Collins S J, Masters C L
Department of Clinical Neurosciences, St. Vincent's Hospital, Fitzroy, Melbourne, Australia.
Sci Prog. 1995;78 ( Pt 3):217-27.
The spongiform encephalopathies occur in both animals and humans, with kuru, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, and Fatal Familial Insomnia constituting the currently recognised spectrum of such disorders in man. All have proven to be transmissible, including familial cases. Important determinants of transmissibility include the route of inoculation (intracerebral is most effective) and the titre of the inoculated material (brain and spinal cord have greatest infectivity). However, in familial cases, the pathogenic mutations in the PrP gene additionally influence the efficacy of transmission. Recent progress in the molecular biological basis of these diseases suggests that most of the infectivity resides in an abnormal, relatively protease resistant, isoform of the constitutively expressed PrP. The abnormal isoform is postulated to serve as a template for auto-catalytic polymerisation and the consequent deposition of amyloid. Extensions of this hypothesis attempt to reconcile the paradox of how these disorders can be both infectious and also inherited in an autosomal dominant fashion.
海绵状脑病在动物和人类中均有发生，库鲁病、克雅氏病、格斯特曼综合征和家族性致死性失眠症构成了目前已知的人类此类疾病谱。所有这些疾病都已被证明具有传染性，包括家族性病例。传播的重要决定因素包括接种途径（脑内接种最为有效）和接种材料的滴度（脑和脊髓的传染性最强）。然而，在家族性病例中，朊蛋白（PrP）基因的致病性突变也会影响传播效率。这些疾病分子生物学基础方面的最新进展表明，大多数传染性存在于组成性表达的PrP的一种异常、相对抗蛋白酶的异构体中。据推测，这种异常异构体可作为自动催化聚合及随后淀粉样蛋白沉积的模板。对这一假说的拓展试图解释这些疾病如何既能具有传染性又能以常染色体显性方式遗传这一矛盾。
