期刊
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
卷 175, 期 -, 页码 49-62出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbiomolbio.2022.09.001
关键词
Insulin; Fibrillation; Natural compounds; Polyphenols; Nanoparticles; Inhibition mechanisms; Inhibition strategies
资金
- University of Tehran
- Tarbiat Modares University
- Iran National Science Foundation (INSF)
- Iran National Elites Foundation
- National Institute for Medical Research Development (NIMAD)
- UNESCO Chair on Interdisciplinary Research in Diabetes
- University of Tehran
- Tarbiat Modares University
- Iran National Science Foundation (INSF)
- Iran National Elites Foundation
- National Institute for Medical Research Development (NIMAD)
- UNESCO Chair on Interdisciplinary Research in Diabetes
Insulin and its homologous play a crucial role in diabetic patients' treatment and can form amyloid-like fibrils. Therefore, understanding the fibrillation mechanism and developing effective inhibitors are important in the pharmaceutical industry. There are various inhibitors that can stabilize the native structure of the protein, inhibit formation of partially folded species, hinder different steps in the fibrillation process, and even dissociate pre-existing fibrils.
Insulin and its homologous are the most utilized protein drugs due to their role in diabetic patients' treatment. Insulin forms amyloid-like fibrils in vivo at the injection site. Therefore, the study of its fibrillation mechanism and designing efficient inhibitors have high importance in the pharmaceutical industry. Insulin fibrils are formed at both acidic and neutral pH in vitro. Overall, this process involves the dissociation of hexameric form to monomeric, partially dissociating the native monomeric form, nuclei formation, and finally converting oligomers to large ordered aggregates. Intermediate and terminal species are different pathologically. This review is focused on the research works dedicated to the inhibition of insulin fibril formation. The inhibitors include various polyphenols, natural compounds, nanoparticles, and synthetic chemicals/peptides, as well as the clas-sification of inhibitors targets concerning protein fibrillation. Although most inhibitors stabilize the native structure of the protein and prevent the formation of partially folded species, there are other inhibitors that hinder other steps in the course of fibrillation. Also, several inhibitors were able to dissociate the pre-existing fibrils. Finding inhibition strategies could be beneficial for developing new inhibitors that are more efficient and can block the amyloid pathway in a specific desired stage.
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