A transmembrane form of the prion protein in neurodegenerative disease
A transmembrane form of the prion protein in neurodegenerative disease
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DOI：
10.1126/science.279.5352.827
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发表时间：
1998-02-06
期刊：
影响因子：
56.9
通讯作者：
Lingappa, VR
中科院分区：
文献类型：
--
作者：
Hegde, RS;Mastrianni, JA;Lingappa, VR
在内质网膜上，朊病毒蛋白（PrP）可以以几种拓扑形式合成。用表达PrP突变的转基因小鼠探索这些不同形式的作用，所述突变改变拓扑形式的相对比率，（称为（Ctm）PrP）在小鼠中产生类似于某些遗传性朊病毒疾病的神经退行性变化。来自这些小鼠的脑含有（Cim）PrP但不含有PrP（Sc），PrP同种型负责朊病毒疾病的传播。此外，在人类的一种可遗传的朊病毒疾病中，脑组织含有（Ctm）PrP但不含有PrP（Sc）。因此，内质网处蛋白质生物发生和拓扑学的异常调节可导致神经变性。
At the endoplasmic reticulum membrane, the prion protein (PrP) can be synthesized in several topological forms. The role of these different forms was explored with transgenic mice expressing PrP mutations that alter the relative ratios of the topological forms, Expression of a particular transmembrane form (termed (Ctm)PrP) produced neurodegenerative changes in mice similar to those of some genetic prion diseases, Brains from these mice contained (Cim)PrP but not PrP(Sc), the PrP isoform responsible for transmission of prion diseases, Furthermore, in one heritable prion disease of humans, brain tissue contained (Ctm)PrP but not PrP(Sc), Thus, aberrant regulation of protein biogenesis and topology at the endoplasmic reticulum can result in neurodegeneration.