Cohen F E, Prusiner S B
Department of Biochemistry and Biophysics, University of California, San Francisco 94143, USA.
Annu Rev Biochem. 1998;67:793-819. doi: 10.1146/annurev.biochem.67.1.793.
While many aspects of prion disease biology are unorthodox, perhaps the most fundamental paradox is posed by the coexistence of inherited, sporadic, and infectious forms of these diseases. Sensible molecular mechanisms for prion propagation must explain all three forms of prion diseases in a manner that is compatible with the formidable array of experimental data derived from histopathological, biochemical, biophysical, human genetic, and transgenetic studies. In this review, we explore prion disease pathogenesis initially from the perspective of an autosomal dominant inherited disease. Subsequently, we examine how an intrinsically inherited disease could present in sporadic and infectious forms. Finally, we explore the phenomenologic constraints on models of prion replication with a specific emphasis on biophysical studies of prion protein structures.
尽管朊病毒疾病生物学的许多方面都不符合传统观念，但这些疾病的遗传性、散发性和传染性形式并存可能构成了最基本的矛盾。合理的朊病毒传播分子机制必须以一种与来自组织病理学、生物化学、生物物理学、人类遗传学和转基因研究的大量实验数据相一致的方式，解释朊病毒疾病的所有三种形式。在这篇综述中，我们首先从常染色体显性遗传病的角度探讨朊病毒疾病的发病机制。随后，我们研究一种内在遗传性疾病如何以散发性和传染性形式出现。最后，我们探讨朊病毒复制模型所受到的现象学限制，特别强调对朊病毒蛋白结构的生物物理学研究。
