Physical and toxicological profiles of human IAPP amyloids and plaques

作     者：Aleksandr Kakinen Yunxiang Sun Ibrahim Javed Ava Faridi Emily H.Pilkington Pouya Faridi Anthony W.Purcell Ruhong Zhou Feng Ding Sijie Lin Pu Chun Ke Thomas P.Davis 

作者机构：ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Monash Institute of Pharmaceutical Sciences Monash University Department of Physics and Astronomy Clemson University College of Environmental Science and Engineering Shanghai Institute of Pollution Control and Ecological Security Biomedical Multidisciplinary Innovation Research Institute Shanghai East Hospital Tongji University Infection and Immunity Program & Department of Biochemistry and Molecular Biology Biomedicine Discovery Institute Monash University IBM Thomas J.Watson Research Center Department of Chemistry Columbia University 

出 版 物：《Science Bulletin》 (科学通报（英文版）)

年 卷 期：2019年第64卷第1期

页      面：26-35页

核心收录：

学科分类：07[理学] 08[工学] 

基　　金：supported by ARC Project CE140100036 (Davis), NSF CAREER CBET-1553945 (Ding), NIH MIRA R35GM119691 (Ding) and Monash Institute of Pharmaceutical Sciences (Ke) Purcell is supported by a Principal Research Fellowship from the Australian NHMRC Pilkington acknowledges an Australian Government Research Training Program (RTP) Scholarship Javed acknowledges Monash International Postgraduate Research Scholarship 

主　　题：IAPP Amyloid Plaque Self assembly Toxicity 

摘      要：Although much has been learned about the fibrillization kinetics, structure and toxicity of amyloid proteins, the properties of amyloid fibrils beyond the saturation phase are often perceived as chemically and biologically inert, despite evidence suggesting otherwise. To fill this knowledge gap, we examined the physical and biological characteristics of human islet amyloid polypeptide(IAPP) fibrils that were aged up to two months. Not only did aging decrease the toxicity of IAPP fibrils, but the fibrils also sequestered fresh IAPP and suppressed their toxicity in an embryonic zebrafish model. The mechanical properties of IAPP fibrils in different aging stages were probed by atomic force microscopy and sonication, which displayed comparable stiffness but age-dependent fragmentation, followed by self-assembly of such fragments into the largest lamellar amyloid structures reported to date. The dynamic structural and toxicity profiles of amyloid fibrils and plaques suggest that they play active, long-term roles in cell degeneration and may be a therapeutic target for amyloid diseases.