Prion感染的遗传学

虽然引起疯痒病和人类几种传染性神经衰退症的感染性Prion在许多方面类似于病毒,但分子和遗传分析表明Prion与病毒在结构和发病机制上有着基本的区别。在感染性Prion的制备过程中,鉴定出的唯一大分子物质是Prion蛋白的一种疾病特异性的同功体,且这种大分子物质是由寄主基因编码的。越来越多的资料支持这种论点,即Prion感染是一种新奇的宿主一病原物的相互作用。疯痒病是在绵羊和山羊中不易觉察的,自然发生的一种疾病,它导致中枢神经系统     

Prion名词的争议

Prion是protein和infection的缩写,是一种蛋白质侵染因子,引发致命性的脑病如人克雅病、疯牛病等,它与类病毒不同的是纯由蛋白质因子组成而不含有核酸。也就是说,尽管此病原不含核酸,但仅是蛋白质分子即可引发疾病,故称之为朊病毒（Prion）,它是一种科技创新的内含,这种蛋白质侵染因子（Prion）可被蛋白酶完全分解。Prion在我国最早音译叫普里昂,后科技名词委员会有关病毒学专家研究,将其译为朊病毒,而后多年引发争论不止。其实,普里昂和朊病毒均可,不用另立新词如朊粒等等。不过要特别提醒的是,不要把“朊”写成“肮”,在我国有些工具书如英汉生物学词典等将Prion译成中文名为肮病毒,朊与肮在汉字中是否通用,未做研究。     

建议将Prion译为朊病毒

建议将Ｐｒｉｏｎ译为朊病毒张友尚（中国科学院上海生物化学研究所，上海２０００３１）关键词Ｐｒｉｏｎ译名Ｐｒｉｏｎ是一类只有蛋白质没有核酸的病原体。它的发现对生物学的传统观念提出了挑战，因而在理论上具有重大意义。Ｐｒｉｏｎ引起的病变主要是蛋白质的淀粉样...     

Prion疾病疫苗研究策略

朊病毒病是一类侵袭人类及多种动物中枢神经系统的致死性退行性脑病,目前缺乏有效的预防和治疗方法。朊病毒病的重组蛋白亚单位疫苗、DNA疫苗、合成肽疫苗、病毒样颗粒疫苗、树突状细胞疫苗、黏膜免疫疫苗等已取得一定进展,但现有的免疫策略仅能部分克服免疫耐受,诱导较低或中等滴度的抗体,对PrPSc感染动物模型只能提供部分保护,Prion疫苗研究任重而道远。     

Prion special issue related to the III International Symposium on “The New Prion Biology

The year 2009 has been a crucial year for Prion, as our journal entered this year being listed in PubMedl Medline, Scopus and ISI databases. Our inclusion in these databases signifies recognition of Prion as a full fledged member of the community of the respected biomedical journals. This comes as a result of dedication and hard work of our publishers, editorial board members, authors and reviewers, who altogether made the very existence and timely functioning of Prion possible. Our thanks go to all of you, as well as to all our readers, whose needs and interests necessitate our existence, and to whom we sincerely hope to continue being useful and faithful.     

Prion Peptide Uptake in Microglial Cells – The Effect of Naturally Occurring Autoantibodies against Prion Protein

In prion disease, a profound microglial activation that precedes neurodegeneration has been observed in the CNS. It is still not fully elucidated whether microglial activation has beneficial effects in terms of prion clearance or whether microglial cells have a mainly detrimental function through the release of pro-inflammatory cytokines. To date, no disease-modifying therapy exists. Several immunization attempts have been performed as one therapeutic approach. Recently, naturally occurring autoantibodies against the prion protein (nAbs-PrP) have been detected. These autoantibodies are able to break down fibrils of the most commonly used mutant prion variant PrP106-126 A117V and prevent PrP106-126 A117V-induced toxicity in primary neurons. In this study, we examined the phagocytosis of the prion peptide PrP106-126 A117V by primary microglial cells and the effect of nAbs-PrP on microglia. nAbs-PrP considerably enhanced the uptake of PrP106-126 A117V without inducing an inflammatory response in microglial cells. PrP106-126 A117V uptake was at least partially mediated through scavenger receptors. Phagocytosis of PrP106-126 A117V with nAbs-PrP was inhibited by wortmannin, a potent phosphatidylinositol 3-kinase inhibitor, indicating a separate uptake mechanism for nAbs-PrP mediated phagocytosis. These data suggest the possible mechanisms of action of nAbs-PrP in prion disease.     

