Yale University Medical School, New Haven, CT, USA.
Virulence. 2013 Jul 1;4(5):373-83. doi: 10.4161/viru.24838. Epub 2013 Apr 30.
Transmissible encephalopathies (TSEs) are believed by many to arise by spontaneous conversion of host prion protein (PrP) into an infectious amyloid (PrP-res, PrP (Sc) ) without nucleic acid. Many TSE agents reside in the environment, with infection controlled by public health measures. These include the disappearance of kuru with the cessation of ritual cannibalism, the dramatic reduction of epidemic bovine encephalopathy (BSE) by removal of contaminated feed, and the lack of endemic scrapie in geographically isolated Australian sheep with susceptible PrP genotypes. While prion protein modeling has engendered an intense focus on common types of protein misfolding and amyloid formation in diverse organisms and diseases, the biological characteristics of infectious TSE agents, and their recognition by the host as foreign entities, raises several fundamental new directions for fruitful investigation such as: (1) unrecognized microbial agents in the environmental metagenome that may cause latent neurodegenerative disease, (2) the evolutionary social and protective functions of different amyloid proteins in diverse organisms from bacteria to mammals, and (3) amyloid formation as a beneficial innate immune response to stress (infectious and non-infectious). This innate process however, once initiated, can become unstoppable in accelerated neuronal aging.
传染性脑病（TSEs）被许多人认为是由宿主朊蛋白（PrP）自发转化为感染性淀粉样蛋白（PrP-res，PrP（Sc））而产生的，而无需核酸。许多 TSE 病原体存在于环境中，感染通过公共卫生措施得到控制。其中包括库鲁病随着食人仪式的停止而消失，受污染饲料的去除使牛海绵状脑病（BSE）的流行显著减少，以及具有易感 PrP 基因型的澳大利亚地理隔离绵羊中地方性羊瘙痒病的缺乏。虽然朊病毒蛋白模型引起了对不同生物体和疾病中常见类型的蛋白质错误折叠和淀粉样形成的强烈关注，但传染性 TSE 病原体的生物学特性及其被宿主识别为外来实体，为富有成效的研究提出了几个新的基本方向，例如：（1）环境宏基因组中可能导致潜伏神经退行性疾病的未被识别的微生物病原体，（2）不同生物体（从细菌到哺乳动物）中不同淀粉样蛋白的进化社会和保护功能，以及（3）淀粉样形成作为对压力（感染性和非感染性）的有益先天免疫反应。然而，这种先天过程一旦开始，在加速的神经元老化中就可能变得不可阻挡。
