Gajdusek D C
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Mol Neurobiol. 1994 Feb;8(1):1-13. doi: 10.1007/BF02778003.
The unconventional viruses of the transmissible subacute spongiform encephalopathies (kuru-CJD-GSS-FFI-scrapie-BSE) are nucleants spontaneously generated from host precursor proteins altered to beta-pleated sheet configuration that polymerize into insoluble infectious amyloid fibrils. The de novo conversion to infectious amyloids is facilitated or accelerated by many different point mutations causing amino acid changes, a stop codon, or octapeptide inserts that increase the likelihood of spontaneous conversion to infectious configuration by many orders of magnitude. Similar nucleating induction of configurational change to amyloid probably occurs in other amyloidoses of brain and in systemic amyloidoses. Thus, all amyloids, particularly so-called fibrillar amyloid enhancing factors, may be considered to be infectious scrapie-like agents. These events probably occur extracellularly, thus we are attempting to reproduce them in vitro, even from synthetic polypeptides.
可传播性亚急性海绵状脑病（库鲁病 - 克雅氏病 - 格斯特曼综合征 - 致死性家族性失眠症 - 羊瘙痒症 - 疯牛病）的非常规病毒是由宿主前体蛋白自发产生的核蛋白，这些前体蛋白转变为β - 折叠结构，聚合成不溶性感染性淀粉样纤维。许多不同的点突变导致氨基酸变化、终止密码子或八肽插入，促进或加速了向感染性淀粉样蛋白的从头转化，这些突变使自发转化为感染性构型的可能性增加了许多个数量级。类似的诱导构型转变为淀粉样蛋白的成核作用可能发生在其他脑淀粉样变性和系统性淀粉样变性中。因此，所有淀粉样蛋白，特别是所谓的纤维状淀粉样增强因子，都可被视为感染性羊瘙痒症样因子。这些事件可能发生在细胞外，因此我们正试图在体外重现它们，甚至从合成多肽开始。
