蛋白质组学在阿尔采末病中的研究进展

蛋白质组学是基因组时代产生的一门重要学科,是从整体水平对蛋白质的综合分析。阿尔采末病（Alzheimer’s disease,AD）是常见而复杂的神经退行性疾病之一。应用蛋白质组学对AD进行研究,不仅可在蛋白质水平上揭示疾病的本质,还有助于全面探讨AD的病理机制,建立诊断标准,发现药物治疗靶点。本文从病理机制（特别是蛋白质翻译后修饰）、发现临床生物标签及治疗药物三个方面,对蛋白质组学在AD中的研究进展进行了综替。     

蛋白质组学在疾病研究中的应用

蛋白质组学是在蛋白质水平定量、动态、整体地研究生物体的一门学科。双向电泳技术、质谱技术和生物信息学是蛋白质组学的三大支撑技术。近年来,蛋白质组学技术从整体水平出发,在更贴近生命本质的层次上去发现和理解并应用于许多疾病的早期预警、诊断和治疗。我们对蛋白质组学在心血管疾病、肝病、胰腺疾病和自身免疫性疾病等研究中的应用做了简单阐述,揭示了蛋白质组学技术在许多重大疾病研究方面具有十分诱人的发展前景。     

蛋白质组学的应用研究进展

蛋白质组学(Proteomics)是一门大规模、高通量、系统化的研究某一类型细胞、组织或体液中的所有蛋白质组成及其功能的新兴学科。虽然基因决定蛋白质的水平,但是基因表达的水平并不能代表细胞内活性蛋白的水平,蛋白质组学分析是对蛋白质翻译和修饰水平等研究的一种补充,是全面了解基因组表达的一种必不可少的手段。蛋白质组学相关技术的发展极大地推动了蛋白质组学的研究进展,使其在各研究领域得到了广泛的应用。对蛋白质组学相关技术及其在各领域的应用进行了综述,最后对蛋白质组学的发展趋势和应用前景作出展望。     

血浆蛋白质组学的研究进展

血浆蛋白质组学是研究血浆蛋白质的功能和变化的一门科学。血浆中蕴藏着生命机体的所有信息,因此只有彻底了解血浆中存在哪些蛋白质,才能知道如何利用血浆来预测人体对疾病的易感性并监控疾病的进程,以期达到对疾病进行早诊断早治疗。由于血浆蛋白质组动态范围大,给研究带来了很大的困难。尤其是高丰度蛋白质的存在影响了低丰度蛋白质的检测率。而低丰度蛋白质都是有意义的具有临床诊断价值的蛋白质。因此去除高丰度蛋白质的干扰成了血浆蛋白质组学研究的关键。近年来,血浆蛋白质组学相关研究技术也得到了长足进展,为深入研究血浆蛋白质做出了重要贡献。血浆蛋白质组学作为一种无创性的研究方法,值得我们去探讨。本文就血浆蛋白质组学研究进展情况做一简要综述。     

蛋白质组学技术及其在心血管疾病研究中的应用

蛋白质组学是旨在研究蛋白质表达谱和蛋白质与蛋白质之间相互作用的新的领域。蛋白质组学的研究必须依赖高通量、自动化程度很高的技术。双向电泳、液相色谱和生物质谱技术的发展推动了蛋白质组学的研究。蛋白质组学为疾病发病机制的研究提供了新的思路和方法 ,本文重点介绍了蛋白质组学技术在心血管疾病研究中的应用     

蛋白质组学技术在病毒学研究中的应用

蛋白质组学是门研究细胞和组织中蛋白质的存在及其结构、翻译后修饰、表达水平,最终阐述蛋白质群体功能的学科[1],它不仅是对机体产生的所有蛋白进行系统分离解析,更重要的是对这些蛋白质如何行使功能作出解释.利用先进的蛋白质组学技术研究病毒及相闰关宿主蛋白的表达、翻译后修饰、定位、相互作用和功能进行系统研究,有助于深入了解病素毒复复制、与宿主相互作用以及引发疾病的机制。     

蛋白质组学在感染性疾病研究中的应用

蛋白质组学在人类疾病研究中的应用 ,主要是通过比较分析正常组织细胞与异常组织细胞、同一疾病在不同的发展时期细胞内整体蛋白质的表达差异 ,对差异表达的蛋白质进行鉴定、定量、表征 ,寻找与疾病相关的新的标志物 ,为人类疾病研究提供新的手段和依据 ,蛋白质组学在感染性疾病研究中的应用就是其中的一个方面。1 .蛋白质组学在感染性疾病研究中的应用蛋白质组学在人类感染性疾病研究中的应用主要是对引起感染性疾病的致病源的整体蛋白质进行研究 ,同时结合血清学 ,对其进行分析 ,鉴定出与疾病相关的新的标志物 ,为感染性疾病的诊断、治疗…     

军事医学科学院蛋白质组学研究进展

蛋白质组学是后基因组时代生命科学研究的热点和前沿领域.军事医学科学院是国内最早开展蛋白质组研究的单位之一,其蛋白质组学研究的发展不仅对中国蛋白质组研究起到重要的引领作用,也对国际蛋白质组学的发展做出了重要贡献.本文将重点介绍军事医学科学院的科学家在国际人类肝脏蛋白质组计划以及疾病蛋白质组、病原微生物蛋白质组等领域的研究成果.     

