Anchorless prion protein results in infectious amyloid disease without clinical scrapie
Anchorless prion protein results in infectious amyloid disease without clinical scrapie
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DOI：
10.1126/science.1110837
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发表时间：
2005-06-03
期刊：
影响因子：
56.9
通讯作者：
Oldstone, M
中科院分区：
文献类型：
--
作者：
Chesebro, B;Trifilo, M;Oldstone, M
在朊病毒和阿尔茨海默病中，淀粉样蛋白和非淀粉样蛋白沉积物在脑损伤中所起的作用仍然没有得到解决。在羊瘙痒病感染的转基因小鼠中，表达缺乏糖基磷脂酰肌醇（GPI）膜锚的朊蛋白（PrP），异常的蛋白酶抗性PrPres以淀粉样斑块的形式沉积，而不是通常的非淀粉样PrPres形式。虽然PrPres淀粉样蛋白斑块引起的脑损伤让人联想到阿尔茨海默病，但临床表现很小。相比之下，无锚和野生型PrP的联合表达产生加速的临床瘙痒症。因此，PrP GPI锚可能在朊病毒疾病的发病机制中发挥作用。
In prion and Alzheimer's diseases, the roles played by amyloid versus nonamyloid deposits in brain damage remain unresolved. In scrapie-infected transgenic mice expressing prion protein (PrP) lacking the glycosylphosphatidylinositol (GPI) membrane anchor, abnormal protease-resistant PrPres was deposited as amyloid plaques, rather than the usual nonamyloid form of PrPres. Although PrPres amyloid plaques induced brain damage reminiscent of Alzheimer's disease, clinical manifestations were minimal. In contrast, combined expression of anchorless and wild-type PrP produced accelerated clinical scrapie. Thus, the PrP GPI anchor may play a role in the pathogenesis of prion diseases.