| 1 | J. Clin。投资。2007年3月117日：672-82 |
|---|---|
| PMID | 17290303 |
| 标题 | Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition. |
| Abstract | Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32), encoded byPPP1R1B, is a pivotal integrator of information in dopaminoceptive neurons, regulating the response to neuroleptics, psychotomimetics, and drugs of abuse, and affecting striatal function and plasticity. Despite extensive preclinical work, there are almost no data on DARPP-32 function in humans. Here, we identify, through resequencing in 298 chromosomes, a frequentPPP1R1Bhaplotype predicting mRNA expression ofPPP1R1Bisoforms in postmortem human brain. This haplotype was associated with enhanced performance on several cognitive tests that depend on frontostriatal function. Multimodal imaging of healthy subjects revealed an impact of the haplotype on neostriatal volume, activation, and the functional connectivity of the prefrontal cortex. The haplotype was associated with the risk for精神分裂症在1个基于家庭的关联分析中。我们的收敛结果确定了受变化影响的前额叶神经系统PPP1R1B并建议DARPP-32在认知功能中起关键作用，并且可能在精神分裂症。 |
| SCZ关键字 | 精神分裂症, schizophrenic |
| 2 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2007 Aug 31: 1303-6 |
| PMID | 17618027 |
| 标题 | An association study between PPP1R1B gene and schizophrenia in the Chinese population. |
| Abstract | 精神分裂症与谷氨酸能，多巴胺能和血清素能神经传递的功能障碍有关。相对分子质量32 kDa（DARPP-32）的多巴胺和cAMP调节的磷蛋白，由编码PPP1R1B（蛋白质磷酸酶1，调节/抑制剂亚基1B）基因富含新纹状体培养基神经元。它在多巴胺能和谷氨酸能信号通路中起关键调节剂的作用。从背侧前额叶皮层（DLPFC）中降低DARPP-32表达的总证据精神分裂症患者和来自DARPP-32遗传缺失或在DARPP-32磷酸化位点具有遗传缺失或点突变的小鼠的异常表明，研究Darpp-32和Darpp-32之间的关联是值得的精神分裂症。在本研究中，我们基因分型在五个中的五个单核苷酸多态性（SNP）PPP1R1Bgene and conducted a case-control study involving 520精神分裂症patients and 386 healthy subjects drawn from the Chinese population. No allelic, genotypic or haplotypic association was found. However, our results do not preclude the possibility that thePPP1R1B是一个易感基因精神分裂症在中国人口中，由于作为中央分子开关，PPP1R1B可能会贡献精神分裂症by interacting with other genes. Further functional analysis and genetic association studies are needed to determine the potential roles ofPPP1R1B以及其他相关基因的病理生理学精神分裂症。 |
| SCZ关键字 | 精神分裂症, schizophrenic |
| 3 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2007 Aug 31: 1303-6 |
| PMID | 17618027 |
| 标题 | An association study between PPP1R1B gene and schizophrenia in the Chinese population. |
| Abstract | 精神分裂症与谷氨酸能，多巴胺能和血清素能神经传递的功能障碍有关。相对分子质量32 kDa（DARPP-32）的多巴胺和cAMP调节的磷蛋白，由编码PPP1R1B（蛋白质磷酸酶1，调节/抑制剂亚基1B）基因富含新纹状体培养基神经元。它在多巴胺能和谷氨酸能信号通路中起关键调节剂的作用。从背侧前额叶皮层（DLPFC）中降低DARPP-32表达的总证据精神分裂症患者和来自DARPP-32遗传缺失或在DARPP-32磷酸化位点具有遗传缺失或点突变的小鼠的异常表明，研究Darpp-32和Darpp-32之间的关联是值得的精神分裂症。在本研究中，我们基因分型在五个中的五个单核苷酸多态性（SNP）PPP1R1Bgene and conducted a case-control study involving 520精神分裂症patients and 386 healthy subjects drawn from the Chinese population. No allelic, genotypic or haplotypic association was found. However, our results do not preclude the possibility that thePPP1R1B是一个易感基因精神分裂症在中国人口中，由于作为中央分子开关，PPP1R1B可能会贡献精神分裂症by interacting with other genes. Further functional analysis and genetic association studies are needed to determine the potential roles ofPPP1R1B以及其他相关基因的病理生理学精神分裂症。 |
