School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Republic of South Africa.
Prion. 2011 Jan-Mar;5(1):6-9. doi: 10.4161/pri.5.1.14283. Epub 2011 Jan 1.
Neurodegenerative diseases are caused by proteinaceous aggregates, usually consisting of misfolded proteins which are often typified by a high proportion of β-sheets, which accumulate in the Central Nervous System. These diseases, including Morbus Alzheimer, Parkinson disease and Transmissible Spongiform Encephalopathies (TSEs)--also termed prion disorders--afflict a substantial proportion of the human population and as such the etiology and pathogenesis of these diseases has been the focus of mounting research. Although many of these diseases arise from genetic mutations or are sporadic in nature, the possible horizontal transmissibility of neurodegenerative diseases poses a great threat to population health. In this article we discuss recent studies which suggest that the "non-transmissible" status bestowed upon Alzheimer and Parkinson diseases may need to be revised as these diseases have been successfully induced through tissue transplants. Furthermore, we highlight the importance of investigating the "natural" mechanism of prion transmission including peroral and perenteral transmission, proposed routes of gastrointestinal uptake and neuroinvasion of ingested infectious prion proteins. We examine the multitude of factors which may influence oral transmissibility and discuss the zoonotic threats which Chronic Wasting Disease (CWD), Bovine Spongiform Encephalopathy (BSE) and Scrapie may pose resulting in vCJD or related disorders. In addition, we suggest that the 37 kDa/67 kDa laminin receptor on the cell surface of enterocytes, a major cell population in the intestine, may play an important role in the intestinal pathophysiology of alimentary prion infections.
神经退行性疾病是由蛋白质聚集物引起的，通常由错误折叠的蛋白质组成，这些蛋白质通常具有较高比例的β-折叠，这些聚集物在中枢神经系统中积累。这些疾病包括阿尔茨海默病、帕金森病和传染性海绵状脑病（TSEs）——也称为朊病毒疾病——严重影响了相当一部分人口，因此这些疾病的病因和发病机制一直是研究的重点。尽管许多这些疾病是由基因突变引起的，或者是散发性的，但神经退行性疾病的可能横向传播对人口健康构成了巨大威胁。在本文中，我们讨论了最近的研究，这些研究表明，阿尔茨海默病和帕金森病的“非传染性”状态可能需要重新评估，因为这些疾病已经通过组织移植成功诱导。此外，我们强调了研究朊病毒传播的“自然”机制的重要性，包括经口和经肠传播、胃肠道摄取的可能途径以及摄入感染性朊病毒蛋白的神经入侵。我们研究了可能影响经口传播的多种因素，并讨论了慢性消耗性疾病（CWD）、牛海绵状脑病（BSE）和羊瘙痒病可能带来的人畜共患病威胁，从而导致变异型克雅氏病（vCJD）或相关疾病。此外，我们提出，肠上皮细胞表面的 37 kDa/67 kDa 层粘连蛋白受体可能在饮食性朊病毒感染的肠道病理生理学中发挥重要作用，肠上皮细胞是肠道中的主要细胞群体。
