核糖体蛋白S3a在肿瘤细胞增殖分化和凋亡调控作用的研究概况

目的综述核糖体蛋白S3a在肿瘤细胞增殖分化和凋亡调控作用的研究进展。方法参阅近几年国内外相关文献,对核糖体蛋白S3a的结构、功能及其异常表达对肿瘤细胞增殖分化和凋亡的调控等方面的进展进行归纳总结。结果与结论核糖体蛋白S3a除了在蛋白质合成中起重要作用外,还有独特的核糖体外功能。其在多种肿瘤细胞中高表达,通过调控癌基因和抑癌基因的表达可影响肿瘤细胞的增殖分化与凋亡。     

核糖体蛋白参与的核糖体生物合成在癌症中的研究

核糖体是由核糖核酸(RNA)和核糖体蛋白(RP)组装而成的大分子核糖核蛋白(RNP)复合物,在蛋白质生物合成中起关键作用。核糖体生物合成(RB)对调控细胞的呼吸至关重要,影响细胞的生长和增殖。本文主要以细胞质核糖体蛋白(CRP)和线粒体核糖体蛋白质(MRP)为切入点,介绍细胞内的核糖体生物合成过程,以及其在肿瘤发生发展中的异常调控。     

抗多药耐药靶点及相关药物的研究进展

抗多药耐药是指在疾病的治疗过程中,细胞对多种药物产生广泛的耐受,导致治疗效果不理想的现象。多药耐药多发于感染与肿瘤疾病的治疗中,已成为治愈这2类疾病的主要障碍。从转运蛋白和离子通道、酶以及核糖体这3个方面综述抗多药耐药靶点的机制及相关药物的研究进展,旨在为抗多药耐药药物的研发提供参考。     

核糖体展示小分子抗体的研究进展

核糖体展示技术是由Plückthun实验室[1]在多聚核糖体展示技术[2]的基础上改进而来的一种利用功能性蛋白相互作用进行筛选的新技术,它将正确折叠的蛋白及其mRNA同时结合在核糖体上,形成mRNA-核糖体-蛋白质三聚体,使目的蛋白的基因型和表型联系起来,可用于抗体及蛋白质文库选择、蛋白质体外改造等。运用此技术已成功筛选到一些与靶分子特异结合的高亲和力蛋白质,包括抗体、多肽、酶等,是蛋白质筛选的重要工具。1核糖体展示技术的基本原理及特点核糖体展示技术通过聚合酶链反应(PCR)扩增DNA文库,同时引入T7启动子、核糖体结合位点及茎-…     

靶向DNA损伤反应途径:PARP抑制剂抗肿瘤治疗研究进展

细胞在长期进化过程中形成的复杂的DNA损伤反应防御机制是维护基因组稳定性的重要途径,DNA损伤反应通路缺陷可导致包括肿瘤在内的多种疾病的发生。DNA损伤反应通路是一个复杂的信号通路,包括DNA损伤修复、凋亡、细胞周期调控等,DNA损伤反应通路已经成为新的抗肿瘤药物靶点。目前,已经开发多种DNA损伤反应通路相关的抑制剂,特别是对BRCA1和BRCA2基因突变的肿瘤,利用协同致死现象而开发的聚腺苷二磷酸核糖聚合酶抑制剂广泛应用于肿瘤个体化治疗。该文重点对DNA损伤反应通路抑制剂中的聚腺苷二磷酸核糖聚合酶抑制剂的作用分子机制、临床治疗、耐药性以及面临的挑战进行综述。     

心力衰竭的硝化应激和药物调治

在心力衰竭发病中涉及硝化应激、氧化增强和一氧化氮失调。过亚硝酸离子是反应性氧化剂，由一氧化氮与过氧化物阴离子反应生成，通过多种机制损害心血管功能，包括激活基质金属蛋白酶（MMP）和聚（ADP．核糖）聚合酶（PARP）。本文叙述了心力衰竭新的紧急治疗策略，即在这些病理生理条件下中和过亚硝酸离子，以及抑制MMP和PARP。     

克林霉素磷酸酯阴道凝胶刺激性试验

克林霉素磷酸酯为半合成抗生素 ,是林可霉素的衍生物。克林霉素磷酸酯在体外无效 ,在体内可以迅速转化成抗菌有效的克林霉素。克林霉素抑制细菌核糖和蛋白体的蛋白合成 ,其优先结合到 5 0s核糖体亚基影响肽链初始化过程。克林霉素体外对已经报道的与细菌性阴道炎有关的多数微生物菌株是一个活性抗菌剂。本品对细菌性阴道炎治愈率高且疗程短 ,局部用药治疗细菌性阴道炎可以避免和减少全身性用药的不良反应。本试验研究克林霉素磷酸酯阴道凝胶多次阴道给药后所产生的刺激反应 ,为临床安全用药提供参考。结果表明克林霉素磷酸酯阴道凝胶对大鼠…     

