Transmissibility of systemic amyloidosis by a prion-like mechanism
Transmissibility of systemic amyloidosis by a prion-like mechanism
复制标题
DOI：
10.1073/pnas.092205999
复制
发表时间：
2002-05-14
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
从淀粉样多肽产生淀粉样纤维是通过在体外通过将蛋白质溶液与预形成的纤维播撒而启动的依赖于核的过程来产生淀粉样纤维的。这一现象在体内的证据是，当动物除了给予炎症刺激外，静脉注射淀粉样蛋白A(AA)显著加速了小鼠的淀粉样变性。注射从AA淀粉样蛋白负载的小鼠组织中提取的蛋白质。到目前为止，这种“淀粉样蛋白增强因子”(AEF)的化学性质还没有明确的确定。在此，我们报道了从硝酸银诱导的AA淀粉样变性小鼠的脾中提取的AEF的活性成分被明确地确定为AA纤维本身。此外，我们证明了这种材料是非常有效的，在剂量<；1纳克，它保持其生物活性在相当长的时间。值得注意的是，AEF在口服时也有效。我们的研究提供了证据，证明再生障碍性贫血和其他形式的淀粉样变性是可传播的疾病，类似于普里恩相关疾病。
The generation of amyloid fibrils from an amyloidogenic polypeptide occurs by a nucleation-dependent process initiated in vitro by seeding the protein solution with preformed fibrils. This phenomenon is evidenced in vivo by the fact that amyloid protein A (AA) amyloidosis in mice is markedly accelerated when the animals are given, in addition to an inflammatory stimulus, an i.v. injection of protein extracted from AA amyloid-laden mouse tissue. Heretofore, the chemical nature of this "amyloid enhancing factor" (AEF) has not been definitively identified. Here we report that the active principle of AEF extracted from the spleen of mice with silver nitrate-induced AA amyloidosis was identified unequivocally as the AA fibril itself. Further, we demonstrated that this material was extremely potent, being active in doses < 1 ng, and that it retained its biologic activity over a considerable length of time. Notably, the AEF was also effective when administered orally. Our studies have provided evidence that AA and perhaps other forms of amyloidosis are transmissible diseases, akin to the prion-associated disorders.