果蝇蛋白质组学研究进展

蛋白质组学旨在阐明基因组所表达的真正执行生命活动的全部蛋白质的表达规律和生物功能。随着人类基因组学计划的逐渐成熟,分子水平的实验技术不断发展,蛋白质组学的研究被提高到了前所未有的高度。果蝇是生命科学领域最为常用的一种模式生物,长期的系统研究也使果蝇的基因组成为至今注释最好的基因组之一,为功能基因组研究奠定了基础。但由于技术的限制,迄今有关果蝇蛋白质组学研究的报道尚不多见。近年来果蝇蛋白质组学的研究主要包括表达谱、修饰谱、比较蛋白质组学和疾病模型蛋白质组等四个方向,为进一步开展人类疾病临床蛋白质组学研究奠定了基础。     

蛋白质组学及其在肿瘤研究中的应用

简要介绍了蛋白质组学的概念、研究方法及其在肿瘤研究中的应用.蛋白质组学研究直接定位于蛋白质水平,从整体、动态、定量的角度去研究基因的功能,是后基因组计划的一个重要组成部分.恶性肿瘤是一种多基因参与的复杂疾病,从蛋白质整体水平上研究恶性肿瘤将有助于进一步揭示恶性肿瘤的发病机制,发现恶肿瘤特异性的标志物及其药物治疗的靶标.     

The cerebral proteopathies

The abnormal assembly and deposition of specific proteins in the brain is the probable cause of most neurodegenerative disease afflicting the elderly. These “cerebral proteopathies” include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), prion diseases, and a variety of other disorders. Evidence is accumulating that the anomalous aggregation of the proteins, and not a loss of protein function, is central to the pathogenesis of these diseases. Thus, therapeutic strategies that reduce the production, accumulation, or polymerization of pathogenic proteins might be applicable to a wide range of some of the most devastating diseases of old age.     

钙网蛋白与神经系统病变

钙网蛋白（calreticulin,CRT）是内质网中的一种多功能的分子伴侣,在协助蛋白质正确折叠和维持细胞Ca2＋稳态（Ca2＋信号）中发挥重要作用。近来的研究发现,钙网蛋白与神经系统病变包括阿尔茨海默氏病、帕金森病等有密切关系。     

The Role of Cyclophilins in Inflammatory Bowel Disease and Colorectal Cancer

Cyclophilins (Cyps) is a kind of ubiquitous protein family in organisms, which has biological functions such as promoting intracellular protein folding and participating in the pathological processes of inflammation and tumor. Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are two common intestinal diseases, but the etiology and pathogenesis of these two diseases are still unclear. IBD and CRC are closely associated, IBD has always been considered as one of the main risks of CRC. However, the role of Cyps in these two related intestinal diseases is rarely studied and reported. In this review, the expression of CypA, CypB and CypD in IBD, especially ulcerative colitis (UC), and CRC, their relationship with the development of these two intestinal diseases, as well as the possible pathogenesis, were briefly summarized, so as to provide modest reference for clinical researches and treatments in future.     

In vitro aggregation assays for the characterization of α-synuclein prion-like properties

Aggregation of α-synuclein plays a crucial role in the pathogenesis of synucleinopathies, a group of neurodegenerative diseases including Parkinson disease (PD), dementia with Lewy bodies (DLB), diffuse Lewy body disease (DLBD) and multiple system atrophy (MSA). The common feature of these diseases is a pathological deposition of protein aggregates, known as Lewy bodies (LBs) in the central nervous system. The major component of these aggregates is α-synuclein, a natively unfolded protein, which may undergo dramatic structural changes resulting in the formation of β-sheet rich assemblies. In vitro studies have shown that recombinant α-synuclein protein may polymerize into amyloidogenic fibrils resembling those found in LBs. These aggregates may be uptaken and propagated between cells in a prion-like manner. Here we present the mechanisms and kinetics of α-synuclein aggregation in vitro, as well as crucial factors affecting this process. We also describe how PD-linked α-synuclein mutations and some exogenous factors modulate in vitro aggregation. Furthermore, we present a current knowledge on the mechanisms by which extracellular aggregates may be internalized and propagated between cells, as well as the mechanisms of their toxicity.     

Small heat shock proteins protect against alpha-synuclein-induced toxicity and aggregation

Protein misfolding and inclusion formation are common events in neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD) or Huntington's disease (HD). Alpha-synuclein (aSyn) is the main protein component of inclusions called Lewy bodies (LB) which are pathognomic of PD, Dementia with Lewy bodies (DLB), and other diseases collectively known as LB diseases. Heat shock proteins (HSPs) are one class of the cellular quality control system that mediate protein folding, remodeling, and even disaggregation. Here, we investigated the role of the small heat shock proteins Hsp27 and alphaB-crystallin, in LB diseases. We demonstrate, via quantitative PCR, that Hsp27 messenger RNA levels are approximately 2-3-fold higher in DLB cases compared to control. We also show a corresponding increase in Hsp27 protein levels. Furthermore, we found that Hsp27 reduces aSyn-induced toxicity by approximately 80% in a culture model while alphaB-crystallin reduces toxicity by approximately 20%. In addition, intracellular inclusions were immunopositive for endogenous Hsp27, and overexpression of this protein reduced aSyn aggregation in a cell culture model.     

Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders

The common underlying feature of most neurodegenerative diseases such as Alzheimer disease (AD), prion diseases, Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) involves accumulation of misfolded proteins leading to initiation of endoplasmic reticulum (ER) stress and stimulation of the unfolded protein response (UPR). Additionally, ER stress more recently has been implicated in the pathogenesis of HIV-associated neurocognitive disorders (HAND). Autophagy plays an essential role in the clearance of aggregated toxic proteins and degradation of the damaged organelles. There is evidence that autophagy ameliorates ER stress by eliminating accumulated misfolded proteins. Both abnormal UPR and impaired autophagy have been implicated as a causative mechanism in the development of various neurodegenerative diseases. This review highlights recent advances in the field on the role of ER stress and autophagy in AD, prion diseases, PD, ALS and HAND with the involvement of key signaling pathways in these processes and implications for future development of therapeutic strategies.     

Protein misfolding in the late‐onset neurodegenerative diseases: Common themes and the unique case of amyotrophic lateral sclerosis

Enormous strides have been made in the last 100 years to extend human life expectancy and to combat the major infectious diseases. Today, the major challenges for medical science are age‐related diseases, including cancer, heart disease, lung disease, renal disease, and late‐onset neurodegenerative disease. Of these, only the neurodegenerative diseases represent a class of disease so poorly understood that no general strategies for prevention or treatment exist. These diseases, which include Alzheimer's disease, Parkinson's disease, Huntington's disease, the transmissible spongiform encephalopathies, and amyotrophic lateral sclerosis (ALS), are generally fatal and incurable. The first section of this review summarizes the diversity and common features of the late‐onset neurodegenerative diseases, with a particular focus on protein misfolding and aggregation—a recurring theme in the molecular pathology. The second section focuses on the particular case of ALS, a late‐onset neurodegenerative disease characterized by the death of central nervous system motor neurons, leading to paralysis and patient death. Of the 10% of ALS cases that show familial inheritance (familial ALS), the largest subset is caused by mutations in the SOD1 gene, encoding the Cu, Zn superoxide dismutase (SOD1). The unusual kinetic stability of SOD1 has provided a unique opportunity for detailed structural characterization of conformational states potentially involved in SOD1‐associated ALS. This review discusses past studies exploring the stability, folding, and misfolding behavior of SOD1, as well as the therapeutic possibilities of using detailed knowledge of misfolding pathways to target the molecular mechanisms underlying ALS and other neurodegenerative diseases. Proteins 2013; 81:1285–1303. © 2013 Wiley Periodicals, Inc.     

Physio-pathological roles of transglutaminase-catalyzed reactions

Transglutaminases (TGs) are a large family of related and ubiquitous enzymes that catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bi-substituted /crosslinked adducts) or -OH groups (to form ester linkages). In the absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. The TG enzymes are also capable of catalyzing other reactions important for cell viability. The distribution and the physiological roles of TG enzymes have been widely studied in numerous cell types and tissues and their roles in several diseases have begun to be identified. "Tissue" TG (TG2), a member of the TG family of enzymes, has definitely been shown to be involved in the molecular mechanisms responsible for a very widespread human pathology: i.e. celiac disease (CD). TG activity has also been hypothesized to be directly involved in the pathogenetic mechanisms responsible for several other human diseases, including neurodegenerative diseases, which are often associated with CD. Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, supranuclear palsy, Huntington's disease and other recently identified polyglutamine diseases, are characterized, in part, by aberrant cerebral TG activity and by increased cross-linked proteins in affected brains. In this review, we discuss the physio-pathological role of TG-catalyzed reactions, with particular interest in the molecular mechanisms that could involve these enzymes in the physio-pathological processes responsible for human neurodegenerative diseases.     

牛疾病相关基因的DNA变异及遗传控制

牛基因组中一些重要基因的DNA突变通过改变基因的表达和蛋白质功能来影响机体对疾病的抗性或易感性。控制牛疾病的DNA变异主要分为单基因座及多基因座两类。导致疾病的单基因座类型亦称因果突变,其遗传基础较简单,突变一般位于基因编码区或非编码区,多为单碱基或少数几个碱基的突变,这些突变导致氨基酸的错义突变、翻译提前终止或部分外显子缺失等。相比而言,多基因相关疾病的遗传基础较为复杂,遗传-病原体-环境间的互作是导致这类复杂疾病的主要原因。文章综述了由单基因座和多基因座遗传变异所控制的牛主要疾病的研究和应用现状,以及在牛育种及生产中为降低这些疾病的发生所采用的遗传控制策略。