| SCZ关键字 | 精神分裂症, schizophrenic |
| 4 | 精神分裂。res。2008年8月103日：192-200 |
| PMID | 18573638 |
| 标题 | 在患有精神分裂症的完整自杀受害者中，减少了前额叶皮层DARPP-32 mRNA。 |
| Abstract | Dopamine-and-cAMP-regulated neuronal phosphoprotein (32 kDa) (DARPP-32), encoded byPPP1R1B, is expressed in brain regions receiving dopaminergic projections, including the prefrontal cortex (PFC), and is implicated in the pathophysiology of精神分裂症。The broad functional capacity of DARPP-32 has potential relevance to both psychotic and negative symptoms of精神分裂症。We wished to determine if DARPP-32 gene expression and variation at selected SNPs correlated significantly with patient phenotypes. We performed RT-PCR to quantify DARPP-32 mRNA from brain samples (Brodmann Area 46) donated by the Stanley Medical Research Institute (SMRI, Array Collection): 35 from unaffected controls (UC), 35 from patients with精神分裂症(SCZ), and 35 with bipolar disorder (BP). Relative mRNA expression was calculated in relation to the housekeeping gene Cyclophilin. SNP genotyping was conducted by PCR on DNA obtained from Brodmann Area 46. We found a significant difference in gene expression levels between SCZ patients who died by suicide (SCZ-S) (n=6) vs. other causes of death (SCZ-NS) (P<0.004), as well as between SCZ-S and UC (P<0.04). We genotyped the intron SNP rs907094 and found that the SCZ-S group was more similar to UC than to the SCZ-NS population. DARPP-32 expression differences between SCZ-S, SCZ-NS, and UC populations are consistent with previous literature suggesting that serotonin system components are also altered in suicide. Work in a larger sample is needed to confirm these findings. |
| SCZ关键字 | 精神分裂症, schizophrenic |
| 5 | 精神分裂。res。2008年3月100日：334-41 |
| PMID | 18055181 |
| 标题 | 日本精神分裂症或躁郁症患者中DARPP-32（PPP1R1B）的基因编码的遗传分析。 |
| Abstract | 几条证据，包括全基因组的连锁扫描和对患者的死后脑研究精神分裂症或双相情感障碍，表明DARPP-32（多巴胺和cAMP调节的磷蛋白，32 kDa）是多巴胺能信号通路中的关键调节分子，参与了这些疾病。在评估了编码DARPP-32的基因的连锁不平衡模式之后（PPP1R1B;位于2012年1月17日），对该基因进行了关联分析精神分裂症和躁郁症。Single-marker and haplotypic analyses of four single nucleotide polymorphisms (SNPs; rs879606, rs12601930, rs907094, and rs3764352) in a sample set (subjects with精神分裂症= 384，患有双相情感障碍的受试者= 318，对照对象= 384）表明PPP1R1B多态性与精神分裂症, whereas, even after Bonferroni corrections, significant associations with bipolar disorder were observed for rs12601930 (corrected genotypic p=0.00059) and rs907094 (corrected allelic p=0.040). We, however, could not confirm these results in a second independent sample set (subjects with bipolar disorder=366, control subjects=370). We now believe that the significant association observed with the first sample set was a result of copy number aberrations in the region surrounding these SNPs. Our findings suggest thatPPP1R1BSNP不太可能与精神分裂症和日本人口中的躁郁症。 |
| SCZ关键字 | 精神分裂症, schizophrenic |
| 6 | Behav. Brain Res. 2009 Sep 202: 179-83 |
| PMID | 19463699 |
| 标题 | 愤怒的生物学基础：与DARPP-32（PPP1R1B）的基因编码和杏仁核量的关联。 |
