Computational and Experimental Approaches to Design Inhibitors of Amylin Aggregation

(E-pub Ahead of Print)

Author(s): Ammu Prasanna Kumar*, Sungmun Lee, Suryani Lukman*.

Journal Name: Current Drug Targets

Become EABM
Become Reviewer

Abstract:

Aggregates formed by amylin (a neuroendocrine peptide hormone secreted by pancreatic β-cells) are implicated in the pathogenesis of type 2 diabetes mellitus. To understand amylin’s aggregation mechanism and discover its inhibitory drugs, we have reviewed experimental and computational studies on amylin structures and inhibitors. We have also reviewed the role of amylin in other conditions including obesity and Alzheimer’s disease (AD), since effective therapeutics are still lacking for AD. Our results of text-mining over 3,000 amylin-related PubMed abstracts suggest the combined therapeutic potential of amylin with two other hormones: leptin and glucagon-like peptide-1, in obesity. In addition, our review suggests that targeting amylin aggregation can contribute to therapeutic efforts for AD. Our review provides some novel insights on amylin, particularly for the design of its aggregation inhibitors. We detail the potential inhibitors that have been studied hitherto. Amylin exhibits different characteristics depending 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 amylin-inhibitor complexes. Thus, we have critically reviewed the studies on amylin and its inhibitors, and suggested ways to design effective inhibitors of amylin aggregation.

Keywords: amylin, islet amyloid polypeptide, IAPP, aggregation inhibitors, type 2 diabetes therapy, Alzheimer`s disease therapy, conformation of amylin, literature review

Rights & PermissionsPrintExport Cite as

Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1389450120666190719164316
Price: $95