首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献，搜索用时 31 毫秒
1.
Mammalian prions are the infectious agents responsible for transmissible spongiform encephalopathies (TSE), a group of fatal, neurodegenerative diseases, affecting both domestic animals and humans. The most widely accepted view to date is that these agents lack a nucleic acid genome and consist primarily of PrP(Sc), a misfolded, aggregated form of the host-encoded cellular prion protein (PrP(C)) that propagates by autocatalytic conversion and accumulates mainly in the brain. The BSE epizooty, allied with the emergence of its human counterpart, variant CJD, has focused much attention on two characteristics that prions share with conventional infectious agents. First, the existence of multiple prion strains that impose, after inoculation in the same host, specific and stable phenotypic traits such as incubation period, molecular pattern of PrP(Sc) and neuropathology. Prion strains are thought to be enciphered within distinct PrP(Sc) conformers. Second, a transmission barrier exists that restricts the propagation of prions between different species. Here we discuss the possible situations resulting from the confrontation between species barrier and prion strain diversity, the molecular mechanisms involved and the potential of interspecies transmission of animal prions, including recently discovered forms of TSE in ruminants.  相似文献   

2.
Due to recent renewal of interest and concerns in prion diseases, a number of cell systems permissive to prion multiplication have been generated in the last years. These include established cell lines, neuronal stem cells and primary neuronal cultures. While most of these models are permissive to experimental, mouse-adapted strains of prions, the propagation of natural field isolates from sheep scrapie and chronic wasting disease has been recently achieved. These models have improved our knowledge on the molecular and cellular events controlling the conversion of the PrP(C) protein into abnormal isoforms and on the cell-to-cell spreading of prions. Infected cultured cells will also facilitate investigations on the molecular basis of strain identity and on the mechanisms that lead to neurodegeneration. The ongoing development of new cell models with improved characteristics will certainly be useful for a number of unanswered critical issues in the prion field.  相似文献   

3.
Scrapie and bovine spongiform encephalopathy are fatal neurodegenerative diseases caused by the accumulation of a misfolded protein (PrPres), the pathological form of the cellular prion protein (PrPC). For the last decades, prion research has greatly progressed, but many questions need to be solved about prion replication mechanisms, cell toxicity, differences in genetic susceptibility, species barrier or the nature of prion strains. These studies can be developed in murine models of transmissible spongiform encephalopathies, although development of cell models for prion replication and sample titration could reduce economic and timing costs and also serve for basic research and treatment testing. Some murine cell lines can replicate scrapie strains previously adapted in mice and very few show the toxic effects of prion accumulation. Brain cell primary cultures can be more accurate models but are difficult to develop in naturally susceptible species like humans or domestic ruminants. Stem cells can be differentiated into neuron‐like cells and be infected by prions. However, the use of embryo stem cells causes ethical problems in humans. Mesenchymal stem cells (MSCs) can be isolated from many adult tissues, including bone marrow, adipose tissue or even peripheral blood. These cells differentiate into neuronal cells, express PrPC and can be infected by prions in vitro. In addition, in the last years, these cells are being used to develop therapies for many diseases, including neurodegenerative diseases. We review here the use of cell models in prion research with a special interest in the potential use of MSCs.  相似文献   

4.
Faeces from infected animals have been suggested as a potential source of contamination and transmission of prion diseases in the environment. This work describes the development of a procedure for the detection of PrP(res) in stools which is based on a detergent-based extraction and immunoprecipitation (IP). The procedure was evaluated by analyzing TSE-spiked sheep and mice faeces, and proved to be specific for PrP(res) with sensitivities of 5-10mug of infected brain tissue. In order to analyze the shedding of prions, we studied stools from orally inoculated mice over 4-days post-inoculation and also stools from terminally sick scrapie-infected mice. PrP(res) was only detected in stools shortly after the oral ingestion of TSE agents. The procedure described could be a useful tool for studying the excretion of prions and for evaluating potential environmental contamination by prions.  相似文献   

5.
Generation of genuine prion infectivity by serial PMCA   总被引：2，自引：0，他引：2  
Prions are the causative infectious agents of transmissible spongiform encephalopathies (TSEs). They are thought to arise from misfolding and aggregation of the prion protein (PrP). In serial transmission protein misfolding cyclic amplification (sPMCA) experiments, newly formed misfolded and proteinase K-resistant PrP (PrPres) catalysed the structural conversion of cellular prion protein (PrP(C)) as efficiently as PrP(Sc) from the brain of scrapie-infected (263K) hamsters confirming an autocatalytic misfolding cascade as postulated by the prion hypothesis. However, the fact that PrPres generated in vitro was associated with approximately 10 times less infectivity than an equivalent quantity of brain-derived PrP(Sc) casts doubt on the "protein-only" hypothesis of prion propagation and backs theories that suggest there are additional molecular species of infectious PrP or other agent-associated factors. By combining sPMCA with prion delivery on suitable carrier particles we were able to resolve the apparent discrepancy between the amount of PrPres and infectivity which we were then able to relate to differences in the size distribution of PrP aggregates and consecutive differences in regard to biological clearance. These findings demonstrate that we have designed an experimental set-up yielding in vitro generated prions that are indistinguishable from prions isolated from scrapie-infected hamster brain in terms of proteinase K resistance, autocatalytic conversion activity, and - most notably - specific biological infectivity.  相似文献   

