神经突触中枢神经突触膜相关鸟甘酸激酶锚定蛋白参与疼痛调节的研究进展

背景 中枢神经突触膜相关鸟苷酸激酶(membrane-associated guanylate kinase,MAGUK)蛋白家族包含4种突触相关蛋白:PSD-93、PSD-95、SAP-102、SAP-97,它们参与调节谷氨酸突触信号传递,与学习记忆和疼痛等有关. 目的综述神经突触MAGUK锚定蛋白与疼痛相关受体和分子之间的相互作用及其在疼痛信号调节及传递中的作用. 内容 神经突触MAGUK锚定蛋白可通过与N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)受体、神经元型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)、使君子酸(α-amino-3-hydroxy-5-methy-4-isoxazole propionate,AMPA)受体以及突触细胞黏附分子(synaptic cell-adhesion molecules,Syn CAM)等相互作用参与调节疼痛信号在突触的传递,影响突触传递强度. 趋向 干扰神经突触MAGUK锚定蛋白与疼痛相关受体和重要分子间的相互作用可影响疼痛信号在突触的传递,是疼痛治疗的新靶点.     

全麻药物对突触可塑性影响的研究进展

背景 全麻药物作用于中枢神经系统的多种神经递质和受体靶点,而这些又恰恰是神经突触可塑性相关机制中的重要成分或结构,通过调节突触可塑性进而对学习记忆功能产生广泛而多样的作用. 目的 推进对全麻药物麻醉机理的认识. 内容 分析全麻药物对大脑突触可塑性影响的研究进展 趋向 为临床麻醉药物的合理使用、减少术中知晓和术后认知功能障碍等相关并发症的发生提供科学依据.     

突触功能障碍在阿尔茨海默病发病机制中的研究进展

背景神经突触具有高度可塑性,突触的形成和重塑是神经元活动依赖性的,是学习记忆、认知功能的基础。越来越多的证据表明阿尔茨海默病（alzheimer＇s disease,AD）早期出现的轻度认知功能下降与突触功能障碍相关。目的对突触功能障碍在AD发病机制中的作用作一系统阐述。内容近年来研究发现,AD患者脑内发生着明显的突触丢失的神经组织学改变,并多发生在认知缺失开始的早期;同时发现,突触的丢失程度与痴呆的严重程度密切相关,成为与认知缺失相关的一个重要的病理学特征。趋势对突触功能障碍机制的深入研究可能为AD的早期干预和治疗开拓新的思路与方向。     

血小板反应蛋白在突触形成中的作用及机制研究进展

目的对近年来血小板反应蛋白(thrombospondins,TSPs)在中枢神经系统(central nervous system,CNS)突触形成中的作用及机制进行综述。方法广泛查阅近年来与TSPs在CNS突触形成中有关的国内外文献,对TSPs结构特征、在CNS疾病中的作用及发生机制进行综述。结果 TSPs作为一种寡聚糖蛋白,在血管生成、炎症、成骨、细胞增殖和细胞凋亡等方面具有重要作用。在神经系统中,TSPs与电压依赖性钙通道、神经连接蛋白以及其他细胞外基质蛋白和细胞表面受体结合,参与和调节CNS中突触的形成、成熟以及功能等多个过程。结论 TSPs作为一种寡聚细胞外基质蛋白,在突触形成、CNS损伤后突触修复等方面发挥重要作用。     

Neuroligin1与突触活动的相互作用

背景 Neuroligin1是突触细胞黏附分子(synaptic cell adhesion molecules,SynCAM)的一种,与Neurexin1β及突触后膜致密蛋白95(postsynaptic density protein 95,PSD-95)相结合形成跨突触复合物,这一跨突触信号可以中介使君子酸(a-amino-3-hydroxy-5-methyl4-isoxazole-propionate,AMPA)受体亚基突触靶向和突触前囊泡释放,在学习、记忆和疼痛中均具有重要作用.目的 对Neuroligin1与突触活动的相互作用进行回顾与总结.内容 Neuroligin1可通过调节AMPA受体、N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体的突触靶向来参与到突触活动中;相应的,突触活动也能诱导Neuroligin1的裂解和磷酸化,使突触活动趋于平衡.趋向 通过下调Neuroligin1的表达或干扰其与PSD-95蛋白或Neurexin1β的相互作用,可间接抑制AMPA受体的功能,是未来疼痛治疗的研究方向.     

七氟醚抑制突触后胆碱能突触传递而不影响短时程增强

背景：目前人们已了解全身麻醉对兴奋性和抑制性突触的作用。但全身麻醉影响突触可塑性，从而影响学习和记忆的机制在细胞水平上尚不清晰。本研究选取体细胞一体细胞之间一致的突触后神经元，验证临床浓度的七氟醚是否影响胆碱能突触传递的短时程增强。     

全麻药突触前作用机制的研究进展

影响突触传递是大多数麻醉药的作用机制,近来其突触前效应逐渐引起重视.本文阐述了麻醉药对神经递质释放和调节分子机制的最新研究进展,为分析全麻药对突触传递的效应及完整地揭示麻醉药影响的突触传递机制提供了良好的基础.     