Prion: disease or relief?

The self-perpetuating amyloid isoform, or prion, of the yeast translation termination factor eRF3 modulates programmed translational frameshifting that controls a regulatory circuit determining the polyamine levels in a yeast cell. But it is still unclear whether this effect is adaptive or pathological.     

关于Prion汉译名的建议

关于Ｐｒｉｏｎ汉译名的建议贲昆龙张永振（中国科学院昆明动物研究所,昆明６５０２２３）关键词ｐｒｉｏｎ汉译名１９９７年的诺贝尔生理学与医学奖授予加利福尼亚大学旧金山分校的ＳｔａｎｌｅｙＢ．Ｐｒｕｓｉｎｅｒ,表彰他在研究传染性海绵状脑病变（ｔｒａｎｓｍｉ...     

对Prion译名的几点意见

80年代初,Prusiner等首先获得了部分纯化的搔痒病(scrapie)病原因子.其主要成份是一种蛋白质,未能证明它含核酸,故称之为"proteinaceous infectious particle",缩写为prion,以与普通病毒和类病毒相区分.Prusiner给这种病原因子所下的定义是:"不被大多数修饰核酸的方法灭活的蛋白质传染性颗粒"[1].     

Prion processing: a double-edged sword?

The events leading to the degradation of the endogenous PrP(C) (normal cellular prion protein) have been the subject of numerous studies. Two cleavage processes, α-cleavage and β-cleavage, are responsible for the main C- and N-terminal fragments produced from PrP(C). Both cleavage processes occur within the N-terminus of PrP(C), a region that is significant in terms of function. α-Cleavage, an enzymatic event that occurs at amino acid residues 110 and 111 on PrP(C), interferes with the conversion of PrP(C) into the prion disease-associated isoform, PrP(Sc) (abnormal disease-specific conformation of prion protein). This processing is seen as a positive event in terms of disease development. The study of β-cleavage has taken some surprising turns. β-Cleavage is brought about by ROS (reactive oxygen species). The C-terminal fragment produced, C2, may provide the seed for the abnormal conversion process, as it resembles in size the fragments isolated from prion-infected brains. There is, however, strong evidence that β-cleavage provides an essential process to reduce oxidative stress. β-Cleavage may act as a double-edged sword. By β-cleavage, PrP(C) may try to balance the ROS levels produced during prion infection, but the C2 produced may provide a PrP(Sc) seed that maintains the prion conversion process.     

Prion:1997诺贝尔生理学或医学奖

Ｐｒｉｏｎ：１９９７诺贝尔生理学或医学奖董昕王晓民韩济生（北京医科大学神经科学研究所,北京１０００８３）１９９７年正值阿尔弗雷德·诺贝尔（ＡｌｆｒｅｄＮｏｂｅｌ）逝世百年之际,瑞典卡罗琳斯卡研究院诺贝尔奖评选委员会将本年度诺贝尔生理学或医学奖授予美国...     

Prion疾病和“protein only”假说

Prion病是指一类由蛋白质错误折叠导致的具有传染性的疾病.人类的纹状体脊髓变性病、库鲁病、脑软化病,和致死的家族性失眠症以及动物的羊瘙痒病和牛海绵状脑炎即疯牛病,都是致死性的神经退行性疾病,它们都属于传染性海绵状脑炎,统称Prion病.PrP^C是Prion蛋白在细胞内的正常形式,PrP^Sc是其致病形式.根据“protein only”假说,PrP^C向PrP^Sc的转化是致病的关键步骤.简要介绍了PrP蛋白的结构特征、PrP^C向PrP^Sc转化的可能机制、影响PrP^C向PrP^Sc转化的重要因素和PrP在细胞内的生物学过程等方面的研究进展,讨论了Prion疾病的诊断和治疗方法.     

