The aggregation of peptides into amyloid fibrils is associated with several diseases, including Alzheimer’s and Parkinson’s disease. Because hydrophobic interactions often play an important role in amyloid formation, the presence of various hydrophobic or amphiphilic molecules, such as lipids, may influence the aggregation process. We have studied the effect of a fatty acid, linoleic acid, on the fibrillation process of the amyloid-forming model peptide NACore (GAVVTGVTAVA). NACore is a peptide fragment spanning residue 68–78 of the protein α-synuclein involved in Parkinson’s disease. Based primarily on circular dichroism measurements, we found that even a very small amount of linoleic acid can substantially inhibit the fibrillation of NACore. This inhibitory effect manifests itself through a prolongation of the lag phase of the peptide fibrillation. The effect is greatest when the fatty acid is present from the beginning of the process together with the monomeric peptide. Cryogenic transmission electron microscopy revealed the presence of nonfibrillar clusters among NACore fibrils formed in the presence of linoleic acid. We argue that the observed inhibitory effect on fibrillation is due to co-association of peptide oligomers and fatty acid aggregates at the early stage of the process. An important aspect of this mechanism is that it is nonmonomeric peptide structures that associate with the fatty acid aggregates. Similar mechanisms of action could be relevant in amyloid formation occurring in vivo, where the aggregation takes place in a lipid-rich environment.

肽聚集成淀粉样蛋白原纤维与多种疾病有关，包括阿尔茨海默病和帕金森病。由于疏水相互作用通常在淀粉样蛋白形成中起重要作用，因此各种疏水或两亲分子（如脂质）的存在可能会影响聚集过程。我们研究了脂肪酸亚油酸对淀粉样蛋白形成模型肽 NACore (GAVVTGVTAVA) 的纤颤过程的影响。NACore 是跨越蛋白质α的 68-78 残基的肽片段-与帕金森病有关的突触核蛋白。主要基于圆二色性测量，我们发现即使是非常少量的亚油酸也可以显着抑制 NACore 的原纤维化。这种抑制作用通过延长肽原纤化的滞后期而表现出来。当脂肪酸与单体肽一起存在于过程开始时，效果最大。低温透射电子显微镜显示在亚油酸存在下形成的 NACore 原纤维中存在非原纤维簇。我们认为，观察到的对纤颤的抑制作用是由于在该过程的早期阶段肽低聚物和脂肪酸聚集体的共同缔合。这种机制的一个重要方面是与脂肪酸聚集体相关的非单体肽结构。类似的作用机制可能与体内发生的淀粉样蛋白形成有关，其中聚集发生在富含脂质的环境中。