α-突触核蛋白寡聚化在认知障碍中的研究进展

α-突触核蛋白(α-synuclein,α-Syn)是一种高度丰富的突触前神经元蛋白。α-Syn的错误折叠和聚集与神经退行性疾病相关的认知损伤和术后神经认知功能障碍的发生有密切关系。文章就α-Syn寡聚体引发神经毒性的作用和在神经认知功能障碍的研究进展进行综述,较为系统地阐述其在认知功能障碍中的有害作用,为相关的疾病治疗干预开辟新的视角。     

胰腺癌侵袭和转移的分子生物学机制

胰腺癌是预后最差的消化系统恶性肿瘤 ,由于它的高侵袭性和高转移率 ,使近 80 %的患者无法获得根治性治疗。深入理解胰腺癌侵袭和转移的分子生物学机制 ,对于提高胰腺癌的疗效将起到重要的作用。一、细胞间黏附分子在侵袭和转移中的作用研究表明 ,细胞 -细胞和细胞 -基质间的黏附分子在胰腺癌的侵袭和转移中发挥重要作用。这些黏附分子包括类似于免疫球蛋白家族成员的细胞 -细胞间黏附分子、钙依赖性的钙黏蛋白家族和整合素 ,它们向细胞传递调节信号。细胞 -细胞间的黏附分子可阻止癌细胞侵入周围的基质 ,黏附作用的破坏将提高肿瘤细胞的运…     

Ezrin在肿瘤转移中的作用及机制研究进展

恶性肿瘤的远处转移是肿瘤治疗中的难点之一。Ezrin为膜细胞骨架连接蛋白,在多种恶性肿瘤中,Ezrin高表达与肿瘤转移密切相关,其通过改变肿瘤细胞极性及细胞运动、调节肿瘤细胞间黏附及细胞与细胞外基质黏附、参与肿瘤细胞内信号转导而影响恶性肿瘤转移。现对Ezrin在肿瘤转移中的作用、作用机制及其高表达分子调节机制的研究进展作一综述。     

Layer-specific expression of multiple cadherins in the developing visual cortex (V1) of the ferret

Cadherins are superfamily of Ca2+-dependent transmembrane glycoproteins with more than 100 members. They play a role in a wide variety of developmental mechanisms, including cell proliferation, cell differentiation, cell-cell recognition, neurite outgrowth and synaptogenesis. We cloned 16 novel members of the classic cadherin and delta-protocadherin subgroups from ferret brain. Their expression patterns were investigated by in situ hybridization in the developing primary visual cortex (V1) of the ferret. Fifteen out of the 16 cadherins are expressed in a spatiotemporally restricted fashion throughout development. Each layer of V1 can be characterized by the combinatorial expression of a subset of cadherins at any given developmental stage. A few cadherins are expressed by subsets of neurons in specific layers or by neurons dispersed throughout all cortical layers. Generally, the expression of protocadherins is more widespread, whereas that of classic cadherins is more restricted to specific layers. At the V1/V2 boundary, changes in layer-specific cadherin expression are observed. In conclusion, our results suggest that cadherins provide a code of potentially adhesive cues for layer formation in ferret V1. The persistence of expression in the adult suggests a functional role also in the mature cortex.     

促骨激素和生长因子对人骨髓基质细胞钙粘连素表达的调节

目的检测人骨髓基质细胞（hBMSCs）中钙粘连素是否连续表达，以及各种促骨激素和局部因子对其表达的调节。方法通过免疫定位和免疫印迹法检测原代hBMSCs和永生化骨母细胞系（hOP-7）中钙粘连素表达。结果钙粘连素表达与hOP-7细胞系的碱性磷酸酶（ALP）相关，多种促骨激素和局部因子对钙粘连素表达有调节作用。MoAb C-1821抗体阻断钙粘连素可增加ALP基础活性，并对1，25（OH）2D3诱导的ALP活性有增强作用。结论人骨母细胞中表达钙粘连素，并参与成骨分化。促骨因子对钙粘连素表达的差异性调节表明这些因子可以通过不同的钙     

The expression of cell adhesion molecules,cadherins: markers of kidney morphogenesis

Cadherins are protein molecules that promote cell adhesion in the presence of calcium. There are several classes of cadherins. The expression of two of these, namely the N- and E-cadherins, is intrinsically associated with the embryonic development of the kidney and thus their study provides a molecular basis for understanding the epithelial organization of this organ.     

