Role of microglia and host prion protein in neurotoxicity of a prion protein fragment
Role of microglia and host prion protein in neurotoxicity of a prion protein fragment
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DOI：
10.1038/380345a0
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发表时间：
1996-03-28
期刊：
影响因子：
64.8
通讯作者：
Kretzschmar, HA
中科院分区：
文献类型：
--
作者：
Brown, DR;Schmidt, B;Kretzschmar, HA
朊病毒蛋白PrPc是一种功能未知的糖蛋白(1)，通常存在于神经元(2)和胶质细胞(3)中。它与牛海绵状脑病（BSE）、痒病和克雅氏病等疾病有关(4)。PrPSc是与疾病相关的PrPc的一种变异异构体，它表现出更强的蛋白酶抗性，并且是感染因子朊病毒的一部分（5,6）。朊病毒疾病的特征是神经元变性、胶质瘤和PrPSc的积累（参考文献7）。缺乏PrPc的小鼠对痒病有抵抗力(8)。由106-126氨基酸组成的人PrP片段在体外形成原纤维，对培养的神经元是有毒的（9-11）。在这里，我们发现这种毒性作用需要小胶质细胞的存在，这些小胶质细胞通过增加其氧自由基的产生来响应PrP106-126。PrP106-126的直接和小胶质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。
THE prion protein PrPc is a glycoprotein of unknown function(1) normally found in neurons(2) and glia(3). It is involved in diseases such as bovine spongiform encephalopathy (BSE), scrapie and Creutzfeldt-Jakob disease(4). PrPSc, an altered isoform of PrPc that is associated with disease, shows greater protease resistance and is part of the infectious agent, the prion(5,6). Prion diseases are characterized by neuronal degeneration, gliosis and accumulation of PrPSc (ref. 7). Mice devoid of PrPc are resistant to scrapie(8). A fragment of human PrP consisting of amino acids 106-126 that forms fibrils in vitro is toxic to cultured neurons(9-11). 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.