6.
The transmissible spongiform encephalopathies (TSEs) represent an emerging group of diseases that have been labeled as "prion diseases" because of the recent characterization of the infectious agent. TSEs are caused by prions, which induce neurodegenerative fatal diseases in humans and animals. Some TSEs (scrapie and kuru), have existed in both animals and humans for a very long time, whereas others such as bovine spongiform encephalopathy and variant Creutzfeld-Jakob disease have either recently emerged or are more thoroughly described and recognized. It is obvious that the medical community will be forced to consider these diseases in humans and animals for the future. This article offers a short review of the TSEs of immediate concern to zoo and wildlife veterinarians and wildlife biologists and suggests risk management strategies for the prevention of these diseases, with special focus on chronic wasting disease of cervids in North America.  相似文献   

7.
传染性海绵状脑病(transmissible spongiform encephalopathies,TSEs)是由朊病毒引起的人和多种哺乳动物以神经退行性变化为主要特征的一种慢性消耗性传染病,也称作朊病毒病;其是由体内正常细胞表面的PrPC转变成PrPSc蛋白所导致。但PrPSc主要在脑内表达,在其他组织表达量很低,因此快捷准确的诊断方法对于该病有重要意义。作者重点介绍以朊病毒的致病特点为依据建立的检测方法,便于对该疾病的早期诊断、预防以及食品安全检测提供帮助,保障畜牧业的有序发展以及人类的健康。  相似文献   

8.
In view of the first 64 BSE cases (date: 11.5.01) in German cattle herds an overview on TSE and their similarities and differences regarding clinic, pathogenesis and pathology is given. The mechanism of the unconventional agent, an infectious protein (prion), is explained based on the prion model of Stanley Prusiner. The knowledge on transmission, incubation time, host specificity as well as resistance and immunity drawn from experimentally infected animals is discussed. Thus, after oral infection prions are transported by lymphocytes from the stomach-intestinal tract to the spleen. The way to the CNS is still unknown. The presumption for crossing the species barrier is twofold: first the prions of different species have to be biochemically homologous and a genetical disposition has to exist. This is the case for BSE and the new variant of Creutzfeldt-Jakob-Disease (vCJD). There is evidence that in Great Britain so far 97 (date: 30.3.01) young people acquired vCJD due to consumption of food that contained bovine risk material. Regarding the infectious prion dosis brain, spinal cord and lymphoid tissues are regarded to be most dangerous. The principle of the BSE-test, its evidence as well as steps for prevention and control of BSE are presented.  相似文献   

9.
Synthetic prions     
The prion theory postulates that prions are novel infectious agents that are composed largely, if not entirely, of abnormally folded host-encoded prion proteins. However, the existence of different prion strains is enigma, if these novel infectious agents lack a genetic element, such as a nucleic acid. The best proof for this 'protein-only' concept would be the in vitro generation of prions from synthetic sources. Indeed, a substantial body of evidence has meanwhile been accumulated in favour of this postulate. This mini review recapitulates all relevant studies and experimental data on the generation of synthetic prions.  相似文献   

10.
Gap junctional intercellular communications (GJIC) contributes to neural function in development and differentiation of CNS. In this study, we have investigated the expression of GJIC during the differentiation of neuronal stem cells and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neuronal stem cell-derived cells from rat brain. During neuronal stem cell differentiation, expressions of Cx43 and 32 were increased for the duration of 72 hr, however the effect were decreased on the 7d. In the neuronal stem cell-derived cells, pretreatments with p38 MAP kinase inhibitor, SB203580, and MEK inhibitor, PD98059, could protect GJIC against TPA-induced inhibition of GJIC. Our data suggest that GJIC plays an important role during neuronal stem cell differentiation, and ERK1/2 and p38 MAP kinase signaling pathway may be closely related functionally to regulate gap junction in rat neuronal stem cell-derived cells.  相似文献   

