Protein fibrils in nature can enhance amyloid protein A amyloidosis in mice:: Cross-seeding as a disease mechanism
Protein fibrils in nature can enhance amyloid protein A amyloidosis in mice:: Cross-seeding as a disease mechanism
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DOI：
10.1073/pnas.0501814102
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发表时间：
2005-04-26
影响因子：
11.1
通讯作者：
Westermark, P
中科院分区：
文献类型：
--
作者：
Lundmark, K;Westermark, GT;Westermark, P
继发性淀粉样蛋白A (AA)，淀粉样变性是感染性和非感染性慢性炎症性疾病的并发症。AA构成不溶性原纤维，沉积于不同器官，是急性期蛋白血清AA的主要n端部分。目前尚不清楚为什么只有一些慢性炎症患者会发生AA淀粉样变。成核是淀粉样蛋白形成的一种被广泛接受的机制。预形成的淀粉样原纤维在体外淀粉样原纤维形成过程中起核作用，AA淀粉样原纤维和合成淀粉样原纤维在体内也可作为淀粉样原纤维形成的种子。除了淀粉样原纤维外，自然界中还有多种类似的非哺乳动物蛋白原纤维具有β -褶状结构。我们研究了三种天然存在的蛋白原纤维：家蚕丝、酿酒酵母Sup35和大肠杆菌curli。我们的研究结果表明，这些蛋白原纤维在小鼠实验性AA淀粉样变性中发挥淀粉样蛋白加速特性，提示这些环境因素可能是淀粉样蛋白发生的重要危险因素。
Secondary, or amyloid protein A (AA), amyloidosis is a complication of chronic inflammatory diseases, both infectious and noninfectious. AA constitutes the insoluble fibrils, which are deposited in different organs, and is a major N-terminal part of the acute phase protein serum AA. It is not known why only some patients with chronic inflammation develop AA amyloidosis. Nucleation is a widely accepted mechanism in amyloidogenesis. Preformed amyloid-like fibrils act as nuclei in amyloid fibril formation in vitro, and AA amyloid fibrils and synthetic amyloid-like fibrils also may serve as seed for fibril formation in vivo. In addition to amyloid fibrils, there is a variety of similar nonmammalian protein fibrils with beta-pleated structure in nature. We studied three such naturally occurring protein fibrils: silk from Bombyx mori, Sup35 from Saccharomyces cerevisiae, and curli from Escherichia coli. Our results show that these protein fibrils exert amyloid-accelerating properties in the murine experimental AA amyloidosis, suggesting that such environment factors may be important risk factors in amyloidogenesis.