization was also discovered among distinct types of G protein-coupled receptors with the initial demonstration of somatostatinSSTR5/dopamine D2 and adenosine A1/dopamine D1 heteromeric receptor complexes. The functional meaning of these heteromeric complexes is to achieve direct or indirect (via adapter proteins) intramembrane receptor/receptor interactions in the complex. G protein-coupled receptors also form heteromeric complexes involving direct interactions with ion channel receptors, the best example being the GABAA/dopamine D5 receptor heteromerization, as well as with receptor tyrosine kinases and with receptor activity modulating proteins. As an example, adenosine, dopamine, and glutamate metabotropic receptor/receptor interactions in the striatopallidal GABA neurons are discussed as well as their relevance for Parkinson's disease,schizophrenia和药物依赖。异二聚体仅是一种杂体复合物，证据与高阶杂体复合物的存在同样兼容，在该复合物的存在中，辅助蛋白（如荷马蛋白和脚手架蛋白）也可以存在。这些复合物可能有助于将G蛋白偶联受体和离子通道受体连接到受体镶嵌物中，该过程可能具有特殊的整合价值，并且可能构成某些形式的学习和记忆形式的分子基础。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 2 | J Psychiatr Res 2010 Oct 44: 971-8 |
| PMID | 20398908 |
| 标题 | 精神疾病中神经元途径基因基因的综合拷贝数变体（CNV）分析确定了患者内部的罕见变异。 |
| 抽象的 | Copy number variations (CNV) have become an important source of human genome variability noteworthy to consider when studying genetic susceptibility to complex diseases. As recent studies have found evidences for the potential involvement of CNVs in psychiatric disorders, we have studied the dosage effect of structural genome variants as a possible susceptibility factor for different psychiatric disorders in a candidate gene approach. 在选择了68种精神疾病候选基因与CNV重叠后，MLPA分析旨在确定这些基因拷贝数的变化。研究样本由724例精神疾病患者组成（焦虑症，情绪障碍，饮食失调和schizophrenia）和341个对照个体。 CNVs were detected in 30 out of the 68 genes screened, indicating that a considerable proportion of neuronal pathways genes contain CNVs. When testing the overall burden of rare structural genomic variants in the different psychiatric disorders compared to control individuals, there was no statistically significant difference in the total amount of gains and losses. However, 14 out of the 30 changes were only found in psychiatric disorder patients but not in control individuals. These genes include GRM7, previously associated to major depression disorder and bipolar disorder, SLC6A13, in anxiety disorders, and S100B,SSTR5和COMT的schizophrenia. Although we have not been able to found a clear association between the studied CNVs and psychiatric disorders, the rare variants found only within the patients could account for a step further towards understanding the pathophysiology of psychiatric disorders. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 3 | 摩尔。精神病学2010年10月15日：1023-33 |
| PMID | 19528963 |
| 标题 | Association of common copy number variants at the glutathione S-transferase genes and rare novel genomic changes with schizophrenia. |
| 抽象的 | Copy number variants (CNVs) are a substantial source of human genetic diversity, influencing the variable susceptibility to multifactorial disorders.schizophreniais a complex illness thought to be caused by a number of genetic and environmental effects, few of which have been clearly defined. Recent reports have found several low prevalent CNVs associated with the disease. We have used a multiplex ligation-dependent probe amplification-based (MLPA) method to target 140 previously reported and putatively relevant gene-containing CNV regions in 654schizophrenic病人和604个对照组for association studies. Most genotyped CNVs (95%) showed very low (<1%) population frequency. A few novel rare variants were only present in patients suggesting a possible pathogenic involvement, including 1.39?Mb overlapping duplications at 22q11.23 found in two unrelated patients, and duplications of the somatostatin receptor 5 gene (SSTR5) at 16p13.3 in three unrelated patients. Furthermore, among the few relatively common CNVs observed in patients and controls, the combined analysis of gene copy number genotypes at two glutathione S-transferase (GST) genes, GSTM1 (glutathione S-transferase mu 1) (1p13.3) and GSTT2 (glutathione S-transferase theta 2) (22q11.23), showed a statistically significant association of non-null genotypes at both loci with an additive effect for increased vulnerability toschizophrenia(odds ratio of 1.92; P=0.0008). Our data provide complementary evidences for low prevalent, but highly penetrant chromosomal variants associated withschizophrenia，以及可能通过干扰谷胱甘肽代谢而充当易感因素的常见CNV。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 4 | 摩尔。精神病学2010年10月15日：1023-33 |
| PMID | 19528963 |
| 标题 | Association of common copy number variants at the glutathione S-transferase genes and rare novel genomic changes with schizophrenia. |
| 抽象的 | Copy number variants (CNVs) are a substantial source of human genetic diversity, influencing the variable susceptibility to multifactorial disorders.schizophreniais a complex illness thought to be caused by a number of genetic and environmental effects, few of which have been clearly defined. Recent reports have found several low prevalent CNVs associated with the disease. We have used a multiplex ligation-dependent probe amplification-based (MLPA) method to target 140 previously reported and putatively relevant gene-containing CNV regions in 654schizophrenic病人和604个对照组for association studies. Most genotyped CNVs (95%) showed very low (<1%) population frequency. A few novel rare variants were only present in patients suggesting a possible pathogenic involvement, including 1.39?Mb overlapping duplications at 22q11.23 found in two unrelated patients, and duplications of the somatostatin receptor 5 gene (SSTR5) at 16p13.3 in three unrelated patients. Furthermore, among the few relatively common CNVs observed in patients and controls, the combined analysis of gene copy number genotypes at two glutathione S-transferase (GST) genes, GSTM1 (glutathione S-transferase mu 1) (1p13.3) and GSTT2 (glutathione S-transferase theta 2) (22q11.23), showed a statistically significant association of non-null genotypes at both loci with an additive effect for increased vulnerability toschizophrenia(odds ratio of 1.92; P=0.0008). Our data provide complementary evidences for low prevalent, but highly penetrant chromosomal variants associated withschizophrenia，以及可能通过干扰谷胱甘肽代谢而充当易感因素的常见CNV。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |