Prion protein and species barriers in the transmissible spongiform encephalopathies
Prion protein and species barriers in the transmissible spongiform encephalopathies
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DOI：
10.1016/s0753-3322(99)80057-2
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发表时间：
1999-02-01
影响因子：
7.5
通讯作者：
Priola, SA
中科院分区：
文献类型：
--
作者：
Priola, SA
在传染性海绵状脑病（transmissible spongiform encephalopathies，TSE）中，正常蛋白酶敏感的宿主蛋白PrP-sen向异常蛋白酶抗性形式PrP-res的转化是疾病发病机制中的关键步骤。PrP-sen和PrP-res之间的氨基酸错配可以显著影响PrP-res的量，并调节对TSE感染性跨物种传播的抗性。在转基因小鼠，组织培养细胞，和无细胞系统的实验已被用来确定在PrP-res形成的重要PrP的区域。这些研究都表明，在PrP分子的中间三分之一的同源性是至关重要的物种特异性的PrP-res的形成。在这个区域内的多态性与仓鼠和一些山羊的抗瘙痒症和牛海绵状脑病（BSE），而在关键氨基酸残基的同源性可能有助于跨物种传播的BSE给人类。这些研究已被证明在理解TSE中物种屏障的分子基础以及PrP-res形成中涉及的重要二级结构方面非常宝贵。（C）1999 Elsevier，巴黎。
In the transmissible spongiform encephalopathies (TSE), the conversion of the normal protease-sensitive host protein PrP-sen to an abnormal protease-resistant form, PrP-res, is a critical step in disease pathogenesis. Amino acid mismatches between PrP-sen and PrP-res can dramatically affect the amount of PrP-res made and modulate the resistance to cross-species transmission of TSE infectivity. Experiments in transgenic mice, tissue culture cells, and cell-free systems have been used to identify the regions in PrP important in PrP-res formation. These studies have all shown that homology in the middle third of the PrP molecule is critical for the species-specific formation of PrP-res. Polymorphisms within this region correlate with the resistance of hamsters and some goats to scrapie and bovine spongiform encephalopathy (BSE) while homology at critical amino acid residues might facilitate cross-species transmission of BSE to humans. Studies such as these have proven invaluable in understanding the molecular basis of species barriers in the TSE as well as the important secondary structures involved in the formation of PrP-res. (C) 1999 Elsevier, Paris.