Pan-cadherin as a high level phenotypic biomarker for prostate cancer

PURPOSE: High level phenotypic biomarkers such as cadherins are needed to identify individuals at risk for biologically active prostate cancer and determine which individuals with elevated prostate specific antigen or a prostate nodule are candidates for re-biopsy. Cadherins are a high level phenotypic biomarker associated with decreased cell adhesion, which is a cardinal event in carcinogenesis. Recently we reported that G-actin and tissue transglutaminase type II are potential biomarkers for prostate cancer. In this study we present cadherins as a potential third component of the biomarker profile. MATERIALS AND METHODS: Prostate tissues from 38 patients with cancer and 33 controls with a 10-year prostate cancer-free followup were labeled for pan-cadherin by immunohistochemical testing. Immunoreactivity was quantified using a Pathology Workstation (Autocyte Inc., Elon College, North Carolina). RESULTS: Visually benign glands from controls generally expressed cadherins, whereas regions of adenocarcinoma were generally negative. On quantitative immunohistochemistry 36 of 38 prostate cancer cases expressed a lower mean percent area positive for cadherin than the 19 benign prostatic hyperplasia and 14 prostatitis cases (odds ratio 978, 95% confidence interval 45 to 21,140, relative risk 18, 95% confidence interval 5 to 67, p <0.0001). Receiver operating characteristics analysis of immunohistochemical testing data showed that an optimal threshold of 7 produced 95% sensitivity and 100% specificity. CONCLUSIONS: Quantitative down-regulation of cadherin expression in prostate cancer tissue sections is a strong biomarker for prostate cancer. Analysis of cadherin and other high level phenotypic biomarker expression in the premalignant field may provide additional diagnostic information to decide which patients need re-biopsy, more intensive monitoring or chemoprevention.     

Hybrid GPCR/cadherin (Celsr) proteins in rat testis are expressed with cell type specificity and exhibit differential Sertoli cell-germ cell adhesion activity

Spermatogenesis requires Sertoli cell-germ cell adhesion for germ cell survival and maturation. Cadherins are a diverse superfamily of adhesion proteins; structurally unique members of this superfamily (celsr cadherins) are hybrid molecules containing extracellular cadherin repeats connected to a G protein-coupled receptor transmembrane motif. Here we demonstrate postnatal testicular mRNA expression of the 3 celsr paralogs (celsr1, celsr2, and celsr3), protein localization of celsr2 and celsr3, and functional analysis of celsr2 adhesion activity in primary Sertoli cell-germ cell co-cultures. Evaluation of celsr mRNA levels during a postnatal time course indicated that celsr1 and celsr2 were Sertoli cell and/or early-stage germ cell products, whereas celsr3 was expressed in later-stage germ cells. Cell type-specific expression was verified using the Sertoli cell line 93RS2, where celsr1 and celsr2 mRNA, but not celsr3, were detected. Immunostaining of testicular cryosections resulted in celsr2 protein localization to a spokelike pattern in the basal seminiferous epithelium and punctate figures in the apical epithelium, consistent with both Sertoli cell and germ cell expression. Celsr3 localized to punctate structures in the adluminal epithelium from postnatal day 40, consistent with elongate spermatid expression. The subcellular localization of celsr2 was examined further to define its localization in Sertoli cells and germ cells. Celsr2 localized to the Golgi complex in Sertoli cells and germ cells. In addition, germ cell celsr2 localized to a rab7-positive structure, which may be an endocytic compartment. Neither celsr2 nor celsr3 immunostaining was present at classic cadherin-based adhesion junctions. Nonetheless, the addition of a recombinant celsr2 protein fragment consisting of extracellular cadherin domains 4 through 8 to Sertoli cell-germ cell co-cultures resulted in germ cell detachment from Sertoli cells. Collectively, these data indicate that celsr cadherins have a cell type-specific expression pattern, and celsr2 may mediate Sertoli cell-germ cell adhesion outside of classic cadherin-based adhesion junctions.     

RNA结合基序蛋白3及其神经元保护作用

背景 RNA结合基序蛋白3(RNA binding motif protein 3,RBM3)是一种低温诱导产生的冷休克蛋白,可在神经元、部分胶质细胞和其他一些细胞系中表达.RBM3在多种神经元损伤中起到保护作用.目的 对RBM3的结构、功能和神经元保护作用等方面及相关研究进展进行综述.内容 概述RBM3的结构、表达和功能,阐述其在神经元保护方面的作用.趋向 对RBM3神经保护机制的研究为脑血管病变和心搏骤停患者损伤后的神经元复苏以及神经退行性疾病的治疗供新的方向.     

