朊病毒:构象疾病的模型?

F. Morinet
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引用次数: 9

摘要

斯坦利·普鲁西纳在1980年左右发现一种蛋白质可以模仿病毒和细菌病原体,这是出乎意料的。现在有证据表明,克雅氏病和相关疾病是由朊病毒引起的。朊病毒和例如神经退行性疾病,产生于相同的一般疾病机制。在每一个细胞中,都有异常的蛋白质展开和聚集。与蛋白质错误折叠障碍发病机制相关的蛋白质构象变化产生富含β片的低聚物,这些低聚物部分抵抗蛋白质水解,并具有形成淀粉样聚集体的高倾向。区分朊病毒和淀粉样蛋白是很重要的:朊病毒不需要聚合成淀粉样蛋白原纤维,可以作为低聚物进行自我繁殖。朊病毒疾病的特征是PrPc向PrPsc的构象转化,PrPsc是朊病毒疾病的基本甚至潜在的基础。尽管朊病毒和传统的感染性微生物之间存在明显的差异,但朊病毒符合科赫的假设。有意义的治疗可能需要混合药物,以干扰前体向朊病毒的转化并增强对朊病毒的清除;这种方法可能在更常见的退行性疾病中得到应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prions: A model of conformational disease?

The discovery that a protein could mimic viral and bacterial pathogens around 1980 by Stanley Prusiner was unexpected. Evidence shows now that Creutzfeldt-Jakob disease and related disorders are caused by prions. Prions and, for example neurodegeneratives diseases, arise from the same general disease mechanism. In each, there is abnormal unfolding and then aggregation of proteins. The protein conformational changes associated with the pathogenesis of protein misfolding disorders produce β sheet rich oligomers that are partially resistant to proteolysis and have a high tendency to form amyloid-like aggregates. It is important to distinguish between prions and amyloids: prions need not to polymerize into amyloid fibrils and can undergo self-propagation as oligomers. The prion diseases are characterized by the conformational conversion of PrPc to PrPsc, the fundamental even underlying prion diseases. Despite the obvious differences between prions and conventional infectious microorganisms, prions fulfill the Koch's postulates. Meaningful treatments are likely to require cocktails of drugs that interfere with the conversion of precursor into prions and enhance the clearance of prions; such an approach may find application in the more common degenerative diseases.

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来源期刊
Pathologie-biologie
Pathologie-biologie 医学-病理学
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