| 1 | Neuroreport 2004 Aug 15: 1965-7 |
|---|---|
| PMID | 15305146 |
| Title | Association study of PICK1 rs3952 polymorphism and schizophrenia. |
| 抽象的 | Protein interacting with C-kinase-1 (PICKl) plays an important role in the targeting and clustering of neuronal receptors and amine transporters. ThePICK1gene may play a role in conferring susceptibility to精神分裂症as it has been mapped to chromosome 22q13.1, a region thought to contain a gene for精神分裂症。我们检验了以下假设PICK1基因与诊断有关精神分裂症。这PICK1rs3952 polymorphism was genotyped in 225精神分裂症and 260 controls. Results demonstrated that thePICK1rs3952 genotype and allele distribution was significantly different between the two groups. The positive association suggests that thePICK1gene may play a role in the pathogenesis of精神分裂症。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 2 | J. Neurosci。res。2005年3月79日：868-78 |
| PMID | 15696539 |
| Title | mRNA expression of AMPA receptors and AMPA receptor binding proteins in the cerebral cortex of elderly schizophrenics. |
| 抽象的 | L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate the majority of the fast excitatory transmission in the CNS. To determine whether gene expression of AMPARs and/or AMPAR binding proteins, which control response/sensitivity of AMPAR-bearing neurons to glutamate, are altered in精神分裂症, mRNA expression and abundance of AMPAR subunits (GluR1-4) and several AMPAR binding proteins (SAP97,PICK1，在背侧前额叶皮层（DLPFC）和老年人的枕皮层中测量抓地力，ABP）精神分裂症patients (n = 36) and matched normal controls (n = 26) by quantitative real-time PCR. The mRNA expression of GluR1, GluR4, and GRIP in the DLPFC and expression of the GluR4, GRIP, and ABP in the occipital cortex were significantly elevated in精神分裂症s. GluR1 and ABP mRNA expression in the occipital cortex and GluR2, GluR3, SAP97, andPICK1expression in either cortical area were not significantly altered. The data also demonstrated significant differences in the abundances of mRNAs encoding GluR1-4 subunits (GluR2 > GluR3 > GluR1 > GluR4) and of AMPAR binding proteins (SAP97 >PICK1> grip> abp）在两个诊断组中。GLUR2（58-64％）和GlUR3（24-29％）是两个皮质区域中AMPAR mRNA的主要成分，这意味着人皮质中的主要AMPAR复合物可能是含有GlUR2和GlUR3亚基的AMPAR复合物。在两个皮质区域之间检测到GLUR2，GLUR3和GRIP mRNA的量很小但显着差异：在DLPFC中比枕骨皮层中检测到的GLUR3和握力更多，但在DLPFC中检测到较少的GLUR2。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 3 | J. Neurosci。res。2005年3月79日：868-78 |
| PMID | 15696539 |
| Title | mRNA expression of AMPA receptors and AMPA receptor binding proteins in the cerebral cortex of elderly schizophrenics. |
| 抽象的 | L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate the majority of the fast excitatory transmission in the CNS. To determine whether gene expression of AMPARs and/or AMPAR binding proteins, which control response/sensitivity of AMPAR-bearing neurons to glutamate, are altered in精神分裂症, mRNA expression and abundance of AMPAR subunits (GluR1-4) and several AMPAR binding proteins (SAP97,PICK1，在背侧前额叶皮层（DLPFC）和老年人的枕皮层中测量抓地力，ABP）精神分裂症patients (n = 36) and matched normal controls (n = 26) by quantitative real-time PCR. The mRNA expression of GluR1, GluR4, and GRIP in the DLPFC and expression of the GluR4, GRIP, and ABP in the occipital cortex were significantly elevated in精神分裂症s. GluR1 and ABP mRNA expression in the occipital cortex and GluR2, GluR3, SAP97, andPICK1expression in either cortical area were not significantly altered. The data also demonstrated significant differences in the abundances of mRNAs encoding GluR1-4 subunits (GluR2 > GluR3 > GluR1 > GluR4) and of AMPAR binding proteins (SAP97 >PICK1> grip> abp）在两个诊断组中。GLUR2（58-64％）和GlUR3（24-29％）是两个皮质区域中AMPAR mRNA的主要成分，这意味着人皮质中的主要AMPAR复合物可能是含有GlUR2和GlUR3亚基的AMPAR复合物。在两个皮质区域之间检测到GLUR2，GLUR3和GRIP mRNA的量很小但显着差异：在DLPFC中比枕骨皮层中检测到的GLUR3和握力更多，但在DLPFC中检测到较少的GLUR2。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 4 | Synapse 2006 Dec 60: 585-98 |
| PMID | 16983646 |
| Title | Lamina-specific abnormalities of AMPA receptor trafficking and signaling molecule transcripts in the prefrontal cortex in schizophrenia. |