11.
Synthetic Prions     
The prion theory postulates that prions are novel infectious agents that are composed largely, if not entirely, of abnormally folded host‐encoded prion proteins. However, the existence of different prion strains is enigma, if these novel infectious agents lack a genetic element, such as a nucleic acid. The best proof for this ‘protein‐only’ concept would be the in vitro generation of prions from synthetic sources. Indeed, a substantial body of evidence has meanwhile been accumulated in favour of this postulate. This mini review recapitulates all relevant studies and experimental data on the generation of synthetic prions.  相似文献   

12.
Liquid chip technology is a novel biomolecular detection technology which integrates laser technology,flow cytometry,digital signal processing and traditional chemical technology.It is widely used in various immunological analysis and nucleic acid detection.Single and mutiplex analysis are supported,with protein and nucleic acid targets detected in a variety of detection methods in high throughput manner.It has advantages of high throughput,easy operation,wide range of application,good repeatability,high specificity,less sample needed,high sensitivity and stablility,and low cost.Therefore,they are gradually replacing the traditional detection and quantitative pathogen methods,such as Real-time fluorescent quantitative nucleic acid amplification detection system (qPCR),enzyme-linked immunosorbent assay (ELISA) and other detection methods.Animal infectious diseases seriously endanger the development of the breeding industry,futhermore,some zoonoses such as highly pathogenic avian influenza also pose a serious threat to human health.An efficient and sensitive diagnostic system will help to screen a large number of samples during the outbreak of infectious diseases and prevent the spread of infection.The development of liquid chip technology provides a new platform for high-throughput detection and disease prevention.In this review,the principle and advantages of liquid chip technology are briefly described.The research progress of liquid chip technology in the detection of animal infectious diseases,including pigs diseases,poultry diseases,rabbit diseases,dog diseases,rodent diseases and other animal infectious diseases are summarized.We believe that in the future,this technology will become an important analytical and testing tool in clinical diagnosis,basic research,new drug development,judicial identification,food health supervision,biological weapons prevention and other fields.The development of this technology will greatly promote the research and development of life science.  相似文献   

13.
液相芯片技术是整合了激光技术、流式细胞仪、数字信号处理和传统化学技术的一种新型生物分子检测技术,目前广泛应用于各种免疫分析和核酸检测中。液相芯片技术支持单重和多重分析,可在多种测定方法中对蛋白质和核酸靶标进行高通量检测,具有高通量、操作简单、适用范围广、重复性好、特异性高、所需样品量少、更灵敏稳定、成本低等优点,正逐渐代替传统检测和定量病原体的工具,如实时荧光定量PCR扩增检测系统（qPCR）、酶联免疫吸附试验（ELISA）等检测方法。动物传染病严重危害着养殖业健康发展,一些诸如高致病性禽流感的人畜共患病对人类健康造成了严重威胁。高效灵敏的诊断系统将有助于在传染病暴发期间筛选大量样本,防止感染扩散。液相芯片技术的发展为高通量检测和疾病的预防提供了新的平台。作者简要概述了液相芯片技术的原理和优点,重点阐述了液相芯片技术在检测动物疫病,包括猪病、禽病、兔病、犬病、啮齿类动物和其他动物疫病方面的研究进展。相信今后液相芯片技术会成为临床诊断、基础研究、新药开发、司法鉴定、食品卫生监督、生物武器防范等领域的一项重要分析检测技术,该技术的发展将大大推动生命科学研究与进步。  相似文献   

14.
Niemann-Pick type C disease (NP-C) is a rare and ultimately fatal lysosomal storage disorder with variable neurologic symptoms. Loss of neuronal function and neuronal cell death occur in the NP-C brain, similar to the findings for other neurodegenerative diseases. Targeting of neuronal cells in the brain therefore represents a potential clinical intervention strategy to reduce the rate of disease progression and improve the quality of life. We previously reported that bone marrow stem cells show a neurogenic effect through CCL2 (also known as monocyte chemoattractant protein-1, MCP-1) secretion in the brains of NP-C mice. However, the direct effect of CCL2 on neurogenesis has not been ascertained. Here, to define neurogenic effects of CCL2 in NP-C, we applied human recombinant CCL2 to neural stem cells (NSCs) derived from NP-C mice. CCL2-treated NSCs showed significantly increased capacity for self-renewal, proliferation and neuronal differentiation. Similar results were observed in the subventricular zone of NP-C mice after CCL2 treatment. Furthermore, infusion of CCL2 into the NP-C mouse brain resulted in reduction of neuroinflammation. Taken together, our results demonstrate that CCL2 is a potential new therapeutic agent for NP-C.  相似文献   

