Type 2 diabetes (T2D) is a common protein misfolding disease (PMD), and its pathogenesis is considered to be tightly associated with the aggregation of the disease-causative hIAPP (or amylin). Numerous studies have shown a possible pathological link between hIAPP aggregation and β-cell death; thus, different-level strategies from basic research to clinical bench applications have been applied to discover and design different types of inhibitors for preventing hIAPP aggregation and toxicity. This review surveys recent and important advances of hIAPP aggregation inhibitors in the context of amyloid aggregation, toxicity, and inhibition. Many hIAPP inhibitors have been explored to exert different inhibitory functions on hIAPP aggregation via different pathways. A further overview of molecular simulations of inhibitor–hIAPP systems highlights some consensus binding sequences and structures of hIAPP for different inhibitors, which provide molecular insights into well-defined binding targets and binding-induced inhibition mechanisms for structural-based design of hIAPP inhibitors. In a broader view, while anti-aggregation inhibitors hold substantial promise in the prevention of PMDs, many challenges still remain and need to be addressed for advancing our fundamental understanding of amyloid aggregation and practical design of clinically relevant inhibitors to treat PMDs.

中文翻译：

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人胰岛淀粉样多肽抑制剂的介绍和基本原理

2型糖尿病（T2D）是一种常见的蛋白质错误折叠疾病（PMD），其发病机制被认为与致病的hIAPP（或胰淀素）的聚集密切相关。大量研究表明 hIAPP 聚集和 β 细胞死亡之间可能存在病理联系。因此，从基础研究到临床试验应用的不同层次的策略已被应用于发现和设计不同类型的抑制剂，以防止 hIAPP 聚集和毒性。本综述调查了 hIAPP 聚集抑制剂在淀粉样蛋白聚集、毒性和抑制方面的最新重要进展。许多 hIAPP 抑制剂已被探索通过不同的途径对 hIAPP 聚集发挥不同的抑制功能。对抑制剂-hIAPP系统的分子模拟的进一步概述突出了不同抑制剂的hIAPP的一些共有结合序列和结构，这为基于结构的hIAPP抑制剂设计提供了明确的结合靶点和结合诱导的抑制机制的分子见解。从更广泛的角度来看，虽然抗聚集抑制剂在预防 PMD 方面具有很大的前景，但仍然存在许多挑战，需要解决许多挑战，以促进我们对淀粉样蛋白聚集的基本理解和临床相关抑制剂治疗 PMD 的实用设计。