Prion protein gene polymorphisms in sheep in the state of Paraná, Brazil

To determine the polymorphisms of the prion protein gene in sheep from the state of Paraná, Brazil, 323 animals of meat breeds (Suffolk, Hampshire Down, Texel, Ile de France, Dorper, Dorset, Santa Inês and crossbreds) were genotyped by restriction fragment length polymorphism (RFLP) analysis. The most frequent allele was ARQ, with a frequency of 0.61, followed by ARR (0.30). VRQ and AHQ alleles were present at very low frequencies (0.13 and 0.05 respectively), and the ARH allele was not found. Seven genotypes were identified (ARR/ARR, ARR/ARQ, ARQ/ARQ, ARR/VRQ, ARR/AHQ, ARQ/VRQ and ARQ/AHQ), of which ARQ/ARQ was the most frequent (0.41). The Santa Inês breed and crossbred animals showed the highest genotypic variability.     

Prion蛋白寡聚化分子机制的研究进展

正朊病毒(prion)病是一类神经系统退行性疾病,是prion蛋白从正常态构象(PrP~C)转变为瘙痒态构象(PrP~(Sc))导致的。具有神经细胞毒性的可溶性prion蛋白寡聚体的形成是prion致病过程的重要步骤,其分子机制尚不清楚。林东海教授领导的课题组近年来对prion蛋白寡聚化进行研究,为阐明prion病发病机制和防治prion病提供有价值的信息。     

Prion infection: Seeded fibrillization or more?

The prion infection is a conversion of host encoded prion protein (PrP) from its cellular isoform PrP^C into the pathological and infectious isoform PrP^Sc; the conversion process was investigated by in vitro studies using recombinant and cellular PrP and natural PrP^Sc. We present a brief summary of the results determined with our in vitro conversion system and the derived mechanistic models. We describe well characterized intermediates and precursor states during the conversion process, kinetic studies of spontaneous and seeded fibrillogenesis and the impact of the membrane environment.Key words: prion protein conversion, seeding, fibril, dimer, precursor state, kinetics, membrane     

What Makes a Protein Sequence a Prion?

Typical amyloid diseases such as Alzheimer''s and Parkinson''s were thought to exclusively result from de novo aggregation, but recently it was shown that amyloids formed in one cell can cross-seed aggregation in other cells, following a prion-like mechanism. Despite the large experimental effort devoted to understanding the phenomenon of prion transmissibility, it is still poorly understood how this property is encoded in the primary sequence. In many cases, prion structural conversion is driven by the presence of relatively large glutamine/asparagine (Q/N) enriched segments. Several studies suggest that it is the amino acid composition of these regions rather than their specific sequence that accounts for their priogenicity. However, our analysis indicates that it is instead the presence and potency of specific short amyloid-prone sequences that occur within intrinsically disordered Q/N-rich regions that determine their prion behaviour, modulated by the structural and compositional context. This provides a basis for the accurate identification and evaluation of prion candidate sequences in proteomes in the context of a unified framework for amyloid formation and prion propagation.     

Prion hypothesis: the end of the controversy?

Forty-three years have passed since it was first proposed that a protein could be the sole component of the infectious agent responsible for the enigmatic prion diseases. Many discoveries have strongly supported the prion hypothesis, but only recently has this once heretical hypothesis been widely accepted by the scientific community. In the past 3 years, researchers have achieved the 'Holy Grail' demonstration that infectious material can be generated in vitro using completely defined components. These breakthroughs have proven that a misfolded protein is the active component of the infectious agent, and that propagation of the disease and its unique features depend on the self-replication of the infectious folding of the prion protein. In spite of these important discoveries, it remains unclear whether another molecule besides the misfolded prion protein might be an essential element of the infectious agent. Future research promises to reveal many more intriguing features about the rogue prions.