"Protein-only" or "virino" in prion diseases?

60-year prion and scrapie research has led to a dilemma in understanding the unknown aetiology of the infectious neurodegenerative disorders with intriguing features. Current progress and dilemma in prion research are briefly but critically reviewed. Instead of providing a comprehensive coverage of the research history, attentions in this view are drawn toward both the major breakthrough in the advancement of protein-only hypothesis, and the puzzle why this hypothesis has not been fully accepted. In order to resolve the prion enigma in neuroscience, it is suggested that both technical and concept barriers remain to be crossed. Since prion research is a multi-interdisciplinary subject, this view is intended to both facilitate a better understanding of prion phenomenon by more scientists in natural science, and invite scientists outside the fields of molecular genetics and protein science for collaboration.     

"Protein-only" or "virino" in prion diseases?

60-year prion and scrapie research has led to a dilemma in understanding the unknown aetiology of the infectious neurodegenerative disorders with intriguing features. Current progress and dilemma in prion research are briefly but critically reviewed. Instead of providing a comprehensive coverage of the research history, attentions in this view are drawn toward both the major breakthrough in the advancement of protein-only hypothesis, and the puzzle why this hypothesis has not been fully accepted. In order to resolve the prion enigma in neuroscience, it is suggested that both technical and concept barriers remain to be crossed. Since prion research is a multi-interdisciplinary subject, this view is intended to both facilitate a better understanding of prion phenomenon by more scientists in natural science, and invite scientists outside the fields of molecular genetics and protein science for collaboration.     

朊病毒感染途径的研究进展

朊病毒病是一类能够感染人和其他动物的神经退行性传染病,其致死率高达100%,到目前为止尚无有效的治疗方法,该疾病直接威胁着人和动物的生命安全及健康。目前普遍认为该病的致病因子是一种结构异常的朊蛋白（PrPSc）,其主要入侵宿主的中枢神经系统,研究发现PrPSc主要通过消化系统、血液循环系统和外周神经系统途径进行复制并传播,然后进入中枢神经系统导致疾病发生。本文对PrPSc从外周组织器官入侵神经系统的途径进行综述,以理解朊病毒神经入侵的机制。     

Protein misfolding and disease: the case of prion disorders

Recent findings strongly support the hypothesis that diverse human disorders, including the most common neurodegenerative diseases, arise from misfolding and aggregation of an underlying protein. Despite the good evidence for the involvement of protein misfolding in disease pathogenesis, the mechanism by which protein conformational changes participate in the disease is still unclear. Among the best-studied diseases of this group are the transmissible spongiform encephalopathies or prion-related disorders, in which misfolding of the normal prion protein plays a key role in the disease. In this article we review recent data on the link between prion protein misfolding and the pathogensis of spongiform encephalopathies. Received 15 July 2002; received after revision 19 August 2002; accepted 23 August 2002 RID="*" ID="*"Corresponding author.     

病毒学对分子生物学发展的贡献

本文通过回顾病毒学发展史上的重大事件，尝试从以下几个方面说明病毒学的新发现对分子生物学发展所做出的贡献：①噬菌体感染实验和植物病毒重建实验证明了核酸是遗传信息的载体；②逆转录病毒的发现使人们认识到遗传信息的流动不是单向的；③逆转录酶已经成为基因克隆中重要的工具酶；④朊病毒的发现使人们认识到蛋白质很有可能成为核酸之外遗传信息的载体，扩展了人们对中心法则的认识；⑤各种野生型病毒被改造成为基因工程载体，广泛应用于基因工程．     

PrP<Superscript>c</Superscript> and reggies/flotillins are contained in and released via lipid-rich vesicles in Jurkat T cells

A new model of caveolin association with lipid body cores has recently been proposed which may be relevant to a number of cellular processes, e.g. lipid body generation. Here we show that PrP^c and reggie-1 and reggie-2 also occur in the cores of Nile Red/Bodipy-stained (neutral lipid-containing) vesicular structures and, in immunoblots, in the lipid-enriched fraction after density gradient centrifugation. These lipid-rich vesicles increase in number following cell feeding with oleic acid, differ from early endosome antigen 1- and Lamp-2-positive endosomes/lysosomes, exhibit an opaque content and lack surrounding actin staining. Our results suggest that the content of these vesicles, together with reggie-1 and -2 and PrP^c, is expelled.Received 3 May 2004; received after revision 14 June 2004; accepted 23 June 2004     

遗传密码的解析与生命公式的完善

作为遗传学发展中的重要事件,遗传密码的解析和遗传“中心法则”的完善经历了长时间的探索。通过梳理遗传密码发现、生命公式建立过程的历史史实,总结遗传密码的解析过程,还原生命公式从提出伊始时的线性结构发展到三角形结构的全过程。     

Evidence for oxidative damage to prion protein in prion diseases

In prion diseases the irreversible protein structural transformation process is completed in the brains of mammals within a few months, the uniformly generated infectivity displays extraordinary resistance to inactivation, suggesting that a vital energy source is required for the production of infectious particles. Considering the high oxygen-respiration rate in the brains, prion protein oxidative damage can be the crucial factor. Both theoretical consideration of the nature of protein radical reactions and a large body of previously unraveled feature of scrapie and prion diseases have provided multiple distinct lines of compelling evidence which persuasively support a suggestion that the infectious agents may be prion (free) radicals produced from protein oxidative damage. This paper describes that scrapie prions are most likely formed from prion radicals and oxidative species-mediated sequence-specific cross-linking of benign prion proteins.     

Scavenger, transducer, RNA chaperone? What ligands of the prion protein teach us about its function

Prion protein, a misfolded isoform of which is the essential component of the agent of prion diseases, still remains an enigmatic protein whose physiological functions are at best hypothetical. To gain a better insight into its putative role, many studies were undertaken to look for molecules that bind prion protein, and have notably identified divalent metal ions, several proteins, and nucleic acids. At first sight, the diversity of prion protein’s ligands seems of little help to infer a plausible function. However, the intrinsically disordered property of its N-terminal tail and the potential of the protein to adopt a transmembrane topology, can both be taken into account to predict its different states during its cellular cycle and its possible functions, of which the most promising correspond to a general scavenger, a sensor or adaptor in a signaling cascade, and an RNA chaperone. Received 16 August 2006; received after revision 7 November 2006; accepted 13 December 2006     

Investigating metal-binding in proteins by nuclear magnetic resonance

Metal ions play a key role for the function of many proteins. The interaction of the metal ion with the protein and its involvement in the function of the protein vary widely. In some proteins, the metal ion is bound tightly to the ligand residues and may be the key player in the function of the protein, as in the case of blue copper proteins. In other proteins, the metal ion is bound only temporarily and loosely to the protein, as in the case of some metalloenzymes and other proteins where the metal ion acts as a cofactor necessary for the function of the protein. Such proteins are often known as metal ion-activated proteins. The review focuses on recent nuclear magnetic resonance (NMR) studies of a series of metal-dependent proteins and the characterization of the metal-binding sites. In particular, we focus on NMR techniques for studying metal binding to proteins such as chemical shift mapping, paramagnetic NMR and changes in backbone dynamics upon metal binding. Received 12 October 2006; received after revision 30 November 2006; accepted 5 February 2007