组蛋白去乙酰化酶对学习记忆的调控

背景 学习记忆行为是大脑的基本功能,揭示学习记忆的分子生物学机制有重要意义.近年来的研究发现,表观遗传修饰对学习记忆过程具有重要的调控作用,组蛋白乙酰化和去乙酰化是表观遗传修饰中最为常见的调节方式,乙酰化与去乙酰化平衡对学习记忆的正确形成与维持有极为重要的意义.去乙酰化由组蛋白去乙酰化酶(histone deacetylases,HDACs)调控.目的 阐述HDACs对学习记忆的调控作用及相关机制,为明确学习记忆的分子机制提供基础,并为学习记忆障碍治疗提供新思路.内容 HDACs的组织来源、分类、分子生物学功能.HDACs对学习记忆起负调控,使用其抑制剂可增强突触可塑性,改善受损的学习记忆.趋向 深入研究HDACs调控学习记忆的机制,不仅有助于阐明学习记忆及相关疾病的机制,并可为其治疗提供新靶点.     

Cadherin junctions in mammary tumors

Cadherins are the transmembrane component of adherens junctions found between interacting cells in tissues. The cadherins bind cells to one another in a specific manner and link to the actin cytoskeleton through intracellular catenins. In addition to promoting strong cell-cell adhesion, cadherins appear to initiate and modify intracellular signaling pathways. The loss of E-cadherin function in epithelial cells is thought to be an important step in tumorigenesis. Moreover, anomalous expression of inappropriate cadherins in epithelial cells alters their behavior and may contribute to the tumorigenic phenotype. For breast cancer the decreased expression of E-cadherin alone may have limited value as a prognostic indicator; however, examining the repertoire of cadherins and catenins expressed by tumors may provide useful prognostic information.     

TNF-alpha and IL-1beta suppress N-cadherin expression in MC3T3-E1 cells.

Excessive production of tumor necrosis factor (TNF) and interleukin-1 (IL-1) secondary to estrogen deficiency have been implicated as the cause of osteoporosis in postmenopausal woman. These cytokines appear to stimulate osteoclast precursor proliferation and activate mature osteoclast formation directly and possibly indirectly via osteoblasts. To investigate the other possible roles that these cytokines may play in stimulating the bone resorption process, we examined the effect of TNF-alpha and IL-1beta on cell-cell adhesion molecules, cadherins, in osteoblastic MC3T3-E1 cells. In this study, we investigated cadherin expression and the effect of TNF-alpha, IL-1beta, and parathyroid hormone (PTH) on the expression of cadherins in MC3T3-E1 cells. Confluent cultures of MC3T3-E1 cells were challenged with recombinant human TNF-alpha (1-100 U/ml), recombinant human IL-1beta (1-100 ng/ml) and human PTH(1-34) (1-100 ng/ml), respectively. The results show that MC3T3-E1 cells express functional cadherin molecules, N-cadherin and OB-cadherin. TNF-alpha (10-100 U/ml) and IL-1beta (10-100 ng/ml) suppressed N-cadherin without changing OB-cadherin expression, while PTH (1-100 ng/ml) had no effect on cadherin expression. These results raise the possibility that TNF-alpha and IL-1beta may compromise the cell-cell adhesion of osteoblasts which cover the bone surface. The ensuing compromised cell-cell adhesion of osteoblasts may in turn facilitate the direct adhesion of osteoclasts on the calcified bone matrix surface. These results implicate an indirect role for osteoblasts in the promotion of bone resorption by TNF-alpha and IL-1beta.     

Caspase-dependent cleavage of cadherins and catenins during osteoblast apoptosis.

As transmembrane, Ca2+-dependent cell-cell adhesion molecules, cadherins play a central role in tissue morphogenesis and homeostasis. Stable adhesion is dependent on interactions of the cytoplasmic domain of the cadherins with a group of intracellular proteins, the catenins. In the present study, we have detected the expression of alpha-, beta-, and gamma-catenins in human osteoblasts, which assemble with cadherins to form two distinct complexes containing cadherin and alpha-catenin, with either beta- or gamma-catenin. In osteoblasts undergoing apoptosis, proteolytic cleavage of N-cadherin and beta- and gamma- catenins but not alpha-catenin was associated with the activation of caspase-3 and prevented by the caspase inhibitor Z-VAD-fmk. The pattern of cadherin/catenin cleavage detected in apoptotic osteoblasts was reproduced in vitro by recombinant caspase-3. The presence of a 90-kDa extracellular domain fragment of N-cadherin in conditioned medium from apoptotic cells indicates that additional extracellular or membrane-associated proteases also are activated. Disruption of N-cadherin-mediated cell-cell adhesion with function-blocking antibodies induced osteoblast apoptosis, activation of caspases, and cleavage of beta-catenin. These findings provide compelling evidence that N-cadherin-mediated cell-cell adhesion promotes osteoblast survival and suggest that the underlying mechanism may involve activation of beta-catenin signaling.