| Abstract | 最近的发现强调了DARPP-32（多巴胺和cAMP调节的磷蛋白，32 kDa）的重要性，这是多巴胺能信号传导途径在多巴胺相关的表型中的关键调节分子，例如抗异构 - 行为，吸毒和吸毒和吸毒和吸毒和吸毒和药物成瘾和吸毒和型表型精神分裂症。This is the first study investigating the role of the DARPP-32 gene for personality. In a sample of n=838 healthy German Caucasian subjects we found a significant association between rs907094 and ANGER. Carriers of the T-allele showed significantly higher ANGER scores than participants without a T-allele (F((1,837))=9.52, p=0.002). In a second step we validated self-report data of ANGER by investigating their relation to structural brain differences in anger-related brain regions using voxel-based morphometry. A negative association between ANGER scores and the volume of the left amygdala could be detected. The present findings yield genetic evidence for the importance of dopaminergic signal transduction for the personality trait of ANGER. In addition volumetric MRI data support the role of the amygdala for the processing of anger. |
| SCZ关键字 | 精神分裂症, schizophrenic |
| 7 | 精神病学水库2010年9月179日：126-9 |
| PMID | 20483474 |
| 标题 | Testing the antagonistic pleiotropy model of schizophrenia susceptibility by analysis of DAOA, PPP1R1B, and APOL1 genes. |
| Abstract | 精神分裂症是一种与生育能力降低有关的常见疾病。因此，没有自然选择去除的常见易感性等位基因的存在可能被认为是进化悖论。提议解释这种悖论的拮抗性多效模型指出，尽管对特定性状产生了有害的影响，但由于其总体选择性优势，等位基因可能很常见。关于daoa的最新工作，PPP1R1B, and APOL1 suggests that these genes present common alleles associated to increase risk of精神分裂症但是，赋予与更好的认知表现有关的总体选择优势（DAOA和PPP1R1B）或防止病原体（APOL1）。为了测试这些基因是否符合拮抗性多效性模型，我们在这些基因座上搜索了最新的自然选择，并在HAPMAP项目的数据上采用了远程单倍型测试。并在功能齐全的样本中进行了病例对照的关联分析，包括301精神分裂症patients and 604 controls from Spain. For DAOA andPPP1R1B,我们的基因单核苷酸多态性(SNPs) needed to replicate previous associations, while for APOL1, we genotyped 15 tagSNPs, and seven putative functional SNPs. We did not detect evidence of recent natural selection. Furthermore, we did not find significant associations. Thus, these genes do not fit the antagonistic pleiotropy model. |
| SCZ关键字 | 精神分裂症, schizophrenic |
| 8 | 精神病学水库2010年9月179日：126-9 |
| PMID | 20483474 |
| 标题 | Testing the antagonistic pleiotropy model of schizophrenia susceptibility by analysis of DAOA, PPP1R1B, and APOL1 genes. |
| Abstract | 精神分裂症是一种与生育能力降低有关的常见疾病。因此，没有自然选择去除的常见易感性等位基因的存在可能被认为是进化悖论。提议解释这种悖论的拮抗性多效模型指出，尽管对特定性状产生了有害的影响，但由于其总体选择性优势，等位基因可能很常见。关于daoa的最新工作，PPP1R1B, and APOL1 suggests that these genes present common alleles associated to increase risk of精神分裂症但是，赋予与更好的认知表现有关的总体选择优势（DAOA和PPP1R1B）或防止病原体（APOL1）。为了测试这些基因是否符合拮抗性多效性模型，我们在这些基因座上搜索了最新的自然选择，并在HAPMAP项目的数据上采用了远程单倍型测试。并在功能齐全的样本中进行了病例对照的关联分析，包括301精神分裂症patients and 604 controls from Spain. For DAOA andPPP1R1B,我们的基因单核苷酸多态性(SNPs) needed to replicate previous associations, while for APOL1, we genotyped 15 tagSNPs, and seven putative functional SNPs. We did not detect evidence of recent natural selection. Furthermore, we did not find significant associations. Thus, these genes do not fit the antagonistic pleiotropy model. |
| SCZ关键字 | 精神分裂症, schizophrenic |
| 9 | Front Behav Neurosci 2011 -1 5: 56 |
| PMID | 21927600 |
| 标题 | Darpp-32，所有交易的杰克？主人？ |
