Piccardo P, Dlouhy S R, Lievens P M, Young K, Bird T D, Nochlin D, Dickson D W, Vinters H V, Zimmerman T R, Mackenzie I R, Kish S J, Ang L C, De Carli C, Pocchiari M, Brown P, Gibbs C J, Gajdusek D C, Bugiani O, Ironside J, Tagliavini F, Ghetti B
Indiana University School of Medicine, Indianapolis 46202-5120, USA.
J Neuropathol Exp Neurol. 1998 Oct;57(10):979-88. doi: 10.1097/00005072-199810000-00010.
Gerstmann-Sträussler-Scheinker disease (GSS), a cerebello-pyramidal syndrome associated with dementia and caused by mutations in the prion protein gene (PRNP), is phenotypically heterogeneous. The molecular mechanisms responsible for such heterogeneity are unknown. Since we hypothesize that prion protein (PrP) heterogeneity may be associated with clinico-pathologic heterogeneity, the aim of this study was to analyze PrP in several GSS variants. Among the pathologic phenotypes of GSS, we recognize those without and with marked spongiform degeneration. In the latter (i.e. a subset of GSS P102L patients) we observed 3 major proteinase-K resistant PrP (PrPres) isoforms of ca. 21-30 kDa, similar to those seen in Creutzfeldt-Jakob disease. In contrast, the 21-30 kDa isoforms were not prominent in GSS variants without spongiform changes, including GSS A117V, GSS D202N, GSS Q212P, GSS Q217R, and 2 cases of GSS P102L. This suggests that spongiform changes in GSS are related to the presence of high levels of these distinct 21-30 kDa isoforms. Variable amounts of smaller, distinct PrPres isoforms of ca. 7-15 kDa were seen in all GSS variants. This suggests that GSS is characterized by the presence PrP isoforms that can be partially cleaved to low molecular weight PrPres peptides.
格斯特曼-施特劳斯勒-谢inker病（GSS）是一种与痴呆相关的小脑-锥体综合征，由朊蛋白基因（PRNP）突变引起，其表型具有异质性。导致这种异质性的分子机制尚不清楚。由于我们推测朊蛋白（PrP）的异质性可能与临床病理异质性有关，本研究的目的是分析几种GSS变异体中的PrP。在GSS的病理表型中，我们识别出有无明显海绵状变性的情况。在后者（即GSS P102L患者的一个子集）中，我们观察到约21-30 kDa的3种主要蛋白酶K抗性PrP（PrPres）异构体，类似于在克雅氏病中看到的那些。相比之下，在没有海绵状改变的GSS变异体中，包括GSS A117V、GSS D202N、GSS Q212P、GSS Q217R以及2例GSS P102L中，21-30 kDa异构体并不突出。这表明GSS中的海绵状改变与这些不同的21-30 kDa异构体的高水平存在有关。在所有GSS变异体中都可见到可变数量的约7-15 kDa的较小的、不同的PrPres异构体。这表明GSS的特征是存在可部分切割为低分子量PrPres肽的PrP异构体。
