Prion Diseases: From Molecular Biology to Intervention Strategies
Prion Diseases: From Molecular Biology to Intervention Strategies
复制标题
朊病毒疾病：从分子生物学到干预策略
DOI：
10.1002/cbic.200300704
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发表时间：
2003
期刊：
影响因子：
3.2
通讯作者：
H. Schätzl
中科院分区：
文献类型：
--
作者：
Max Nunziante;S. Gilch;H. Schätzl
朊病毒病是致命的神经退行性感染性疾病，目前尚无治疗或预防方案。了解细胞朊病毒蛋白（PrPc）的构象转换成其病理亚型（PrPSc）的分子过程将是必要的，以制定有效的抗朊病毒策略。近年来，在PrPc的细胞生物学，在PrPSc的分子发病机制，并在这些情况下所涉及的细胞质量控制机制的新发现已经积累。已经描述了朊病毒蛋白在信号传导中的功能、蛋白酶体的可能影响以及作为细胞内废物沉积物的攻击体。在这里，重要的发病机制与更常见的神经退行性疾病的相似性是显而易见的。变异型克雅氏病（vCJD）的出现极大地说明了对治疗、暴露后和预防可能性的需要，这是一种由牛海绵状脑病（BSE）衍生的朊病毒引起的新的人类朊病毒疾病。虽然朊病毒在人类中的传染性通常仅限于中枢神经系统，但在vCJD患者中，朊病毒存在于淋巴网状系统中，理论上存在人与人之间意外传播的风险。在体外和基于细胞培养的测定或动物研究中，已经报道了多种化学抗朊病毒物质。偶尔，它们也进入了第一次人体试验。此外，在转基因模型中已经设计了各种有前途的干扰策略，尽管它们通常难以转移到非转基因体内情况。在外周朊病毒发病机制和免疫系统参与领域的新发现推动了以前被认为是完全不可能的抗朊病毒策略的研究。这为经典的免疫干扰技术打开了大门。值得注意的是，被动甚至主动的疫苗接种方法现在似乎是现实的目标。
Prion diseases are fatal neurodegenerative infectious disorders for which no therapeutic or prophylactic regimens exist. Understanding the molecular process of conformational conversion of the cellular prion protein (PrPc) into its pathological isoform (PrPSc) will be necessary to devise effective antiprion strategies. In recent years, new findings in the cell biology of PrPc, in the molecular pathogenesis of PrPSc, and in the cellular quality control mechanisms involved in these scenarios have accumulated. A function of the prion protein in signalling, the possible impact of the proteasome, and aggresomes as intracellular waste deposits have been described. Here, important pathogenetic similarities with the more frequent neurodegenerative disorders are evident. The need for therapeutic, postexposure, and prophylactic possibilities was drastically illustrated by the emergence of variant Creutzfeldt–Jakob disease (vCJD), a new human prion disease caused by bovine spongiform encephalopathy (BSE) derived prions. Although prion infectivity in humans is usually restricted to the central nervous system, in vCJD patients prions are present in the lympho‐reticular system, posing a theoretical risk of accidental human‐to‐human transmission. A variety of chemical antiprion substances have been reported in in vitro and cell culture based assays or in animal studies. Occasionally, they have also made their way into the first human trials. In addition, various promising interference strategies have been devised in transgenic models, although they are usually hard to transfer into nontransgenic in vivo situations. New findings in the fields of peripheral prion pathogenesis and immune system involvement fuelled the search for antiprion strategies formerly considered to be entirely impossible. This opened the door towards classical immunological interference techniques. Remarkably, passive and even active vaccination approaches now seem to be realistic goals.
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影响因子：
10.5
作者：
D. Westaway;V. Zuliani;C. Cooper;M. Da Costa;S. Neuman;A L Jenny;L. Detwiler;S. B. Prusiner
通讯作者：
D. Westaway;V. Zuliani;C. Cooper;M. Da Costa;S. Neuman;A L Jenny;L. Detwiler;S. B. Prusiner
DOI：
10.1073/pnas.90.8.3182
发表时间：
1993-04-15
影响因子：
11.1
作者：
ROGERS, M;YEHIELY, F;PRUSINER, SB
通讯作者：
PRUSINER, SB
影响因子：
3.3
作者：
Stewart, RS;Drisaldi, B;Harris, DA
通讯作者：
Harris, DA
受感染培养细胞细胞质囊泡中痒病朊病毒蛋白的超微结构定位。
DOI：
--
发表时间：
1991
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
McKinley,MP;Taraboulos,A;Kenaga,L;Serban,D;Stieber,A;DeArmond,SJ;Prusiner,SB;Gonatas,N
通讯作者：
Gonatas,N
影响因子：
56.9
作者：
Priola, SA;Raines, A;Caughey, WS
通讯作者：
Caughey, WS