| Abstract | DARPP-32 (PPP1R1B）被发现是富含多巴胺脑区域的cAMP依赖性蛋白激酶（PKA）的底物。它是蛋白质磷酸酶-1（PP1）的三个相关，PKA调节的抑制剂之一。这些抑制剂似乎已经出现在早期的脊椎动物祖先中，可能是gnathostomes。DARPP-32具有其他重要的生物化学特性，包括当通过CDK5磷酸化和酪蛋白激酶1和2调节时，包括PKA的抑制作用。它在特定的神经元群体中高度富集，尤其是纹状体中型中型棘神经元。随着PP1抑制剂DARPP-32的放大和/或介导PKA在质膜和细胞质中的许多作用，具有广泛的潜在靶标和功能。Darpp-32还经历了连续且受到严格调节的西托核穿梭。这种贩运是由Ser-97的磷酸化控制的，Ser-97是核出口所必需的。当在THR-34上磷酸化并在SER-97上磷酸化时，DARPP-32可以抑制细胞核中的PP1，并调节染色质反应调节的调节信号传导途径。最近使用多个转基因和基因敲除突变体小鼠的工作允许在纹状体和纹状体 - 帕利德神经元中解剖DARPP-32功能。它与治疗和滥用精神活性药物的作用有关，前额叶皮层功能和性行为。 However, the contribution of DARPP-32 in human behavior remains poorly understood. Post-mortem studies in humans suggest possible alterations of DARPP-32 levels in精神分裂症和躁郁症。遗传研究揭示了与心理学和心理病理学特征可能相关的多态性。此外，Darpp-32（T-DARPP）的短同工型在癌症中起作用，表明其他信号传导特性。因此，DARPP-32是一种不必要但密切调节的信号轮毂分子，可以改善表达其表达的神经元电路的一般性能。 |
| SCZ关键字 | 精神分裂症, schizophrenic |
| 10 | PLOS ONE 2012 -1 7：E36561 |
| PMID | 22615781 |
| 标题 | Candidate gene-based association study of antipsychotic-induced movement disorders in long-stay psychiatric patients: a prospective study. |
| Abstract | Four types of antipsychotic-induced movement disorders: tardive dyskinesia (TD), parkinsonism, akathisia and tardive dystonia, subtypes of TD (orofacial and limb truncal dyskinesia), subtypes of parkinsonism (rest tremor, rigidity, and bradykinesia), as well as a principal-factor of the movement disorders and their subtypes, were examined for association with variation in 10 candidate genes (PPP1R1B，BDNF，DRD3，DRD2，HTR2A，HTR2C，COMT，MNSOD，CYP1A2和RGS2）。 Naturalistic study of 168 white long-stay patients with chronic mental illness requiring long-term antipsychotic treatment, examined by the same rater at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. The authors genotyped 31 SNPs, associated with movement disorders or精神分裂症在先前的研究中。基因型和等位基因频率比较是使用多个回归方法进行连续运动障碍进行的。 各种SNP具有名义意义：带有RS6265和RS988748的TD和Orofacial Edkinesia，带有RS6314的肢体弯曲障碍，带有RS6275的Rest Tremor，具有RS6265和RS4680和RS4680的刚度与RS4680，与RS477777995390的僵化，rs6265和RS4680。在控制多次测试之后，没有任何显着结果。 The findings suggest that selected SNPs are not associated with a susceptibility to movement disorders. However, as the sample size was small and previous studies show inconsistent results, definite conclusions cannot be made. Replication is needed in larger study samples, preferably in longitudinal studies which take the fluctuating course of movement disorders and gene-environment interactions into account. |
| SCZ关键字 | 精神分裂症, schizophrenic |
| 11 | Int. J. Dev. Neurosci. 2013 May 31: 189-95 |
| PMID | 23313435 |
| 标题 | 产后孕产妇剥夺和青春期应激对纹状体中多巴胺D2受体和CAMKIIβ表达具有附加作用。 |
| Abstract | 本研究的目的是确定whether two stressors commonly used to model aspects of neuropsychiatric disease in rats have an additive effect on striatal dopamine type 2 receptor (D2R) expression, a key player in the etiology of neuropsychiatric disease. Animals subjected to early postnatal stress show alterations in function of the dopaminergic system thought to be mediated by stress-induced glucocorticoid release. Subsequent stress during puberty is known to further impact the dopaminergic system and result in dopaminergic hyperactivity analogous to精神分裂症。We exposed rats to maternal deprivation (MD) during the second postnatal week, a time of active striatal development. A subset of these animals were then subjected to pubertal stress induced by immobilization. Both procedures are know to induce glucocorticoid release. At the conclusion of the MD protocol, we observed upregulation in the expression of D2R and of dopamine- and cAMP-regulated phosphoprotein 32-KD (DARPP-32;PPP1R1B），但不为D1R，钙/钙调蛋白依赖性蛋白激酶IIβ（CAMKII？），CAMKII？或Neurokinin B（NKB）。暴露于青春期胁迫的动物在D2R和CaMKII的表达中表现出上调。此外，以前暴露于MD的大鼠在CAMKII中表现出更大的上调？表达，而不是暴露于青春期应激的动物。这些结果支持两次打击的假设，表明这种应激源具有加性效果。主要目标似乎是D2R和CAMKII？，后者是DR信号通路的重要成员，两者都与精神分裂症。 |
