Brown D R, Schmidt B, Kretzschmar H A
Institut für Neuropathologie, Universität Göttingen, Germany.
Nature. 1996 Mar 28;380(6572):345-7. doi: 10.1038/380345a0.
The prion protein PrPc is a glycoprotein of unknown function normally found in neurons and glia. It is involved in diseases such as bovine spongiform encephalopathy (BSE), scrapie and Creutzfeldt-Jakob disease. PrPSc, an altered isoform of PrPC that is associated with disease, shows greater protease resistance and is part of the infectious agent, the prion. Prion diseases are characterized by neuronal degeneration, gliosis and accumulation of PrPSc. Mice devoid of PrPC are resistant to scrapie. A fragment of human PrP consisting of amino acids 106-126 that forms fibrils in vitro is toxic to cultured neurons. Here we show that this toxic effect requires the presence of microglia which respond to PrP106-126 by increasing their oxygen radical production. The combined direct and microglia-mediated effects of PrP106-126 are toxic to normal neurons but are insufficient to destroy neurons from mice not expressing PrPC.
朊病毒蛋白PrPc是一种功能未知的糖蛋白，通常存在于神经元和神经胶质细胞中。它与牛海绵状脑病（BSE）、羊瘙痒病和克雅氏病等疾病有关。PrPSc是与疾病相关的PrPC的一种改变的异构体，具有更高的蛋白酶抗性，是感染因子朊病毒的一部分。朊病毒疾病的特征是神经元变性、胶质细胞增生和PrPSc的积累。缺乏PrPC的小鼠对羊瘙痒病具有抗性。由氨基酸106 - 126组成的人PrP片段在体外形成纤维，对培养的神经元有毒性。在这里，我们表明这种毒性作用需要小胶质细胞的存在，小胶质细胞通过增加其氧自由基的产生来对PrP106 - 126作出反应。PrP106 - 126的直接作用和小胶质细胞介导的联合作用对正常神经元有毒性，但不足以破坏不表达PrPC的小鼠的神经元。
