Sakalauskas Andrius, Ziaunys Mantas, Smirnovas Vytautas
Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
PeerJ. 2019 Dec 10;7:e8208. doi: 10.7717/peerj.8208. eCollection 2019.
Protein aggregation into highly structured fibrils has long been associated with several neurodegenerative disorders, such as Alzheimer's or Parkinson's disease. Polymorphism of amyloid fibrils increases the complexity of disease mechanisms and may be one of the reasons for the slow progress in drug research. Here we report protein concentration as another factor leading to polymorphism of insulin amyloid fibrils. Moreover, our data suggests that insulin amyloid conformation can self-replicate only via elongation, while seed-induced nucleation will lead to environment-defined conformation of fibrils. As similar observations were already described for a couple of other amyloid proteins, we suggest it to be a generic mechanism for self-replication of different amyloid fibril conformations.
蛋白质聚集成高度结构化的纤维长期以来一直与几种神经退行性疾病相关，如阿尔茨海默病或帕金森病。淀粉样纤维的多态性增加了疾病机制的复杂性，可能是药物研究进展缓慢的原因之一。在此，我们报告蛋白质浓度是导致胰岛素淀粉样纤维多态性的另一个因素。此外，我们的数据表明胰岛素淀粉样构象只能通过延长进行自我复制，而种子诱导的成核将导致纤维的环境定义构象。由于已经对其他几种淀粉样蛋白进行了类似的观察，我们认为这是不同淀粉样纤维构象自我复制的通用机制。
