The prion agent is unique in biology and is comprised of prion protein scrapie (PrPSc), a self-templating conformational variant of the host encoded prion protein cellular (PrPC). The deposition patterns of PrPSc in the CNS can vary considerably from a diffuse synaptic pattern to large plaque-like aggregates. Alterations of PrPC posttranslational processing can change PrPSc deposition patterns; however, the mechanism underlying these observations is unclear. In this issue of the JCI, Sevillano and authors determined that parenchymal PrPSc plaques of the mouse brain preferentially incorporated underglycosylated PrPC that had been liberated from the cell surface by the metalloproteinase, ADAM-10, in combination with heparan sulfate. These results provide mechanistic insight into the formation of PrPSc plaques and suggest that PrP posttranslational modifications direct pathogenicity as well as the rate of disease progression.

中文翻译：

---

糖基化程度低的朊病毒蛋白调节大脑中的斑块形成。

朊病毒剂在生物学中是独一无二的，由朊病毒蛋白痒病 (PrPSc) 组成，后者是宿主编码的朊病毒蛋白细胞 (PrPC) 的自模板构象变体。PrPSc 在 CNS 中的沉积模式可以有很大的不同，从弥漫性突触模式到大的斑块状聚集体。PrPC 翻译后加工的改变可以改变 PrPSc 沉积模式；然而，这些观察结果背后的机制尚不清楚。在本期 JCI 中，Sevillano 和作者确定小鼠大脑的实质 PrPSc 斑块优先掺入糖基化不足的 PrPC，后者已被金属蛋白酶 ADAM-10 与硫酸乙酰肝素结合从细胞表面释放出来。