| SCZ关键字 | 精神分裂症, schizophrenic |
| 12 | Mol. Psychiatry 2014 Feb 19: 192-9 |
| PMID | 23295814 |
| 标题 | 重新审视DARPP-32在尸体后人脑中：精神分裂症和双相情感障碍以及与T-DARPP-32表达的遗传关联的变化。 |
| Abstract | Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32 orPPP1R1B）很感兴趣精神分裂症由于其在整合多巴胺能和谷氨酰胺能信号传导中的关键功能。在先前的研究中，我们鉴定了单核苷酸多态性（SNP）和与已与认知和成像表型相关的频繁的单倍型精神分裂症以及在相对较小的尸体大脑样本中的前额叶皮质DARPP-32信使RNA（mRNA）的表达。在这项研究中，我们检查了两个主要的DARPP-32转录本的表达（FL-DARPP-32）和截短（T-DARPP-32）的表达相关性，而Darpp-32的遗传变异在三个大脑区域接受了遗传变异。多巴胺能输入并与精神分裂症(the dorsolateral prefrontal cortex (DLPFC), hippocampus and caudate) in a much larger set of postmortem samples from patients with精神分裂症，躁郁症，重度抑郁症和正常对照（> 700名受试者）。我们发现，在患有DLPFC的患者的DLPFC中，T-DARPP-32的表达增加了精神分裂症和双相情感障碍，并且与SNP的基因型密切相关（RS879606，RS90974和RS3764352），以及先前鉴定的与认知功能相关的7-SNP单倍型。预测认知性能较差的遗传变异与较高的T-DARPP-32表达有关。我们的结果表明差异PPP1R1B影响剪接变体T-DARPP-32 mRNA的丰度，并可能反映了涉及的潜在分子机制精神分裂症和情感障碍。 |
| SCZ关键字 | 精神分裂症, schizophrenic |
| 13 | Oncotarget 2016 2月1日：-1 |
| PMID | 26872373 |
| 标题 | DARPP-32: from neurotransmission to cancer. |
| Abstract | 多巴胺和cAMP调节的磷蛋白MR 32,000（DARPP-32），也称为磷酸蛋白磷酸酶-1调节亚基1B（PPP1R1B), was initially discovered as a substrate of dopamine-activated protein kinase A (PKA) in the neostriatum in the brain. While phosphorylation at Thr-34 by PKA converts DARPP-32 into a potent inhibitor of protein phosphatase 1 (PP1), phosphorylation at Thr-75 transforms DARPP-32 into an inhibitor of PKA. Through regulation of DARPP-32 phosphorylation and modulation of protein phosphatase and kinase activities, DARPP-32 plays a critical role in mediating the biochemical, electrophysiological, and behavioral effects controlled by dopamine and other neurotransmitters in response to drugs of abuse and psychostimulants. Altered expression of DARPP-32 and its truncated isoform (t-DARPP), specifically in the prefrontal cortex, has been associated with精神分裂症和躁郁症。Moreover, cleavage of DARPP-32 by calpain has been implicated in Alzheimer's disease. Amplification of the genomic locus of DARPP-32 at 17q12 has been described in several cancers. DARPP-32 and t-DARPP are frequently overexpressed at the mRNA and protein levels in adenocarcinomas of the breast, prostate, colon, and stomach. Several studies demonstrated the pro-survival, pro-invasion, and pro-angiogenic functions of DARPP-32 in cancer. Overexpression of DARPP-32 and t-DARPP also promotes chemotherapeutic drug resistance and cell proliferation in gastric and breast cancers through regulation of pro-oncogenic signal transduction pathways. The expansion of DARPP-32 research from neurotransmission to cancer underscores the broad scope and implication of this protein in disparate human diseases. |
| SCZ关键字 | 精神分裂症, schizophrenic |