Prion Strain Interactions Are Highly Selective
Prion Strain Interactions Are Highly Selective
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DOI：
10.1523/jneurosci.2417-10.2010
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发表时间：
2010-09-08
影响因子：
5.3
通讯作者：
Sigurdson, Christina J.
中科院分区：
文献类型：
--
作者：
Nilsson, K. Peter R.;Joshi-Barr, Shivanjali;Sigurdson, Christina J.
各种错误折叠和聚集的神经元蛋白通常在神经退行性疾病中共存，但这些蛋白是否共聚集并改变疾病的发病机制尚不清楚。在这里，我们使用不同的朊病毒株的混合物，这被认为是不同的构象，以测试的假设，两个不同的聚集体相互作用，并改变体内的疾病。我们跟踪两种朊病毒株在小鼠组织病理学和生物化学，以及通过光谱分析斑块结合的PTAA（聚噻吩乙酸），构象敏感的荧光淀粉样蛋白配体。我们发现朊病毒菌株以高度选择性和菌株特异性的方式相互作用，（1）没有相互作用，（2）杂交空斑形成，或（3）第二种菌株（干扰）阻断一种菌株。杂交菌斑在体内保持额外的传代，并且每个菌株似乎保持其原始构象特性，这表明一个菌株仅用作第二菌株聚集的支架。这些发现不仅加深了我们对朊病毒菌株相互作用的理解，而且直接证明了其他蛋白质聚集体混合物中可能发生的相互作用。
Various misfolded and aggregated neuronal proteins commonly coexist in neurodegenerative disease, but whether the proteins coaggregate and alter the disease pathogenesis is unclear. Here we used mixtures of distinct prion strains, which are believed to differ in conformation, to test the hypothesis that two different aggregates interact and change the disease in vivo. We tracked two prion strains in mice histopathologically and biochemically, as well as by spectral analysis of plaque-bound PTAA (polythiophene acetic acid), a conformation-sensitive fluorescent amyloid ligand. We found that prion strains interacted in a highly selective and strain-specific manner, with (1) no interaction, (2) hybrid plaque formation, or (3) blockage of one strain by a second (interference). The hybrid plaques were maintained on additional passage in vivo and each strain seemed to maintain its original conformational properties, suggesting that one strain served only as a scaffold for aggregation of the second strain. These findings not only further our understanding of prion strain interactions but also directly demonstrate interactions that may occur in other protein aggregate mixtures.