Fornai F, Ferrucci M, Gesi M, Bandettini di Poggio A, Giorgi F S, Biagioni F, Paparelli A
Department of Human Morphology and Applied Biology, University of Pisa, via Roma 55, 56126 Pisa, Italy.
Brain Res Bull. 2006 Mar 31;69(2):95-100. doi: 10.1016/j.brainresbull.2005.12.005. Epub 2006 Jan 4.
Prion diseases include a group of either sporadic, inherited or infectious disorders characterized by spongiform neurodegeneration and reactive glyosis in several brain regions. Whatever the origin, the neuropathological hallmark of prion diseases is the presence of brain aggregates containing an altered isoform of a cellular protein, named prion protein. Recent findings show the potential toxicity of the normal cellular prion protein, which occurs when its physiological metabolism is altered. In particular, several studies demonstrate that accumulation of the prion protein in the cytosol can be a consequence of an increased amount of misfolded prion proteins, a derangement of the correct protein trafficking or a reduced activity of the ubiquitin-proteasome system. The same effects can be a consequence of a mutation in the gene coding for the prion protein. In all these conditions, one assists to accumulation and self-replication of insoluble prion proteins which leads to a severe disease resembling what observed following typical "prion infections". This article provides an opinion aimed at reconciling the classic Prusiner's theory concerning the "prion concepts" with the present knowledge arising from experimental studies on neurodegenerative disorders, suggesting a few overlapping steps in the pathogenesis of these diseases.
朊病毒病包括一组散发性、遗传性或传染性疾病，其特征是在几个脑区出现海绵状神经变性和反应性胶质增生。无论其起源如何，朊病毒病的神经病理学标志是存在含有细胞蛋白（称为朊病毒蛋白）异常异构体的脑内聚集体。最近的研究结果表明，正常细胞朊病毒蛋白在其生理代谢发生改变时具有潜在毒性。特别是，多项研究表明，朊病毒蛋白在细胞质中的积累可能是错误折叠的朊病毒蛋白数量增加、正确的蛋白质运输紊乱或泛素-蛋白酶体系统活性降低的结果。同样的影响也可能是编码朊病毒蛋白的基因突变的结果。在所有这些情况下，都会出现不溶性朊病毒蛋白的积累和自我复制，从而导致一种严重疾病，类似于典型“朊病毒感染”后观察到的情况。本文旨在调和经典的普鲁西纳关于“朊病毒概念”的理论与神经退行性疾病实验研究的现有知识，提出这些疾病发病机制中的一些重叠步骤。
