Saá Paula, Harris David A, Cervenakova Larisa
Scientific Affairs,Holland Laboratory,American Red Cross,Rockville, MD,USA.
Department of Biochemistry,Boston University School of Medicine,Boston, MA,USA.
Expert Rev Mol Med. 2016 Apr 8;18:e5. doi: 10.1017/erm.2016.8.
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders characterised by long incubation period, short clinical duration, and transmissibility to susceptible species. Neuronal loss, spongiform changes, gliosis and the accumulation in the brain of the misfolded version of a membrane-bound cellular prion protein (PrP(C)), termed PrP(TSE), are diagnostic markers of these diseases. Compelling evidence links protein misfolding and its accumulation with neurodegenerative changes. Accordingly, several mechanisms of prion-mediated neurotoxicity have been proposed. In this paper, we provide an overview of the recent knowledge on the mechanisms of neuropathogenesis, the neurotoxic PrP species and the possible therapeutic approaches to treat these devastating disorders.
传染性海绵状脑病（TSEs），即朊病毒病，是致命的神经退行性疾病，其特征为潜伏期长、临床病程短，且可传播给易感物种。神经元丢失、海绵状改变、胶质细胞增生以及大脑中一种名为PrP（TSE）的膜结合细胞朊蛋白（PrP（C））错误折叠形式的积累，是这些疾病的诊断标志物。有力证据表明蛋白质错误折叠及其积累与神经退行性变化有关。因此，已经提出了几种朊病毒介导的神经毒性机制。在本文中，我们概述了关于神经病理发生机制、神经毒性PrP种类以及治疗这些毁灭性疾病的可能治疗方法的最新知识。