| 抽象的 | Ampakines, positive AMPA receptor modulators, can improve cognitive function in精神分裂症, and enhancement of AMPA receptor-mediated currents by them potentiates the activity of antipsychotics. In vitro studies have revealed that trafficking of AMPA receptors is mediated by specific interactions of a complex network of proteins that also target and anchor them at the postsynaptic density (PSD). The aim of this study was to determine whether there are abnormalities of the molecules associated with trafficking and localization of AMPA receptors at the PSD in the dorsolateral prefrontal cortex (DLPFC) in精神分裂症。We analyzed AMPA receptor expression in DLPFC in精神分裂症通过原位杂交检查所有四个AMPA受体亚基的转录水平，这是重度抑郁症，双相情感障碍和对照组。我们发现在所有三种疾病中GLUR2亚基的表达降低，在严重抑郁症中降低了GLUR3，而GLUR4降低了精神分裂症。However, autoradiography experiments showed no changes in AMPA receptor binding; thus, we hypothesized that these changes in receptor subunit stoichiometry do not alter binding to the assembled receptor, but rather intracellular processing. In situ hybridization for AMPA-trafficking molecules showed decreased expression ofPICK1并增加Stargazin在DLPFC中的表达精神分裂症, both restricted to large cells of cortical layer III. These data suggest that AMPA-mediated glutamatergic neurotransmission is compromised in精神分裂症, particularly at the level of AMPA-related PSD proteins that mediate AMPA receptor trafficking, synaptic surface expression, and intracellular signaling. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 5 | 趋势Pharmacol。科学。2006年11月27日：574-9 |
| PMID | 17011050 |
| Title | 这精神分裂症faces of PICK1. |
| 抽象的 | 精神分裂症is a grave psychiatric disorder with psychotic symptoms and an enigmatic etiology. Family studies have strongly indicated that genetic risk factors have a role in this disease. Recent findings, together with previously established evidence, highlight the PDZ-domain-containing protein interacting with C-kinase 1 (PICK1) as a promising candidate for a精神分裂症susceptibility gene. Here, we outline possible molecular mechanisms, discuss clinical case-studies that indicate an unexpected role ofPICK1in精神分裂症and discuss potential avenues for pharmacological manipulation ofPICK1。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 6 | 趋势Pharmacol。科学。2006年11月27日：574-9 |
| PMID | 17011050 |
| Title | 这精神分裂症faces of PICK1. |
| 抽象的 | 精神分裂症is a grave psychiatric disorder with psychotic symptoms and an enigmatic etiology. Family studies have strongly indicated that genetic risk factors have a role in this disease. Recent findings, together with previously established evidence, highlight the PDZ-domain-containing protein interacting with C-kinase 1 (PICK1) as a promising candidate for a精神分裂症susceptibility gene. Here, we outline possible molecular mechanisms, discuss clinical case-studies that indicate an unexpected role ofPICK1in精神分裂症and discuss potential avenues for pharmacological manipulation ofPICK1。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 7 | Mol. Psychiatry 2006 Feb 11: 150-7 |
| PMID | 16314870 |
| Title | 丝氨酸种族酶与Pick1结合：与精神分裂症的潜在相关性。 |
| 抽象的 | Accumulating evidence from both genetic and clinico-pharmacological studies suggests that D-serine, an endogenous coagonist to the NMDA subtype glutamate receptor, may be implicated in精神分裂症(SZ). Although an association of genes for D-serine degradation, such as D-amino acid oxidase and G72, has been reported, a role for D-serine in SZ has been unclear. In this study, we identify and characterize protein interacting with C-kinase (PICK1) as a protein interactor of the D-serine synthesizing enzyme, serine racemase (SR). The binding of endogenousPICK1and SR requires the PDZ domain ofPICK1。这gene coding forPICK1is located at chromosome 22q13, a region frequently linked to SZ. In a case-control association study using well-characterized Japanese subjects, we observe an association of thePICK1与深圳基因,在d更突出isorganized SZ. Our findings implicatingPICK1作为SZ的敏感基因，与D链在该疾病中的作用一致。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 8 | Neurosci. Res. 2007 Jun 58: 145-8 |
| PMID | 17367885 |
| Title | PICK1 is not a susceptibility gene for schizophrenia in a Japanese population: association study in a large case-control population. |
