Issue 1, 2018

Tanshinones inhibit hIAPP aggregation, disaggregate preformed hIAPP fibrils, and protect cultured cells

Abstract

Misfolding and aggregation of amyloid peptides are the key pathological events in many neurodegenerative diseases. The development of effective inhibitors and drugs to prevent amyloid peptide aggregation is considered as an important therapeutic strategy for treating these diseases. We previously reported on tanshinones, ingredients from the Chinese herb Danshen (Salvia miltiorrhiza Bunge), as a potent inhibitor against amyloid-β1–42 (Aβ) aggregation and toxicity. Considering the common structural and aggregation features, and the correlation of type II diabetes (T2D) and Alzheimer's disease (AD), herein we examine the inhibition activity of two tanshinone I (TS1) and IIA (TS2) components on the aggregation and toxicity of hIAPP1–37 using combined experimental and computational approaches. Collective experimental data from ThT, CD, and AFM confirm that both tanshinones show comparable inhibition ability to reduce hIAPP aggregates by inhibiting the fibrillation process and changing the fibrillogenesis pathway, leading to the formation of some amorphous aggregates. More importantly, both tanshinones are capable of disassembling preformed hIAPP fibrils, but TS1 shows better potency in fibril dissembling than TS2. MTT and LDH assays also show that the tanshinones at very low concentrations of 5 μM can reduce the hIAPP-induced cell toxicity. Molecular dynamics (MD) simulations further reveal that both tanshinones preferentially bind to β-sheets to prevent lateral association of hIAPP aggregates and thus to inhibit fibril growth, explaining experimental observations. This work discovers that tanshinones act as common inhibitors to inhibit the aggregation of both hIAPP and Aβ, disaggregate preformed hIAPP and Aβ amyloid fibrils, and protect cells from hIAPP- and Aβ-induced toxicity, making them very promising agents against AD, T2D, and probably other amyloid-misfolding diseases.

Graphical abstract: Tanshinones inhibit hIAPP aggregation, disaggregate preformed hIAPP fibrils, and protect cultured cells

Article information

Article type
Paper
Submitted
22 Қыр. 2017
Accepted
17 Қар. 2017
First published
18 Қар. 2017

J. Mater. Chem. B, 2018,6, 56-67

Tanshinones inhibit hIAPP aggregation, disaggregate preformed hIAPP fibrils, and protect cultured cells

B. Ren, Y. Liu, Y. Zhang, M. Zhang, Y. Sun, G. Liang, J. Xu and J. Zheng, J. Mater. Chem. B, 2018, 6, 56 DOI: 10.1039/C7TB02538F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements