Come J H, Fraser P E, Lansbury P T
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5959-63. doi: 10.1073/pnas.90.13.5959.
The transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases characterized by amyloid formation in the brain. The major amyloid protein is the prion protein (PrP). PrP and the beta-amyloid protein of Alzheimer disease share a similar sequence that, in both cases, may be responsible for the initiation of protein aggregation in vivo. We report here that a peptide based on this sequence in PrP (PrP96-111M) forms amyloid fibrils. The existence of a kinetic barrier to amyloid formation by this peptide was demonstrated, suggesting that formation of an ordered nucleus is the rate-determining step for aggregation. Seeding was demonstrated to occur with PrP96-111M amyloid fibrils but not with amyloid fibrils of a related peptide. This effect is consistent with the proposal that the aggregation of PrP, which characterizes TSE, involves a nucleation event analogous to the seeding of a crystallization.
传染性海绵状脑病（TSEs）是一类神经退行性疾病，其特征是大脑中形成淀粉样蛋白。主要的淀粉样蛋白是朊病毒蛋白（PrP）。PrP与阿尔茨海默病的β-淀粉样蛋白具有相似的序列，在这两种情况下，该序列可能是体内蛋白质聚集起始的原因。我们在此报告，基于PrP中该序列的一种肽（PrP96 - 111M）形成了淀粉样纤维。已证明该肽形成淀粉样蛋白存在动力学障碍，这表明形成有序核是聚集的速率决定步骤。已证明PrP96 - 111M淀粉样纤维会发生成核作用，而相关肽的淀粉样纤维则不会。这种效应与以下观点一致，即作为TSE特征的PrP聚集涉及类似于结晶成核的成核事件。