| 抽象的 | 蛋白质与C-激酶1相互作用（PICK1) has been implicated in the susceptibility to精神分裂症。PICK1interacts with enzymes and receptors that play roles in the pathogenesis of精神分裂症via glutamatergic dysfunction. Recently, two studies reported associations between精神分裂症和两个PICK1gene polymorphisms, rs3952 in Chinese and Japanese populations and rs2076369 in a Japanese population. We attempted to confirm these associations in a case-control study of 1765 Japanese patients with精神分裂症and 1851 Japanese control subjects. Neither polymorphism was associated with精神分裂症（RS3952，p = 0.755; rs2076369，p = 0.997）。具有这些多态性的单倍型块，跨越了该区域的5'区域PICK1gene showed high linkage disequilibrium in the Japanese population (D'=0.98, r(2)=0.34); however, neither haplotype was significantly associated with精神分裂症。We conclude that the common haplotypes and polymorphisms of thePICK1迄今为止鉴定出的基因不太可能有助于遗传易感性精神分裂症in the Japanese population. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 9 | Biol. Psychiatry 2008 May 63: 997-1000 |
| PMID | 18191108 |
| Title | 在缺乏pick1的小鼠大脑中D丝氨酸水平的调节。 |
| 抽象的 | D-serine is an endogenous coagonist of the N-methyl-D-aspartate subtype glutamate receptor. Genetic association studies have implicated genes coding for enzymes associated with D-serine metabolism in精神分裂症and bipolar disorder. Protein expression of serine racemase (SR) and its binding partner, protein interacting with C-kinase (PICK1), were examined by Western blotting in brains from wildtype andPICK1knockout mice. Levels of D-serine in wildtype andPICK1还通过已建立的高压液相色谱方案检查小鼠。 SR的表达PICK1蛋白质受发展调节。尽管在SR蛋白水平上未观察到任何变化，但在新生儿的前脑中选择性降低了D-丝氨酸的水平PICK1knockout mice, compared with those in wildtype mice. PICK1可能以空间和时间特定的方式参与大脑D丝氨酸水平和SR的调节。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 10 | J. Neurochem. 2008 Aug 106: 1027-34 |
| PMID | 18429931 |
| Title | Zinc binding site in PICK1 is dominantly located at the CPC motif of its PDZ domain. |
| 抽象的 | PICK1(protein interacting with Ckinase 1) containing a PDZ domain, a BAR domain, and two short acidic regions is as an adaptor protein that plays an important role in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor trafficking, cell morphology and migration, as well as in some diseases such as cancer,精神分裂症和痛苦。更好地了解PICK1, we expressed the recombinantPICK1及其在大肠杆菌中的截短突变体，并通过荧光和竞争测定法测量了其锌结合特性。结果表明PICK1has one Zn2+-binding site. The Zn2+-binding properties ofPICK1are not appreciably affected after the removal of BARC domain (involving BAR domain and C-terminal acidic region). Deleting the N-terminal acidic region of NPDZ domain (involving PDZ domain and N-terminal acidic region) inPICK1impairs its Zn2+-binding capacity. The mutation of the CPC (Cys-Pro-Cys) motif in the PDZ domain ofPICK1abolishes the ability of Zn2+-binding. In addition, Zn2+ can enhance the lipid-binding ability of PDZ domain as observed in both protein-lipid overlay assay and fluorescence analysis. The results presented in this report suggested that Zn2+ plays a regulatory role in the trafficking ofPICK1从细胞质到细胞膜。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 11 | Schizophr. Res. 2010 Jul 120: 236-7 |
| PMID | 20385472 |
| Title | Elevated PICK1 mRNA in schizophrenia increased SRR mRNA in suicide. |
| 抽象的 | -1 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 12 | Proteins 2012 May 80: 1393-408 |
| PMID | 22275068 |
| Title | 这binding affinities of proteins interacting with the PDZ domain of PICK1. |
| 抽象的 | Protein interacting with C kinase (PICK1）在整个进化过程中都是充分保守的，并且通过调节其相互作用蛋白的运输和翻译后修饰，在突触可塑性中起关键作用。PICK1contains a single PSD95/DlgA/Zo-1 (PDZ) protein-protein interaction domain, which is promiscuous and shown to interact with over 60 proteins, most of which play roles in neuronal function. Several reports have suggested the role ofPICK1在癫痫，疼痛，脑部创伤和中风，药物滥用和依赖等疾病中，精神分裂症and psychosis. Importantly, lead compounds that blockPICK1interactions are also now becoming available. Here, a new modeling approach was developed to investigate binding affinities of PDZ interactions. Using these methods, the binding affinities of all majorPICK1报道了相互作用的蛋白质PICK1描述了这些相互作用的突变。这些建模方法在定义与蛋白质相互作用的结合特性方面具有重要意义PICK1as well as the general structural requirements of PDZ interactions. The study also provides modeling methods to support in the drug design of ligands for PDZ domains, which may further aid in development of the family of PDZ domains as a drug target. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 13 | PLOS ONE 2013 -1 8：E70302 |
| PMID | 23936182 |
| Title | Population-specific haplotype association of the postsynaptic density gene DLG4 with schizophrenia, in family-based association studies. |
| 抽象的 | 这post-synaptic density (PSD) of glutamatergic synapses harbors a multitude of proteins critical for maintaining synaptic dynamics. Alteration of protein expression levels in this matrix is a marked phenomenon of neuropsychiatric disorders including精神分裂症，认知功能受损的地方。研究在PSD中表达的基因的遗传关系精神分裂症, a family-based association analysis of genetic variants in PSD genes such as DLG4, DLG1,PICK1and MDM2, was performed, using Japanese samples (124 pedigrees, n = 376 subjects). Results showed a significant association of the rs17203281 variant from the DLG4 gene, with preferential transmission of the C allele (p = 0.02), although significance disappeared after correction for multiple testing. Replication analysis of this variant, found no association in a Chinese精神分裂症群组(293谱系,n = 1163)或在一个Japanese case-control sample (n = 4182 subjects). The DLG4 expression levels between postmortem brain samples from精神分裂症患者对对照没有明显变化。Interestingly, a five marker haplotype in DLG4, involving rs2242449, rs17203281, rs390200, rs222853 and rs222837, was enriched in a population specific manner, where the sequences A-C-C-C-A and G-C-C-C-A accumulated in Japanese (p = 0.0009) and Chinese (p = 0.0007)精神分裂症pedigree samples, respectively. However, this could not be replicated in case-control samples. None of the variants in other examined candidate genes showed any significant association in these samples. The current study highlights a putative role for DLG4 in精神分裂症pathogenesis, evidenced by haplotype association, and warrants further dense screening for variants within these haplotypes. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 14 | Mol. Psychiatry 2013 May 18: 557-67 |
| PMID | 22801410 |
| Title | Pathogenic disruption of DISC1-serine racemase binding elicits schizophrenia-like behavior via D-serine depletion. |
| 抽象的 | Perturbation of Disrupted-In-精神分裂症-1(DISC1) and D-serine/NMDA receptor hypofunction have both been implicated in the pathophysiology of精神分裂症和其他精神疾病。在本研究中，我们证明了这两种途径与行为后果相交。Disc1结合并稳定丝氨酸种族酶（SR），丝氨酸种族酶（SR）生成了D-Serine（NMDA受体的内源性共振）D-Serine的酶。突变盘1无法与SR结合，促进SR的泛素化和降解以及D- serine产生的降低。为了阐明体内的盘1-SR相互作用，我们在星形胶质细胞中生成了突变盘1的选择性和可诱导表达的小鼠模型，这是大脑中D丝氨酸的主要来源。突变盘1的表达下调内源性盘并降低蛋白质，但不能降低SR的mRNA水平，从而导致D-丝氨酸的产生减少。相反，突变盘1不会改变disc1和sr，lis1或PICK1。成年雄性和雌性老鼠一生的表达ion of mutant DISC1 exhibit behavioral abnormalities consistent with hypofunction of NMDA neurotransmission. Specifically, mutant mice display greater responses to an NMDA antagonist, MK-801, in open field and pre-pulse inhibition of the acoustic startle tests and are significantly more sensitive to the ameliorative effects of D-serine. These findings support a model wherein mutant DISC1 leads to SR degradation via dominant negative effects, resulting in D-serine deficiency that diminishes NMDA neurotransmission thus linking DISC1 and NMDA pathophysiological mechanisms in mental illness. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 15 | Synapse 2013 Aug 67: 532-40 |
| PMID | 23436724 |
| Title | Protein interacting with C kinase and neurological disorders. |
| 抽象的 | Best known for its interaction with the ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluA2 and for its influence on excitatory synapse activity, the protein interacting with C kinase,PICK1, is the focus of considerable attention from neurobiologists. Indeed, this PSD-95/DlgA/ZO-1 (PDZ) domain-containing protein has been shown to interact with a wide variety of neurotransmitter receptors, transporters, and enzymes, including glutamate and nicotinic acetylcholine receptors, dopamine and glutamate transporters, and the enzyme serine racemase. Through its lipid binding domain,PICK1is targeted to the inner surface of the cell membrane where it contributes to anchoring these partners and thereby influences their synaptic localization and function. Under pathological conditions, the regulation of somePICK1-interacting partners is altered, pointing to an involvement ofPICK1in neurological disorders. Also, genetic or pharmacological manipulations ofPICK1expression, localization, or function have been shown to influence several physiological or pathological processes in which putativePICK1partners are involved. This review will summarize recent experimental observations that highlight the involvement ofPICK1in neurological disorders, including精神分裂症、帕金森病、癫痫、慢性疼痛,德鲁g abuse, and amyotrophic lateral sclerosis. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 16 | J. Neurosci。2015 Apr 35: 6429-43 |