肺炎杆菌和肺炎球菌核糖体及核糖体蛋白的免疫原性

细菌核糖体的免疫效果已有很多报导,但产生免疫的有效成份尚未完全确定。作者为了深入研究肺炎杆菌和肺炎球菌核糖体制剂中蛋白质的免疫原作用,比较分析了粗制核糖体、用高浓度盐洗涤除去吸附蛋白质的核糖体,以及用嘌呤霉素处理除去新生多肽     

酸性核糖体磷酸化蛋白PO的研究进展

原核生物和真核生物的核糖体大亚基上都存在着一类与蛋白质翻译密切相关的酸性核糖体磷酸化蛋白。在真核生物它们是酸性核糖体磷酸化蛋白P0,P1,P2（acidic ribosomal phosphoproteins PO。P1andP2）,而在原核生物如Escheriehiacoli体内,它们分别为LIO和L7／L12蛋白．其中与P0蛋白相对应的蛋白为LIO,与P1、P2蛋白相对应的蛋白为L7／L12。原核生物和真核生物的酸性核糖体磷酸化蛋白在结构和功能上具有高度的同源性,所不同的是在原核生物,L7／L12蛋白是由同一基因编码的,     

PROTAC技术在神经退行性疾病中的研究进展

神经退行性疾病是指神经元系统功能或结构的进行性和选择性丧失，可导致认知和运动功能障碍，包括阿尔兹海默症、帕金森病、亨廷顿病及肌萎缩侧索硬化症等。目前，神经退行性疾病仍缺乏有效的治疗手段，亟待开发新型抗神经退行性疾病的药物。蛋白降解靶向嵌合体(PROTAC)是一种新兴的蛋白质降解技术，其在包括神经退行性疾病在内的多种疾病中显示出强大的应用潜力。本文作者聚焦神经退行性疾病相关的PROTAC分子，对其结构、降解活性及药效进行了概括总结，并分析了其应用前景以及面临的机遇和挑战。     

RPGR and RP2: targets for the treatment of X-linked retinitis pigmentosa?

Retinitis pigmentosa is the most important hereditary eye disease and there is currently no cure available. Although mutations were found in more than 40 genes in patients with retinitis pigmentosa, only two genes have thus far been found to be responsible for one of the most severe forms of the disease, X-linked retinitis pigmentosa. In this review, we highlight the current knowledge about the two gene products RPGR and RP2 and try to link genetic data from patients with functional data on the corresponding proteins. Based on the fact that recent gene therapeutic approaches for eye diseases are at a very promising stage, we discuss the potential of RPGR and RP2 as drug targets to treat retinitis pigmentosa.     

Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets

Members of the CCN family of matricellular proteins are crucial for embryonic development and have important roles in inflammation, wound healing and injury repair in adulthood. Deregulation of CCN protein expression or activities contributes to the pathobiology of various diseases - many of which may arise when inflammation or tissue injury becomes chronic - including fibrosis, atherosclerosis, arthritis and cancer, as well as diabetic nephropathy and retinopathy. Emerging studies indicate that targeting CCN protein expression or signalling pathways holds promise in the development of diagnostics and therapeutics for such diseases. This Review summarizes the biology of CCN proteins, their roles in various pathologies and their potential as therapeutic targets.     

Recent patents on Rho signaling pathway as therapeutic target for cardiovascular diseases

Rho protein represents a family of small GTP binding proteins that are involved in many important cellular functions including cell proliferation, migration and cytoskeletal reorganization. Rho protein is activated by GTP binding and is inactivated by hydrolyzing GTP to GDP. This process is influenced by variety of physiological and pathophysiological stimuli including growth factors, many vasoactive substances, smoking and mechanic stress or injury. Recent evidence suggest that targeting Rho protein per se or its downstream effector proteins such as Rho kinase or LIM kinase may have therapeutic potential in diseases such as hypertension, angina, myocardiac infarction (MI), atherosclerosis, tumor metastasis and spinal cord injury. Several recent patents have described modalities that regulate the activity of Rho, Rho kinase and LIM kinase as potential therapeutics. In this article, we will review the current knowledge on the cellular functions of Rho signaling pathway and strategies in targeting different components in Rho signaling pathway for human diseases with an emphasis on cardiovascular indications.     

RNA interference screening for the discovery of oncology targets

RNA interference (RNAi) mediated loss-of-function screens have the potential to delineate biological functions of genes and the proteins they encode. RNAi has proven to be a promising technology for identification and validation of new targets for the pharmacological treatment of many diseases including cancer. Here we review the use of high-throughput RNAi screens, examine the types of targets pursued for oncology indications, and discuss the integration of diverse datasets in both target discovery and drug discovery programs.     

