计算和实验方法设计的胰岛淀粉样多肽聚集抑制剂

Title:Computational and Experimental Approaches to Design Inhibitors of Amylin Aggregation

Volume: 20 Issue: 16

关键词: 胰岛淀粉样多肽，胰岛淀粉样多肽，IAPP，聚集抑制剂，2型糖尿病治疗，阿尔茨海默氏病治疗，胰岛淀粉样多肽的构象，文献综述。

摘要: Amylin is a neuroendocrine peptide hormone secreted by pancreatic ß-cells; however, amylin is toxic to ß-cells when it is aggregated in type 2 diabetes mellitus (T2DM). It is important to understand amylin’s structures and aggregation mechanism for the discovery and design of effective drugs to inhibit amylin aggregation. In this review, we investigated experimental and computational studies on amylin structures and inhibitors. Our review provides some novel insights into amylin, particularly for the design of its aggregation inhibitors to treat T2DM. We detailed the potential inhibitors that have been studied hitherto and highlighted the neglected need to consider different amylin attributes that depend on the presence/absence of physiologically relevant conditions, such as membranes. These conditions and the experimental methods can greatly influence the results of studies on amylininhibitor complexes. Text-mining over 3,000 amylin-related PubMed abstracts suggests the combined therapeutic potential of amylin with leptin and glucagon-like peptide-1, which are two key hormones in obesity. The results also suggest that targeting amylin aggregation can contribute to therapeutic efforts for Alzheimer’s disease (AD). Therefore, we have also reviewed the role of amylin in other conditions including obesity and AD. Finally, we provided insights for designing inhibitors of different types (small molecules, proteins, peptides/mimetics, metal ions) to inhibit amylin aggregation.

Cite this article as:

Computational and Experimental Approaches to Design Inhibitors of Amylin Aggregation, Current Drug Targets 2019; 20 (16) . https://dx.doi.org/10.2174/1389450120666190719164316