Human islet amyloid polypeptide (hIAPP), otherwise known as amylin, is a 37-residue peptide hormone which is reported to be a common factor in protein misfolding disorders such as type-2 diabetes mellitus, Alzheimer’s disease and Parkinson’s disease, due to deposition of insoluble hIAPP amyloid in the pancreas and brain. Multiple studies point to the importance of the peptide’s interaction with biological membranes and the cytotoxicity of hIAPP species. Here, we discuss the aggregation pathways of hIAPP amyloid fibril formation and focus on the complex interplay between membrane-mediated assembly of hIAPP and the associated mechanisms of membrane damage caused by the peptide species. Mitochondrial membranes, which are unique in their lipid composition, are proposed as prime targets for the early intracellular formation of hIAPP toxic entities. We suggest that future studies should include more physiologically-relevant and in-cell studies to allow a more accurate model of in vivo interactions. Finally, we underscore an urgent need for developing effective therapeutic strategies aimed at hindering hIAPP-phospholipid interactions.

人胰岛淀粉样多肽 (hIAPP)，也称为胰淀素，是一种含有 37 个残基的肽类激素，据报道是 2 型糖尿病、阿尔茨海默病和帕金森病等蛋白质错误折叠疾病的常见因素，这是由于胰腺和大脑中的不溶性 hIAPP 淀粉样蛋白。多项研究指出了肽与生物膜相互作用的重要性以及 hIAPP 物种的细胞毒性。在这里，我们讨论 hIAPP 淀粉样蛋白原纤维形成的聚集途径，并关注膜介导的 hIAPP 组装与肽类引起的膜损伤相关机制之间复杂的相互作用。线粒体膜具有独特的脂质组成，被提议作为 hIAPP 毒性实体早期细胞内形成的主要目标。体内相互作用。最后，我们强调迫切需要开发旨在阻碍 hIAPP-磷脂相互作用的有效治疗策略。