Zn finger containing proteins as targets for the control of viral infections

The zinc finger proteins have fascinated many research groups because of their modular assembly, broad range of biological functions and more recently because they are attractive targets for antiviral therapy. The zinc finger domain is a very stable structural element whose hallmark is the coordination of a zinc ion by several amino acid residues, usually cysteines and histidines. These structural motifs are associated with protein-nucleic acid recognition as well as protein-protein interactions. The biological function of the zinc finger proteins is strongly dependent on the zinc ion, which assure integrity and stability. Thus, the disruption of critical zinc finger viral proteins represents a fundamentally new approach to inhibit viral replication in the absence of mutations leading to drug resistance phenotypes. This review summarizes the drug design and potential therapeutic applications of viral zinc fingers disrupting agents for the control of viral diseases.     

G protein-coupled receptors: novel targets for drug discovery in cancer

G protein-coupled receptors (GPCRs) belong to a superfamily of cell surface signalling proteins that have a pivotal role in many physiological functions and in multiple diseases, including the development of cancer and cancer metastasis. Current drugs that target GPCRs - many of which have excellent therapeutic benefits - are directed towards only a few GPCR members. Therefore, huge efforts are currently underway to develop new GPCR-based drugs, particularly for cancer. We review recent findings that present unexpected opportunities to interfere with major tumorigenic signals by manipulating GPCR-mediated pathways. We also discuss current data regarding novel GPCR targets that may provide promising opportunities for drug discovery in cancer prevention and treatment.     

Mitochondrial medicine: pharmacological targeting of mitochondria in disease

Mitochondria play a central role in cell life and death and are known to be important in a wide range of diseases including the cancer, diabetes, cardiovascular disease, and the age-related neurodegenerative diseases. The unique structural and functional characteristics of mitochondria enable the selective targeting of drugs designed to modulate the function of this organelle for therapeutic gain. This review discusses mitochondrial drug targeting strategies and a variety of novel mitochondrial drug targets including the electron transport chain, mitochondrial permeability transition, Bcl-2 family proteins and mitochondrial DNA. Mitochondrial drug-targeting strategies will open up avenues for manipulating mitochondrial functions and allow for selective protection or eradication of cells for therapeutic gain in a variety of diseases.     

Aptamers as therapeutics in cardiovascular diseases

With many advantages over other therapeutic agents such as monoclonal antibodies, aptamers have recently emerged as a novel and powerful class of ligands with excellent potential for diagnostic and therapeutic applications. Typically generated through Systematic Evolution of Ligands by EXponential enrichment (SELEX), aptamers have been selected against a wide range of targets such as proteins, phospholipids, sugars, nucleic acids, as well as whole cells. DNA/RNA aptamers are single-stranded DNA/RNA oligonucleotides (with a molecular weight of 5-40 kDa) that can fold into well-defined 3D structures and bind to their target molecules with high affinity and specificity. A number of strategies have been adopted to synthesize aptamers with enhanced in vitro/in vivo stability, aiming at potential therapeutic/diagnostic applications in the clinic. In cardiovascular diseases, aptamers can be developed into therapeutic agents as anti-thrombotics, anti-coagulants, among others. This review focuses on aptamers that were selected against various molecular targets involved in cardiovascular diseases: von Willebrand factor (vWF), thrombin, factor IX, phospholamban, P-selectin, platelet-derived growth factor, integrin α(v)β(3), CXCL10, vasopressin, among others. With continued effort in the development of aptamer-based therapeutics, aptamers will find their niches in cardiovascular diseases and significantly impact clinical patient management.     

Aggresome formation and neurodegenerative diseases: therapeutic implications

Accumulation of misfolded proteins in proteinaceous inclusions is a prominent pathological feature common to many age-related neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. In cultured cells, when the production of misfolded proteins exceeds the capacity of the chaperone refolding system and the ubiquitin-proteasome degradation pathway, misfolded proteins are actively transported to a cytoplasmic juxtanuclear structure called an aggresome. Aggresome formation is recognized as a cytoprotective response serving to sequester potentially toxic misfolded proteins and facilitate their clearance by autophagy. Recent evidence indicates that aggresome formation is mediated by dynein/dynactin-mediated microtubule-based transport of misfolded proteins to the centrosome and involves several regulators, including histone deacetylase 6, E3 ubiquitin-protein ligase parkin, deubiquitinating enzyme ataxin-3, and ubiquilin-1. Characterization of the molecular mechanisms underlying aggresome formation and its regulation has begun to provide promising therapeutic targets that may be relevant to neurodegenerative diseases. In this review, we provide an overview of the molecular machinery controlling aggresome formation and discuss potential useful compounds and intervention strategies for preventing or reducing the cytotoxicity of misfolded and aggregated proteins.