| PMID | 25904794 |
| Title | Protein Interacting with C-Kinase 1 Deficiency Impairs Glutathione Synthesis and Increases Oxidative Stress via Reduction of Surface Excitatory Amino Acid Carrier 1. |
| 抽象的 | Protein interacting with C-kinase 1 (PICK1) has received considerable attention, because it interacts with a broad range of neurotransmitter receptors, transporters, and enzymes and thereby influences their localization and function in the CNS. Although it is suggested that putative partners ofPICK1are involved in neurological diseases such as精神分裂症, Parkinson's disease, chronic pain, and amyotrophic lateral sclerosis, the functions ofPICK1in neurological disorders are not clear. Here, we show that oxidative stress, which is tightly associated with neurological diseases, occurs inPICK1(-/-) mice. The oxidation inPICK1(-/-) mice was found selectively in neurons and was age dependent, leading to microglial activation and the release of inflammatory factors. Neurons in the cortex and hippocampus fromPICK1(-/-) mice showed increased vulnerability to oxidants and reduced capacity to metabolize reactive oxygen species (ROS); this was caused by reduced glutathione content and impaired cysteine transport. The dysregulated expression of glutathione was attributed to a decrease of the surface glutamate transporter excitatory amino acid carrier 1 (EAAC1). Overexpression ofPICK1可以挽救EAAC1的表面表达，并改善谷胱甘肽的缺陷PICK1(-/-) neurons. Finally, reduced surface EAAC1 was associated with defective Rab11 activity. Transfection with dominant-negative Rab11 effectively suppressed surface EAAC1 and increased ROS production. Together, these results indicate thatPICK1is a crucial regulator in glutathione homeostasis and may play important roles in oxidative stress and its associated neurodegenerative diseases. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 17 | 元基因2015年9月5日：135-9 |
| PMID | 26925374 |
| Title | Secondary association of PDLIM5 with paranoid schizophrenia in Emirati patients. |
| 抽象的 | 精神分裂症is a clinically and genetically heterogeneous disorder of unknown etiology. PDLIM5 variants have been linked to精神分裂症and other related neuropsychiatric disorders and upregulated in the brain of精神分裂症patients suggesting a possible pathogenic role in disease progression. The aim of this study is to examine the potential association of精神分裂症在emirati患者中，先前报道了PDLIM5的变体PICK1, NRG3 or DISC1 genes. Consequently, we found a secondary association between PDLIM5 variants and the paranoid subtype of精神分裂症在阿拉伯人中，阿拉伯人建议PDLIM5可能代表确定/标记精神分裂症subtype specification. However, no associations were found with variants inPICK1, NRG3 or DISC1 genes. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 18 | Neurochem. Int. 2016 Mar -1: -1 |
| PMID | 26970394 |
| Title | Multiple faces of protein interacting with C kinase 1 (PICK1): Structure, function, and diseases. |
| 抽象的 | Protein interacting with C-kinase 1 (PICK1) has received considerable attention because it is the only protein that contains both PSD-95/DlgA/ZO-1 (PDZ) domain and Bin-Amphiphysin-Rvs (BAR) domain. Through PDZ and BAR domains,PICK1binds to a large number of membrane proteins and lipid molecules, and is thereby of multiple functions.PICK1is widely expressed in various tissues, particularly abundant in the brain and testis. In the central nervous system (CNS),PICK1与许多神经递质受体，转运蛋白，离子通道和酶相互作用，并控制其运输。最佳特征功能的功能PICK1它是否调节了 - 氨基-3-羟基-5-甲基异恶唑-4-丙酸酯受体（AMPAR）亚基GLUA2在长期抑郁和长期增强期间的运输。最近的证据表明PICK1participates in various diseases including neurobiological disorders, such as chronic pain, epilepsy, oxidative stress, stroke, Parkinson's disease, amyotrophic lateral sclerosis,精神分裂症, and non-neurological disorders, such as globozoospermia, breast cancer, and heart failure. In this review, we will summarize recent advances focusing on the structure and regulation ofPICK1and its functions in protein trafficking, neurological and non-neurological diseases. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |