Recent advances in the histo-molecular pathology of human prion disease
Recent advances in the histo-molecular pathology of human prion disease
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DOI：
10.1111/bpa.12695
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发表时间：
2019-03-01
期刊：
影响因子：
6.4
通讯作者：
Parchi, Piero
中科院分区：
文献类型：
--
作者：
Baiardi, Simone;Rossi, Marcello;Parchi, Piero
朊病毒疾病是影响人类和其他哺乳动物物种的进行性神经退行性疾病。术语朊病毒，最初提出的概念，提出一种蛋白质可能是传染性的，是指PrPSc，细胞朊病毒蛋白（PrPC）的错误折叠亚型，代表这些疾病的致病标志。发现其他蛋白质的特征是错误折叠和种子聚集可以从细胞传播到细胞，类似于PrPSc，增加了对朊病毒疾病的兴趣。然而，在神经退行性疾病中，朊病毒疾病因其更广泛的表型谱、最快的疾病进展和存在可通过摄入、注射或移植暴露于患病组织而传播的感染形式而与众不同。人类朊病毒病的主要临床病理表型包括迄今为止最常见的致命性失眠症克雅氏病、朊蛋白酶敏感性朊病毒病和Gerstmann-Straussler-Scheinker病。然而，临床病理表现甚至超出了这种分类的预测。由于它们的可传播性，朊病毒疾病的表型多样性也可以作为具有不同特征的朊病毒株传播到同基因宿主中，例如潜伏期、PrPSc分布模式和脑组织病理学变化的区域严重性。越来越多的证据表明，不同的PrPSc构象，形成不同的有序聚集体，加密相关的朊病毒株的表型变体。在这篇综述中，我们总结了最新的进展，有关人类朊病毒病的组织分子病理学的疾病的表型谱，包括共同病理学，朊病毒株的表征实验传输及其与PrPSc聚集体的理化性质的相关性。
Prion diseases are progressive neurodegenerative disorders affecting humans and other mammalian species. The term prion, originally put forward to propose the concept that a protein could be infectious, refers to PrPSc, a misfolded isoform of the cellular prion protein (PrPC) that represents the pathogenetic hallmark of these disorders. The discovery that other proteins characterized by misfolding and seeded aggregation can spread from cell to cell, similarly to PrPSc, has increased interest in prion diseases. Among neurodegenerative disorders, however, prion diseases distinguish themselves for the broader phenotypic spectrum, the fastest disease progression and the existence of infectious forms that can be transmitted through the exposure to diseased tissues via ingestion, injection or transplantation. The main clinicopathological phenotypes of human prion disease include Creutzfeldt-Jakob disease, by far the most common, fatal insomnia, variably protease-sensitive prionopathy, and Gerstmann-Straussler-Scheinker disease. However, clinicopathological manifestations extend even beyond those predicted by this classification. Because of their transmissibility, the phenotypic diversity of prion diseases can also be propagated into syngenic hosts as prion strains with distinct characteristics, such as incubation period, pattern of PrPSc distribution and regional severity of histopathological changes in the brain. Increasing evidence indicates that different PrPSc conformers, forming distinct ordered aggregates, encipher the phenotypic variants related to prion strains. In this review, we summarize the most recent advances concerning the histo-molecular pathology of human prion disease focusing on the phenotypic spectrum of the disease including co-pathologies, the characterization of prion strains by experimental transmission and their correlation with the physicochemical properties of PrPSc aggregates.