Piccardo P, Seiler C, Dlouhy S R, Young K, Farlow M R, Prelli F, Frangione B, Bugiani O, Tagliavini F, Ghetti B
Department of Pathology, Indiana University School of Medicine, Indianapolis 46202-5120, USA.
J Neuropathol Exp Neurol. 1996 Nov;55(11):1157-63. doi: 10.1097/00005072-199611000-00007.
Gerstmann-Sträussler-Scheinker (GSS) disease is a cerebral prion protein (PrP) amyloidosis associated with mutations in the PrP gene (PRNP). A GSS disease variant with mutation at codon 198 (F198S) has been studied in a large Indiana kindred. Biochemical investigations showed that the amyloid protein consists of 11 and 7 kDa fragments of PrP. Immunohistochemical studies showed that in addition to amyloid, these patients accumulate PrP deposits which are neither fluorescent nor birefringent when stained with thioflavin S and Congo red. In the present paper, we analyzed proteinase-K (PK)-resistant PrP in 7 patients with GSS F198S disease. Immunoblots of PK-treated brain extracts show prominent bands of ca. 27-29, 18-19, and 8 kDa. Immunohistochemistry and thioflavin-S-fluorescence show that the amyloid deposits are conspicuous in the cerebellum but sparse in the caudate nucleus. However, immunoblot analysis reveals PK-resistant PrP bands of similar intensity in both regions. Treatment with PK and PNGase F generates a pattern similar to that of PK alone. Our findings suggest that brain extracts from GSS F198S disease contain 3 prominent nonglycosylated PK-resistant PrP fragments forming a pattern not previously described in other prion diseases, which may in part explain the pathology of this GSS disease variant.
格斯特曼-施特劳斯勒-谢inker综合征（GSS）是一种与朊蛋白基因（PRNP）突变相关的脑朊蛋白（PrP）淀粉样变性病。在印第安纳州的一个大家族中对一种密码子198处发生突变（F198S）的GSS病变体进行了研究。生化研究表明，淀粉样蛋白由PrP的11 kDa和7 kDa片段组成。免疫组织化学研究表明，除淀粉样物质外，这些患者还积累了PrP沉积物，用硫黄素S和刚果红染色时既不发荧光也不具有双折射性。在本文中，我们分析了7例GSS F198S病患者中蛋白酶K（PK）抗性PrP。PK处理的脑提取物的免疫印迹显示出约27 - 29 kDa、18 - 19 kDa和8 kDa的明显条带。免疫组织化学和硫黄素S荧光显示，淀粉样沉积物在小脑中明显，但在尾状核中稀疏。然而，免疫印迹分析显示两个区域中PK抗性PrP条带的强度相似。用PK和PNGase F处理产生的模式与单独用PK处理相似。我们的研究结果表明，GSS F198S病患者的脑提取物含有3种突出的非糖基化PK抗性PrP片段，形成了一种在其他朊病毒疾病中未曾描述过的模式，这可能部分解释了这种GSS病变体的病理学特征。
