REGIONAL MAPPING OF PRION PROTEINS IN BRAIN
REGIONAL MAPPING OF PRION PROTEINS IN BRAIN
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DOI：
10.1073/pnas.89.16.7620
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发表时间：
1992-08-15
影响因子：
11.1
通讯作者：
PRUSINER, SB
中科院分区：
文献类型：
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作者：
TARABOULOS, A;JENDROSKA, K;PRUSINER, SB
痒病的特征是朊蛋白PrP（Sc）的蛋白酶抗性异构体的积累。用有限的蛋白水解和混沌谱来绘制瘙痒病感染脑的低温切片中PrP（Sc）的分布，这些切片被涂在硝化纤维素膜上，称为组织块。为了在未感染的大脑中绘制朊病毒蛋白（PrP(C)）的细胞异构体，省略了蛋白水解。与免疫组化相比，组织块检测PrP（Sc）的灵敏度提高，PrP（Sc）积累模式不同。在患有Sc237痒病的叙利亚仓鼠中，最强烈的PrP（Sc）信号发生在PrP(C)相对较少的部位，这表明朊蛋白的异常定位可能是朊病毒疾病发病机制的一个重要特征。白质束PrP（Sc）免疫染色提示朊病毒沿神经解剖通路扩散。组织块中的PrP（Sc）免疫染色通过密度测定定量，允许评估特定结构内PrP（Sc）积累的程度。在克雅氏病和阿尔茨海默病患者的大脑中，组织切片也分别用于定位PrP（CJD）和β / a4 -淀粉样蛋白肽。
Scrapie is characterized by the accumulation of a protease-resistant isoform of the prion protein PrP(Sc). Limited proteolysis and chaotropes were used to map the distribution of PrP(Sc) in cryostat sections of scrapie-infected brain blotted onto nitrocellulose membranes, designated histoblots. Proteolysis was omitted in order to map the cellular isoform of the prion protein (PrP(C)) in uninfected brains. Compared with immunohistochemistry, histoblots increased the sensitivity for PrP(Sc) detection and showed different patterns of PrP(Sc) accumulation. In Syrian hamsters with Sc237 scrapie, the most intense PrP(Sc) signals occurred in sites with relatively little PrP(C), suggesting that aberrant localization of prion protein may be an important feature in the pathogenesis of prion diseases. Immunostaining of PrP(Sc) in white-matter tracts suggested that prions spread along neuroanatomical pathways. PrP(Sc) immunostaining in histoblots was quantitated by densitometry, permitting assessment of the extent of PrP(Sc) accumulation within specific structures. Histoblots were also useful in localizing PrP(CJD) and beta/A4-amyloid peptide in the brains of patients with Creutzfeldt-Jakob disease and Alzheimer disease, respectively.