Weber T, Aguzzi A
Neurologische Klinik, Marienkrankenhaus Hamburg, Deutschland.
Intervirology. 1997;40(2-3):198-212. doi: 10.1159/000150546.
Since the first description by A.M. Jakob and H.G. Creutzfeldt, five human diseases have been identified as transmissible spongiform encephalopathies (TSE). The disease bearing these authors' name, Creutzfeldt-Jakob disease (CJD) occurs sporadically, may be transmitted and has a genetic basis in 10-15% of all cases. Genetic diseases are the Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia. The latest form of CJD in humans, variant CJD (vCJD), was first described in 1996 and may be considered as evidence for a link between human TSEs and those in the animal kingdom. The putative agent of all TSEs is a proteinaceous infectious agent or prion. The gene for the physiological isoform of this protein (prion related protein or PrPc)-is encoded on the short arm of chromosome 20 in humans. The role of the physiological isoform of PrPc is unknown. The physiological isoform PrPc is protease-sensitive and thus designated as PrP-sen, while the pathological isoform is protease-resistant and thus called PrP-res. The pathological isoform PrP-res is invariably associated with TSEs and has given rise to the term prion diseases. PrP-sen and PrP-res have an identical amino acid sequence and have identical posttranslational modifications as assessed by currently available methodology but differ in their tertiary and quaternary structure. These structural differences are thought to be propagated by interaction of PrP-res with PrP-sen, appear to be governed by the polymorphism of PrPc and have been shown to be invariably associated with disease. PrP-sen has a high content of alpha-helical structures, PrP-res consists predominantly of beta-pleated sheets. These physicochemical characteristics of PrP-res cause it to behave like amyloid. The neuropathological hallmarks of TSEs or prion diseases are spongiform change, astrocytic gliosis, neuronal loss and PrP-positive plaques. A nucleic acid has never consistently been shown in any TSE. Diagnosis of TSE can be reliably made only postmortem.
自A.M. 雅各布（A.M. Jakob）和H.G. 克雅（H.G. Creutzfeldt）首次描述以来，已确定五种人类疾病为传染性海绵状脑病（TSE）。以这两位作者名字命名的疾病，即克雅氏病（CJD）呈散发性，可传播，且在所有病例中有10% - 15%具有遗传基础。遗传性疾病有格斯特曼 - 施特劳斯勒 - 申克综合征（Gerstmann - Sträussler - Scheinker syndrome）和致死性家族性失眠症。人类克雅氏病的最新形式，即变异型克雅氏病（vCJD），于1996年首次被描述，可被视为人类TSE与动物王国中TSE之间存在联系的证据。所有TSE的假定病原体是一种蛋白质感染因子或朊病毒。这种蛋白质（朊病毒相关蛋白或PrPc）的生理异构体的基因在人类20号染色体短臂上编码。PrPc生理异构体的作用尚不清楚。生理异构体PrPc对蛋白酶敏感，因此被称为PrP - sen，而病理异构体对蛋白酶具有抗性，因此被称为PrP - res。病理异构体PrP - res总是与TSE相关，并由此产生了朊病毒疾病这一术语。PrP - sen和PrP - res具有相同的氨基酸序列，并且根据目前可用的方法评估，它们具有相同的翻译后修饰，但它们的三级和四级结构不同。这些结构差异被认为是通过PrP - res与PrP - sen的相互作用而传播的，似乎受PrPc多态性的控制，并且已被证明总是与疾病相关。PrP - sen具有高含量的α - 螺旋结构，PrP - res主要由β - 折叠片组成。PrP - res的这些物理化学特性使其表现得像淀粉样蛋白。TSE或朊病毒疾病的神经病理学特征是海绵状改变、星形胶质细胞增生、神经元丧失和PrP阳性斑块。在任何TSE中从未始终如一地发现过核酸。TSE的诊断只能在死后可靠地做出。