15.
Nucleic acid probe technology is increasingly being used in basic research in veterinary microbiology and in diagnosis of infectious diseases of veterinary importance. This review presents an overview of nucleic acid probe methodology and its applications in veterinary infectious diseases. The major applications of nucleic acid probes include detection of pathogens in clinical samples, especially those organisms which are fastidious and difficult to cultivate, differentiation of virulent from avirulent organisms and vaccine strains from wild type isolates, typing of microorganisms, mapping genes, screening libraries of cloned DNA for specific genes, detection of latently infected or carrier animals, study of mechanisms of pathogenesis, epidemiological studies and food safety.  相似文献   

16.
Histopathological examination of the central nervous system is essential for the confirmation of a TSE diagnosis. Typical lesions are spongiform changes of the grey matter, intraneuronal vacuoles in particular nuclei of the brain stem, gliosis and neuronal degeneration. The nature of the lesions is similar between species. However, the variation in the distribution and severity of the changes is striking. Even more reliable than histopathology is the detection of disease-specific protease-resistant prion protein (PrPSc) using immunohistochemistry. The so-called "rapid tests" allow detection of PrPSc in unfixed tissues and are mostly used for the screening of risk populations and slaughtered animals.  相似文献   

17.
Transmissible spongiform encephalopathies are degenerative disorders affecting the central nervous system (CNS) occurring in a variety of species. The causative agent is thought to be composed of an abnormal form of the host encoded prion protein (PrPC), termed PrPSc. The conformational change of PrPC into PrPSc can occur spontaneously, however, it can also be induced by PrPSc. Prion diseases such as bovine spongiform encephalopathy (BSE), scrapie and variant Creutzfeldt-Jakob-Disease (vCJD) are most likely caused by peripheral uptake of prions. The process by which prions proceed to the CNS following peripheral uptake is referred to as neuroinvasion. Infection with prions is thought to occur in two phases: After ingestion prions first replicate in lymphatic tissue and then gain access to the CNS via peripheral nerves. Studies looking at the biochemical and clinical characteristics of BSE and vCJD demonstrated that BSE is most likely responsible for vCJD in humans.  相似文献   

18.
The protease-resistant infectious prion protein, PrPres, that causes transmissible spongiform encephalopathies, is remarkably resistant to conventional physical and chemical sterilization methods, including heat. It was hypothesized that thermal-dependent PrPres degradation has been underestimated, and the effect of prolonged incubation at 37 degrees C, 55 degrees C, and 80 degrees C on PrPres detection was examined using brain homogenates from chronic wasting disease-affected elk and mule deer (PrPCWD). Immunoblotting demonstrated progressive loss of PrPCWD immunoreactivity with time in all incubated samples as temperature increased, and PrPCWD was virtually undetectable after 90 days of incubation at 55 degrees C and 80 degrees C. These results indicate that decontamination methods and tissue disposal systems maintaining elevated temperatures for long periods of time could interfere with immunodetection, and the reliability of assays for PrPres detection could be compromised when applied to tissues exposed to heat with time. Although these results may suggest that such prolonged heat treatment could destroy prions, the observed loss of immunoreactivity does not necessarily correlate with a concurrent loss of infectivity. Bioassay is needed to determine if samples that have been incubated under these conditions retain infectivity.  相似文献   

19.
对抗菌药物具有强耐药性的“超级细菌”对人和家畜健康造成巨大威胁。广泛、高频使用种类有限的抗菌药物治疗人、家畜以及宠物细菌感染性疾病是产生“超级细菌”的根源。寻找现有常规抗菌药物的替代品或增强剂是当前热点研究方向之一。研究表明,间充质干细胞（mesenchymal stem cells,MSCs）具有抗菌特性。理论上,MSCs有可能成为治疗细菌感染性疾病的有效手段。对MSCs影响细菌存活的作用机制以及抗菌药物可能对MSCs功能产生的影响等方面的研究进展进行综述,以期为进一步阐明MSCs抗菌作用机制、挖掘MSCs作为治疗细菌感染性疾病新方法的潜力提供参考。  相似文献   

20.
A 5-day-old Japanese black calf was necropsied and intracytoplasmic vacuolations were histologically observed in many tissues. In the central nervous system, intracytoplasmic inclusions and vacuoles were found in neuronal cells. Intracytoplasmic inclusions were more conspicuous in the nuclei containing large nerve cells, especially in the brain stem and spinal cord. These inclusions were stained weak positive to positive with alcian blue, Giemsa, Luxol fast blue and periodic acid-Schiff stains but not with oil red O. Ultrastructurally, neuronal inclusions were observed in lysosomes and consisted of an amorphous electron-dense substance and occasional membranous structures. These findings seem to differ from the cases of bovine lysosomal diseases that have been reported, and this case may be another type of lysosomal storage disease.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号