MOLECULAR GENETICS OF SCRAPIE PATHOGENESIS

传染性海绵状脑病(TSE)是一组罕见的 包括绵羊瘙痒病在内的神经退行性疾病 年人患CJD和牛海绵状脑病(BSE) 牛群。TSE的感染体可以跨越物种障碍和 疯牛病在英国感染人类的可能性凸显 了解TSE发病机制的重要性。易感性 感染受正常宿主之间氨基酸同源性的影响 蛋白质(PrP-sen)及其异常的蛋白酶K抗性形式 蛋白质，PrP-Res。PrP-RES的形成与 传染性和对这种蛋白质如何形成的了解是至关重要的。 以了解TSE的发病机制并设计治疗方法 防止其合成的策略。我们的研究主要集中在 确定参与形成的PrP-Sen的结构区域 PrP-Res，描述PrP-Sen突变如何影响两者 PrP-Sen的特性和PrP-Res的形成效率， 以及PrP转录和/或翻译的变化如何导致 PrP蛋白的新形式。

Transmissible spongiform encephalopathies (TSE) are a group of rare neurodegenerative diseases including scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE) in cattle. The infectious agent of the TSE can cross species barriers and the likelihood that BSE has infected humans in Great Britain underscores the importance of understanding TSE pathogenesis. Susceptibility to infection is influenced by the amino acid homology between a normal host protein (PrP-sen) and the abnormal proteinase K-resistant form of this protein, PrP-res. Formation of PrP-res is closely associated with infectivity and an understanding of how this protein is made is critical for an understanding of TSE pathogenesis and for devising therapeutic strategies to prevent its synthesis. Our studies have focused on identifying the structural regions of PrP-sen involved in the formation of PrP-res, characterizing how mutations in PrP-sen can influence both the characteristics of PrP-sen and the efficiency of PrP-res formation, and how changes in transcription and/or translation of PrP can lead to novel forms of the PrP protein.