Priola S A, Raines A, Caughey W S
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Science. 2000 Feb 25;287(5457):1503-6. doi: 10.1126/science.287.5457.1503.
The transmissible spongiform encephalopathies (TSEs) are fatal, neurodegenerative diseases for which no effective treatments are available. The likelihood that a bovine form of TSE has crossed species barriers and infected humans underscores the urgent need to identify anti-TSE drugs. Certain cyclic tetrapyrroles (porphyrins and phthalocyanines) have recently been shown to inhibit the in vitro formation of PrP-res, a protease-resistant protein critical for TSE pathogenesis. We now report that treatment of TSE-infected animals with three such compounds increased survival time from 50 to 300%. The significant inhibition of TSE disease by structurally dissimilar tetrapyrroles identifies these compounds as anti-TSE drugs.
传染性海绵状脑病(TSEs)是致命的神经退行性疾病,目前尚无有效的治疗方法。牛型TSE跨越物种屏障并感染人类的可能性凸显了识别抗TSE药物的迫切需求。最近发现某些环状四吡咯(卟啉和酞菁)可在体外抑制PrP-res的形成,PrP-res是一种对TSE发病机制至关重要的蛋白酶抗性蛋白。我们现在报告,用三种此类化合物治疗TSE感染的动物可使存活时间延长50%至300%。结构不同的四吡咯对TSE疾病的显著抑制作用表明这些化合物可作为抗TSE药物。